Ignite Creation Date:
2025-12-24 @ 3:37 PM
Ignite Modification Date:
2026-04-10 @ 2:11 AM
Study NCT ID:
NCT00662792
Status:
COMPLETED
Last Update Posted:
2022-06-28
First Post:
2008-04-17
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Efficacy and Safety Comparison of Tiotropium Daily + Salmeterol Daily or Twice Daily Versus Tiotropium Daily in Patients With COPD
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D029424', 'term': 'Pulmonary Disease, Chronic Obstructive'}], 'ancestors': [{'id': 'D008173', 'term': 'Lung Diseases, Obstructive'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000069447', 'term': 'Tiotropium Bromide'}, {'id': 'D000068299', 'term': 'Salmeterol Xinafoate'}], 'ancestors': [{'id': 'D012602', 'term': 'Scopolamine Derivatives'}, {'id': 'D014326', 'term': 'Tropanes'}, {'id': 'D053961', 'term': 'Azabicyclo Compounds'}, {'id': 'D001372', 'term': 'Aza Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D019086', 'term': 'Bridged Bicyclo Compounds, Heterocyclic'}, {'id': 'D006572', 'term': 'Heterocyclic Compounds, Bridged-Ring'}, {'id': 'D000420', 'term': 'Albuterol'}, {'id': 'D004983', 'term': 'Ethanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D010627', 'term': 'Phenethylamines'}, {'id': 'D005021', 'term': 'Ethylamines'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clintriage.rdg@boehringer-ingelheim.com', 'phone': '1-800-243-0127', 'title': 'Boehringer Ingelheim, Call Center', 'organization': 'Boehringer Ingelheim'}, 'certainAgreement': {'otherDetails': "Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.", 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'From first drug administration until last drug administration (average duration of 42 days) + 30 days, up to 91 days for T+S_PE, up to 98 days for Tio18GEL, up 89 days for Salm50DPI and up to 113 days for T18GEL+S_DPI.', 'description': 'Treated Set (TS): All randomised patients who took at least one dose of study medication.', 'eventGroups': [{'id': 'EG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.', 'otherNumAtRisk': 132, 'deathsNumAtRisk': 132, 'otherNumAffected': 14, 'seriousNumAtRisk': 132, 'deathsNumAffected': 0, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': '18 µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.', 'otherNumAtRisk': 135, 'deathsNumAtRisk': 135, 'otherNumAffected': 15, 'seriousNumAtRisk': 135, 'deathsNumAffected': 1, 'seriousNumAffected': 7}, {'id': 'EG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.', 'otherNumAtRisk': 137, 'deathsNumAtRisk': 137, 'otherNumAffected': 14, 'seriousNumAtRisk': 137, 'deathsNumAffected': 0, 'seriousNumAffected': 4}, {'id': 'EG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.', 'otherNumAtRisk': 132, 'deathsNumAtRisk': 132, 'otherNumAffected': 11, 'seriousNumAtRisk': 132, 'deathsNumAffected': 0, 'seriousNumAffected': 2}, {'id': 'EG004', 'title': 'Total Treated', 'description': 'All patients who received at least one dose of study medication.', 'otherNumAtRisk': 146, 'deathsNumAtRisk': 146, 'otherNumAffected': 47, 'seriousNumAtRisk': 146, 'deathsNumAffected': 1, 'seriousNumAffected': 13}], 'otherEvents': [{'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 9}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 9}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 7}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 6}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 27}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Chronic obstructive pulmonary disease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 7}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 3}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 18}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Dyspnoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 2}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 8}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}], 'seriousEvents': [{'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 3}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Mastoiditis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Meningitis pneumococcal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Pneumococcal infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Colon cancer', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Hepatic neoplasm malignant', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Prostate cancer', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Haemorrhagic anaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Intracranial aneurysm', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Subarachnoid haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Cardiac failure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Congestive cardiomyopathy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Right ventricular failure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Chronic obstructive pulmonary disease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 4}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Dyspnoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Diarrhoea haemorrhagic', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Diverticulum intestinal haemorrhagic', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Gastrointestinal haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Intestinal haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Cholecystitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}, {'term': 'Cholelithiasis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 132, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 135, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 137, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 132, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 12.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 - 12 Hours (AUC0-12)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18 µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.187', 'spread': '0.026', 'groupId': 'OG000'}, {'value': '0.117', 'spread': '0.026', 'groupId': 'OG001'}, {'value': '0.057', 'spread': '0.026', 'groupId': 'OG002'}, {'value': '0.211', 'spread': '0.026', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.130', 'ciLowerLimit': '0.102', 'ciUpperLimit': '0.158', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.014', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'H1: Superiority of FDC Tiotropium/Salmeterol (T+S\\_PE) vs. salmeterol (Salm50DPI) for FEV1 AUC0-12', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient with centre, treatment, and period.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.070', 'ciLowerLimit': '0.042', 'ciUpperLimit': '0.097', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.014', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'H1: Superiority of FDC Tiotropium/Salmeterol (T+S\\_PE) vs Tiotropium (Tio18GEL) for FEV1 AUC0- 12', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient with centre, treatment, and period.\n\nα = 0.025 one-sided'}, {'pValue': '0.0914', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.024', 'ciLowerLimit': '-0.052', 'ciUpperLimit': '0.004', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.014', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'The Tiotropium free combination (T18GEL+S\\_DPI) was included in order to characterise this treatment in comparison with the FDC Tiotropium/Salmeterol (T+S\\_PE). No formal hypotheses were defined.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Analysis of variance with terms for centre, patient with centre, treatment, and period. α = 0.025 one-sided'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment.', 'description': 'FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 12 h (FEV1 AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FEV1 AUC0-12h response is defined as the change from baseline:\n\nFEV1 AUC0-12h response = FEV1 AUC0-12h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter (L)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'PRIMARY', 'title': 'Response in Forced Expiratory Volume in Second (FEV1) Area Under the Curve From 12 - 24 Hours (AUC12 -24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18 µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.068', 'spread': '0.025', 'groupId': 'OG000'}, {'value': '0.003', 'spread': '0.025', 'groupId': 'OG001'}, {'value': '0.003', 'spread': '0.025', 'groupId': 'OG002'}, {'value': '0.124', 'spread': '0.025', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.064', 'ciLowerLimit': '0.036', 'ciUpperLimit': '0.093', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.015', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'H1: Non-Inferiority of FDC Tiotropium/Salmeterol (T+S\\_PE) vs. Salmeterol (Salm50DPI) for FEV1AUC12-24', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'NON_INFERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient with centre, treatment, and period.\n\nα = 0.025 one-sided', 'nonInferiorityComment': 'The non-inferiority margin for FEV1 endpoints was defined as d=0.050 L.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.064', 'ciLowerLimit': '0.036', 'ciUpperLimit': '0.093', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.015', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'H1: Non-inferiority of FDC Tiotropium/Salmeterol (T+S\\_PE) vs. Tiotropium (TIO18GEL) of FEV1AUC12-24', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'NON_INFERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient with centre, treatment, and period.\n\nα = 0.025 one-sided', 'nonInferiorityComment': 'The non-inferiority margin for FEV1 endpoints was defined as d=0.050 L.'}, {'pValue': '0.0001', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.057', 'ciLowerLimit': '-0.086', 'ciUpperLimit': '-0.028', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.015', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'The Tiotropium free combination (T18GEL+S\\_DPI) was included in order to characterise this treatment in comparison with the FDC Tiotropium/Salmeterol (T+S\\_PE). No formal hypotheses were defined.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Analysis of variance with terms for centre, patient with centre, treatment, and period.\n\nα = 0.025 one-sided'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'The FEV1 AUC was defined as the area under the FEV1 curve (AUC) normalised for time. It was calculated from time 12 to 24 h (FEV1 AUC12-24), using the trapezoidal rule divided by the corresponding duration (i.e. 12 h) to give the results in L.\n\nAUC12-24h response is defined as the change from baseline:\n\nFEV1 AUC12-24h response = FEV1 AUC12-24h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit (Visit 2) just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter (L)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'PRIMARY', 'title': 'Response in Peak Forced Expiratory Volume in 1 Second (FEV1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.296', 'spread': '0.026', 'groupId': 'OG000'}, {'value': '0.229', 'spread': '0.026', 'groupId': 'OG001'}, {'value': '0.161', 'spread': '0.026', 'groupId': 'OG002'}, {'value': '0.320', 'spread': '0.026', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.134', 'ciLowerLimit': '0.102', 'ciUpperLimit': '0.166', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.016', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'H1: Superiority of FDC Tiotropium/Salmeterol (T+S\\_PE) vs. Salmeterol (Salm50DPI) of Peak FEV1', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient with centre, treatment, and period.\n\nα = 0.025 one-sided'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.066', 'ciLowerLimit': '0.034', 'ciUpperLimit': '0.098', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.016', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'H1: Superiority of FDC Tiotropium/Salmeterol (T+S\\_PE) vs. Tiotropium (TIO18GEL) of PeakFEV1.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of with terms for centre, patient with centre, treatment, and period. α = 0.025 one-sided'}, {'pValue': '0.1093', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.026', 'ciLowerLimit': '-0.058', 'ciUpperLimit': '0.006', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.016', 'estimateComment': '(T+S\\_PE) - (T18GEL+S\\_DPI)', 'groupDescription': 'The Tiotropium free combination (T18GEL+S\\_DPI) was included in order to characterise this treatment in comparison with the FDC Tiotropium/Salmeterol (T+S\\_PE). No formal hypotheses were defined.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Analysis of variance with terms for centre, patient with centre, treatment, and period.\n\nα = 0.025 one-sided'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and within 3 hours post-morning dose after 6 weeks of treatment.', 'description': 'Peak FEV1 was defined as the highest FEV1 reading observed within 3 hours after inhalation of the last morning dose of each randomized treatment. Peak FEV1 response is defined as change from baseline:\n\nPeak FEV1 response = Peak FEV1 - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'PRIMARY', 'title': 'Response in Trough Forced Expiratory Volume in 1 Second (FEV1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.062', 'spread': '0.024', 'groupId': 'OG000'}, {'value': '0.032', 'spread': '0.024', 'groupId': 'OG001'}, {'value': '0.003', 'spread': '0.024', 'groupId': 'OG002'}, {'value': '0.097', 'spread': '0.024', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.0008', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Differences of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.058', 'ciLowerLimit': '0.024', 'ciUpperLimit': '0.092', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.017', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'H1: Non-inferiority of FDC Tiotropium/Salmeterol (T+S\\_PE) vs. Salmeterol (Salm50DPI) of trough FEV1', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'NON_INFERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient with centre, treatment, and period.\n\nα = 0.025 one-sided', 'nonInferiorityComment': 'The non-inferiority margin for FEV1 endpoints was defined as d=0.050 L.'}, {'pValue': '0.0857', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.029', 'ciLowerLimit': '-0.004', 'ciUpperLimit': '0.063', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.017', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'H1: Non-inferiority of FDC Tiotropium/Salmeterol (T+S\\_PE) vs. Tiotropium (TIO18GEL) of trough FEV1', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'NON_INFERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient with centre, treatment, and period.\n\nα = 0.025 one-sided', 'nonInferiorityComment': 'The non-inferiority margin for FEV1 endpoints was defined as a delta of 0.050 L.'}, {'pValue': '0.0317', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.037', 'ciLowerLimit': '-0.071', 'ciUpperLimit': '-0.003', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.017', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'The Tiotropium free combination (T18GEL+S\\_DPI) was included in order to characterise this treatment in comparison with the FDC Tiotropium/Salmeterol (T+S\\_PE). No formal hypotheses were defined.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'OTHER', 'statisticalComment': 'Analysis of variance with terms for centre, patient with centre, treatment, and period.\n\nα = 0.025 one-sided'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.', 'description': 'Trough FEV1 is determined at the end of each treatment period and is defined as the pre-dose FEV1 measured just prior to the last administration of the morning dose of randomized treatment.\n\nTrough FEV1 response is defined as the change from baseline:\n\nTrough FEV1 response = Trough FEV1 - FEV1 (Baseline) The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0-24 Hours (AUC0-24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.128', 'spread': '0.025', 'groupId': 'OG000'}, {'value': '0.060', 'spread': '0.025', 'groupId': 'OG001'}, {'value': '0.030', 'spread': '0.025', 'groupId': 'OG002'}, {'value': '0.167', 'spread': '0.025', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.097', 'ciLowerLimit': '0.071', 'ciUpperLimit': '0.124', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.014', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'H1: Superiority of FDC Tiotropium/Salmeterol (T+S\\_PE) vs. salmeterol (Salm50DPI) for FEV1 AUC0-24', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted mean difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.067', 'ciLowerLimit': '0.041', 'ciUpperLimit': '0.093', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.013', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'H1: Superiority of FDC Tiotropium/Salmeterol (T+S\\_PE) vs. Tiotropium (TIO18GEL) for FEV1 AUC24', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided'}, {'pValue': '0.0029', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.041', 'ciLowerLimit': '-0.067', 'ciUpperLimit': '-0.014', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.014', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 24 h (FEV1 AUC0-24), using the trapezoidal rule divided by the corresponding duration (24 h) to give the results in liter (L). FEV1 AUC0-24h response is defined as the change from baseline:\n\nFEV1 AUC0-24h response = FEV1 AUC0-24h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 to 12 Hours (AUC0-12)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.337', 'spread': '0.047', 'groupId': 'OG000'}, {'value': '0.253', 'spread': '0.047', 'groupId': 'OG001'}, {'value': '0.160', 'spread': '0.048', 'groupId': 'OG002'}, {'value': '0.381', 'spread': '0.047', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.0010', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.083', 'ciLowerLimit': '0.034', 'ciUpperLimit': '0.132', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.025', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.176', 'ciLowerLimit': '0.127', 'ciUpperLimit': '0.226', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.025', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0757', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.045', 'ciLowerLimit': '-0.095', 'ciUpperLimit': '0.005', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.025', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment.', 'description': 'FVC AUC was defined as the area under the FVC curve normalized for time. It was calculated from time 0 to 12 h (FVC AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FVC AUC0-12h response is defined as the change from baseline:\n\nFVC AUC0-12h response = FVC AUC0-12h - FVC (Baseline). The baseline value for FVC based parameters is defined as the pre-dose FVC measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Forced Vital Capacity (FVC) Area Under the Curve From 12 to 24 Hours (AUC12-24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.163', 'spread': '0.048', 'groupId': 'OG000'}, {'value': '0.076', 'spread': '0.048', 'groupId': 'OG001'}, {'value': '0.043', 'spread': '0.048', 'groupId': 'OG002'}, {'value': '0.245', 'spread': '0.048', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.0015', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.085', 'ciLowerLimit': '0.033', 'ciUpperLimit': '0.137', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.027', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.118', 'ciLowerLimit': '0.066', 'ciUpperLimit': '0.171', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.027', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0017', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.085', 'ciLowerLimit': '-0.138', 'ciUpperLimit': '-0.032', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.027', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 10, 11 and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'The FVC AUC was defined as the area under the FVC curve (AUC) normalised for time. It was calculated from time 12 to 24 h (FVC AUC12-24), using the trapezoidal rule divided by the corresponding duration (i.e. 12 h) to give the results in L.\n\nAUC12-24h response is defined as the change from baseline:\n\nFVC AUC12-24h response = FVC AUC12-24h - FVC (Baseline). The FVC baseline value is defined as the pre-dose FVC measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 - 24 Hours (AUC0-24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.250', 'spread': '0.046', 'groupId': 'OG000'}, {'value': '0.165', 'spread': '0.046', 'groupId': 'OG001'}, {'value': '0.102', 'spread': '0.046', 'groupId': 'OG002'}, {'value': '0.313', 'spread': '0.046', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.0005', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.084', 'ciLowerLimit': '0.037', 'ciUpperLimit': '0.131', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.024', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.147', 'ciLowerLimit': '0.100', 'ciUpperLimit': '0.194', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.024', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0074', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.065', 'ciLowerLimit': '-0.113', 'ciUpperLimit': '-0.018', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.024', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hour after inhalation the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'The FVC AUC was defined as the area under the FVC curve (AUC) normalised for time. It was calculated from time 0 to 24 h (FVC AUC0-24), using the trapezoidal rule divided by the corresponding duration (i.e. 24 h) to give the results in L. AUC response was defined as the change from the baseline FVC; baseline was defined as the FVC measured on randomisation visit. Mean is adjusted mean.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Peak Forced Vital Capacity (FVC)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.502', 'spread': '0.049', 'groupId': 'OG000'}, {'value': '0.449', 'spread': '0.049', 'groupId': 'OG001'}, {'value': '0.359', 'spread': '0.050', 'groupId': 'OG002'}, {'value': '0.556', 'spread': '0.049', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.0898', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Differences of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.051', 'ciLowerLimit': '-0.008', 'ciUpperLimit': '0.109', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.030', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.142', 'ciLowerLimit': '0.083', 'ciUpperLimit': '0.201', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.030', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0601', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.057', 'ciLowerLimit': '-0.116', 'ciUpperLimit': '0.002', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.030', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and within 3 hours post-morning dose after 6 weeks of treatment.', 'description': 'Peak FEV1 was defined as the highest FEV1 reading observed within 3 hours after inhalation of the last morning dose of each randomized treatment.\n\nPeak FEV1 response is defined as change from baseline:\n\nPeak FEV1 response = Peak FEV1 - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analyzed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Trough Forced Vital Capacity (FVC)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '0.139', 'spread': '0.047', 'groupId': 'OG000'}, {'value': '0.165', 'spread': '0.047', 'groupId': 'OG001'}, {'value': '0.095', 'spread': '0.048', 'groupId': 'OG002'}, {'value': '0.229', 'spread': '0.047', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.3652', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.028', 'ciLowerLimit': '-0.089', 'ciUpperLimit': '0.033', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.031', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.1816', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.042', 'ciLowerLimit': '-0.020', 'ciUpperLimit': '0.103', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.031', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0026', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.095', 'ciLowerLimit': '-0.157', 'ciUpperLimit': '-0.033', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.031', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.', 'description': 'Trough FVC1 is determined at the end of each 6-week treatment period and is defined as the pre-dose FVC1 measured just prior to the last administration of the morning dose of randomized treatment.\n\nTrough FVC1 response is defined as the change from baseline:\n\nTrough FVC1 response = Trough FVC1 - FVC1 (Baseline) The FVC1 baseline value is defined as the pre-dose FVC1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve Form 0 to 12 Hours (AUC0-12)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '34.5', 'spread': '5.2', 'groupId': 'OG000'}, {'value': '22.5', 'spread': '5.2', 'groupId': 'OG001'}, {'value': '10.2', 'spread': '5.2', 'groupId': 'OG002'}, {'value': '37.8', 'spread': '5.1', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '<.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '11.8', 'ciLowerLimit': '6.9', 'ciUpperLimit': '16.8', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.5', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '24.2', 'ciLowerLimit': '19.2', 'ciUpperLimit': '29.2', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.5', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.1804', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-3.4', 'ciLowerLimit': '-8.5', 'ciUpperLimit': '1.6', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.6', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 10 minutes (min) prior and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment.', 'description': 'PEF(L/min) AUC0-12(h) response is defined as the change from baseline. AUC0-12(h) was calculated as the area under the curve from 0 to 12 hours using the trapezoidal rule, divided by the full duration (12 hours) to report in liter/minutes.\n\nPEF AUC0-12h response = PEF AUC0-12h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter/minutes (L/min)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 12 to 24 Hours (AUC12-24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '7.3', 'spread': '5.1', 'groupId': 'OG000'}, {'value': '-1.3', 'spread': '5.1', 'groupId': 'OG001'}, {'value': '-3.4', 'spread': '5.1', 'groupId': 'OG002'}, {'value': '20.0', 'spread': '5.1', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.0008', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '8.5', 'ciLowerLimit': '3.5', 'ciUpperLimit': '13.4', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.5', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '10.6', 'ciLowerLimit': '5.6', 'ciUpperLimit': '15.5', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.5', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-12.9', 'ciLowerLimit': '-17.9', 'ciUpperLimit': '-8.0', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.5', 'estimateComment': '(T+S\\_PE) - (T18GEL+S\\_DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 10 minutes (min) prior and 30 min, 60 min, 2, 10, 11 and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'PEF(L/min) AUC12-24(h) response is defined as the change from baseline. AUC12-24(h) was calculated as the area under the curve from 12 to 24 hours using the trapezoidal rule, divided by the full duration (12 hours) to report in liter/minutes.\n\nPEF AUC12-24h response = PEF AUC12-24h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter/minutes (L/min)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 0 to 24 Hours (AUC0-24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '20.8', 'spread': '5.0', 'groupId': 'OG000'}, {'value': '10.6', 'spread': '5.0', 'groupId': 'OG001'}, {'value': '3.4', 'spread': '5.0', 'groupId': 'OG002'}, {'value': '28.9', 'spread': '5.0', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '<.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '10.1', 'ciLowerLimit': '5.7', 'ciUpperLimit': '14.6', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.3', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '17.4', 'ciLowerLimit': '12.9', 'ciUpperLimit': '21.9', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.3', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0004', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-8.2', 'ciLowerLimit': '-12.7', 'ciUpperLimit': '-3.7', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.3', 'estimateComment': '(T+S\\_PE) - (T18GEL+S\\_DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'PEF(L/min) AUC0-24(h) response is defined as the change from baseline. AUC0-24(h) was calculated as the area under the curve from 0 to 24 hours using the trapezoidal rule, divided by the full duration (24 hours) to report in liter/minutes.\n\nPEF AUC0-24h response = PEF AUC0-24h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter/minutes (L/min)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Peak PEF (Peak Expiratory Flow Rate)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '53.9', 'spread': '5.2', 'groupId': 'OG000'}, {'value': '40.6', 'spread': '5.2', 'groupId': 'OG001'}, {'value': '30.8', 'spread': '5.3', 'groupId': 'OG002'}, {'value': '59.0', 'spread': '5.2', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '<.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '13.1', 'ciLowerLimit': '7.2', 'ciUpperLimit': '18.9', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.0', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '23.1', 'ciLowerLimit': '17.2', 'ciUpperLimit': '28.9', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.0', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0769', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference in adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-5.3', 'ciLowerLimit': '-11.2', 'ciUpperLimit': '0.6', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.0', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and within 3 hours post-morning dose after 6 weeks of treatment.', 'description': 'Peak PEF was defined as the highest PEF reading observed within 3 hours after inhalation of the last morning dose of randomized treatment.\n\nPeak PEF response is defined as change from baseline:\n\nPeak PEF response = Peak PEF - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter/minutes (L/min)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Trough Peak Expiratory Flow Rate (PEF)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '14.4', 'spread': '4.9', 'groupId': 'OG000'}, {'value': '11.3', 'spread': '4.9', 'groupId': 'OG001'}, {'value': '7.1', 'spread': '4.9', 'groupId': 'OG002'}, {'value': '22.9', 'spread': '4.9', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.3775', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '2.8', 'ciLowerLimit': '-3.5', 'ciUpperLimit': '9.1', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.2', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0285', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '7.1', 'ciLowerLimit': '0.7', 'ciUpperLimit': '13.4', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.2', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0065', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-8.9', 'ciLowerLimit': '-15.2', 'ciUpperLimit': '-2.5', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '3.2', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.', 'description': 'Trough PEF is determined at the end of each treatment period and is defined as the pre-dose PEF measured just prior to the last administration of the morning dose of randomized treatment. Trough PEF response is defined as the change from baseline:\n\nTrough PEF response = Trough PEF - PEF (Baseline) The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.', 'unitOfMeasure': 'Liter/minutes (L/min)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set: All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Individual Forced Expiratory Volume in 1 Second (FEV1) Over a 24 Hour Observation Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'title': '0 hour', 'categories': [{'measurements': [{'value': '0.062', 'spread': '0.024', 'groupId': 'OG000'}, {'value': '0.032', 'spread': '0.024', 'groupId': 'OG001'}, {'value': '0.003', 'spread': '0.024', 'groupId': 'OG002'}, {'value': '0.097', 'spread': '0.024', 'groupId': 'OG003'}]}]}, {'title': '0.5 hour', 'categories': [{'measurements': [{'value': '0.180', 'spread': '0.024', 'groupId': 'OG000'}, {'value': '0.129', 'spread': '0.024', 'groupId': 'OG001'}, {'value': '0.068', 'spread': '0.025', 'groupId': 'OG002'}, {'value': '0.204', 'spread': '0.024', 'groupId': 'OG003'}]}]}, {'title': '1 hour', 'categories': [{'measurements': [{'value': '0.211', 'spread': '0.025', 'groupId': 'OG000'}, {'value': '0.139', 'spread': '0.025', 'groupId': 'OG001'}, {'value': '0.084', 'spread': '0.025', 'groupId': 'OG002'}, {'value': '0.236', 'spread': '0.025', 'groupId': 'OG003'}]}]}, {'title': '2 hour', 'categories': [{'measurements': [{'value': '0.242', 'spread': '0.026', 'groupId': 'OG000'}, {'value': '0.163', 'spread': '0.026', 'groupId': 'OG001'}, {'value': '0.108', 'spread': '0.026', 'groupId': 'OG002'}, {'value': '0.277', 'spread': '0.026', 'groupId': 'OG003'}]}]}, {'title': '3 hour', 'categories': [{'measurements': [{'value': '0.257', 'spread': '0.027', 'groupId': 'OG000'}, {'value': '0.167', 'spread': '0.027', 'groupId': 'OG001'}, {'value': '0.111', 'spread': '0.027', 'groupId': 'OG002'}, {'value': '0.277', 'spread': '0.027', 'groupId': 'OG003'}]}]}, {'title': '4 hour', 'categories': [{'measurements': [{'value': '0.231', 'spread': '0.027', 'groupId': 'OG000'}, {'value': '0.162', 'spread': '0.027', 'groupId': 'OG001'}, {'value': '0.102', 'spread': '0.027', 'groupId': 'OG002'}, {'value': '0.262', 'spread': '0.027', 'groupId': 'OG003'}]}]}, {'title': '6 hour', 'categories': [{'measurements': [{'value': '0.209', 'spread': '0.028', 'groupId': 'OG000'}, {'value': '0.121', 'spread': '0.028', 'groupId': 'OG001'}, {'value': '0.064', 'spread': '0.028', 'groupId': 'OG002'}, {'value': '0.218', 'spread': '0.028', 'groupId': 'OG003'}]}]}, {'title': '8 hour', 'categories': [{'measurements': [{'value': '0.167', 'spread': '0.028', 'groupId': 'OG000'}, {'value': '0.098', 'spread': '0.028', 'groupId': 'OG001'}, {'value': '0.044', 'spread': '0.028', 'groupId': 'OG002'}, {'value': '0.185', 'spread': '0.028', 'groupId': 'OG003'}]}]}, {'title': '10 hour', 'categories': [{'measurements': [{'value': '0.138', 'spread': '0.028', 'groupId': 'OG000'}, {'value': '0.080', 'spread': '0.028', 'groupId': 'OG001'}, {'value': '0.006', 'spread': '0.028', 'groupId': 'OG002'}, {'value': '0.166', 'spread': '0.028', 'groupId': 'OG003'}]}]}, {'title': '12 hour', 'categories': [{'measurements': [{'value': '0.117', 'spread': '0.027', 'groupId': 'OG000'}, {'value': '0.060', 'spread': '0.027', 'groupId': 'OG001'}, {'value': '-0.007', 'spread': '0.027', 'groupId': 'OG002'}, {'value': '0.137', 'spread': '0.027', 'groupId': 'OG003'}]}]}, {'title': '12.5 hour', 'categories': [{'measurements': [{'value': '0.101', 'spread': '0.028', 'groupId': 'OG000'}, {'value': '0.048', 'spread': '0.028', 'groupId': 'OG001'}, {'value': '0.021', 'spread': '0.028', 'groupId': 'OG002'}, {'value': '0.147', 'spread': '0.028', 'groupId': 'OG003'}]}]}, {'title': '13 hour', 'categories': [{'measurements': [{'value': '0.105', 'spread': '0.028', 'groupId': 'OG000'}, {'value': '0.043', 'spread': '0.028', 'groupId': 'OG001'}, {'value': '0.035', 'spread': '0.028', 'groupId': 'OG002'}, {'value': '0.153', 'spread': '0.028', 'groupId': 'OG003'}]}]}, {'title': '14 hour', 'categories': [{'measurements': [{'value': '0.115', 'spread': '0.029', 'groupId': 'OG000'}, {'value': '0.040', 'spread': '0.029', 'groupId': 'OG001'}, {'value': '0.031', 'spread': '0.029', 'groupId': 'OG002'}, {'value': '0.172', 'spread': '0.028', 'groupId': 'OG003'}]}]}, {'title': '22 hour', 'categories': [{'measurements': [{'value': '0.005', 'spread': '0.025', 'groupId': 'OG000'}, {'value': '-0.057', 'spread': '0.025', 'groupId': 'OG001'}, {'value': '-0.034', 'spread': '0.025', 'groupId': 'OG002'}, {'value': '0.068', 'spread': '0.025', 'groupId': 'OG003'}]}]}, {'title': '23 hour', 'categories': [{'measurements': [{'value': '0.071', 'spread': '0.025', 'groupId': 'OG000'}, {'value': '0.018', 'spread': '0.025', 'groupId': 'OG001'}, {'value': '0.008', 'spread': '0.026', 'groupId': 'OG002'}, {'value': '0.116', 'spread': '0.025', 'groupId': 'OG003'}]}]}, {'title': '24 hour', 'categories': [{'measurements': [{'value': '0.112', 'spread': '0.025', 'groupId': 'OG000'}, {'value': '0.058', 'spread': '0.025', 'groupId': 'OG001'}, {'value': '0.024', 'spread': '0.026', 'groupId': 'OG002'}, {'value': '0.147', 'spread': '0.025', 'groupId': 'OG003'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23, and 24 hours post morning dose after 6 weeks of treatment.', 'description': 'Response in individual forced expiratory volume in 1 second (FEV1) over a 24 hour observation period. Response is defined as change from baseline.\n\nMeans are adjusted for treatment, centre, treatment period and patient within centre.', 'unitOfMeasure': 'Liter (L)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Individual Forced Vital Capacity (FVC) Over a 24 Hour Observation Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'title': '0 hour', 'categories': [{'measurements': [{'value': '0.139', 'spread': '0.047', 'groupId': 'OG000'}, {'value': '0.165', 'spread': '0.047', 'groupId': 'OG001'}, {'value': '0.095', 'spread': '0.048', 'groupId': 'OG002'}, {'value': '0.229', 'spread': '0.047', 'groupId': 'OG003'}]}]}, {'title': '0.5 hour', 'categories': [{'measurements': [{'value': '0.354', 'spread': '0.049', 'groupId': 'OG000'}, {'value': '0.302', 'spread': '0.049', 'groupId': 'OG001'}, {'value': '0.200', 'spread': '0.049', 'groupId': 'OG002'}, {'value': '0.395', 'spread': '0.048', 'groupId': 'OG003'}]}]}, {'title': '1 hour', 'categories': [{'measurements': [{'value': '0.386', 'spread': '0.050', 'groupId': 'OG000'}, {'value': '0.332', 'spread': '0.050', 'groupId': 'OG001'}, {'value': '0.220', 'spread': '0.050', 'groupId': 'OG002'}, {'value': '0.411', 'spread': '0.050', 'groupId': 'OG003'}]}]}, {'title': '2 hours', 'categories': [{'measurements': [{'value': '0.409', 'spread': '0.049', 'groupId': 'OG000'}, {'value': '0.330', 'spread': '0.049', 'groupId': 'OG001'}, {'value': '0.243', 'spread': '0.050', 'groupId': 'OG002'}, {'value': '0.464', 'spread': '0.049', 'groupId': 'OG003'}]}]}, {'title': '3 hours', 'categories': [{'measurements': [{'value': '0.425', 'spread': '0.051', 'groupId': 'OG000'}, {'value': '0.319', 'spread': '0.051', 'groupId': 'OG001'}, {'value': '0.252', 'spread': '0.051', 'groupId': 'OG002'}, {'value': '0.457', 'spread': '0.051', 'groupId': 'OG003'}]}]}, {'title': '4 hours', 'categories': [{'measurements': [{'value': '0.396', 'spread': '0.050', 'groupId': 'OG000'}, {'value': '0.312', 'spread': '0.050', 'groupId': 'OG001'}, {'value': '0.223', 'spread': '0.050', 'groupId': 'OG002'}, {'value': '0.463', 'spread': '0.050', 'groupId': 'OG003'}]}]}, {'title': '6 hours', 'categories': [{'measurements': [{'value': '0.368', 'spread': '0.050', 'groupId': 'OG000'}, {'value': '0.254', 'spread': '0.051', 'groupId': 'OG001'}, {'value': '0.179', 'spread': '0.051', 'groupId': 'OG002'}, {'value': '0.399', 'spread': '0.050', 'groupId': 'OG003'}]}]}, {'title': '8 hours', 'categories': [{'measurements': [{'value': '0.309', 'spread': '0.051', 'groupId': 'OG000'}, {'value': '0.225', 'spread': '0.051', 'groupId': 'OG001'}, {'value': '0.141', 'spread': '0.051', 'groupId': 'OG002'}, {'value': '0.355', 'spread': '0.051', 'groupId': 'OG003'}]}]}, {'title': '10 hours', 'categories': [{'measurements': [{'value': '0.264', 'spread': '0.051', 'groupId': 'OG000'}, {'value': '0.185', 'spread': '0.051', 'groupId': 'OG001'}, {'value': '0.051', 'spread': '0.051', 'groupId': 'OG002'}, {'value': '0.306', 'spread': '0.051', 'groupId': 'OG003'}]}]}, {'title': '12 hours', 'categories': [{'measurements': [{'value': '0.229', 'spread': '0.050', 'groupId': 'OG000'}, {'value': '0.142', 'spread': '0.050', 'groupId': 'OG001'}, {'value': '0.051', 'spread': '0.051', 'groupId': 'OG002'}, {'value': '0.258', 'spread': '0.050', 'groupId': 'OG003'}]}]}, {'title': '12.5 hours', 'categories': [{'measurements': [{'value': '0.206', 'spread': '0.052', 'groupId': 'OG000'}, {'value': '0.131', 'spread': '0.053', 'groupId': 'OG001'}, {'value': '0.066', 'spread': '0.053', 'groupId': 'OG002'}, {'value': '0.273', 'spread': '0.052', 'groupId': 'OG003'}]}]}, {'title': '13 hours', 'categories': [{'measurements': [{'value': '0.194', 'spread': '0.052', 'groupId': 'OG000'}, {'value': '0.116', 'spread': '0.052', 'groupId': 'OG001'}, {'value': '0.106', 'spread': '0.052', 'groupId': 'OG002'}, {'value': '0.266', 'spread': '0.052', 'groupId': 'OG003'}]}]}, {'title': '14 hours', 'categories': [{'measurements': [{'value': '0.225', 'spread': '0.052', 'groupId': 'OG000'}, {'value': '0.122', 'spread': '0.052', 'groupId': 'OG001'}, {'value': '0.082', 'spread': '0.052', 'groupId': 'OG002'}, {'value': '0.287', 'spread': '0.052', 'groupId': 'OG003'}]}]}, {'title': '22 hours', 'categories': [{'measurements': [{'value': '0.081', 'spread': '0.049', 'groupId': 'OG000'}, {'value': '0.001', 'spread': '0.049', 'groupId': 'OG001'}, {'value': '-0.014', 'spread': '0.049', 'groupId': 'OG002'}, {'value': '0.191', 'spread': '0.049', 'groupId': 'OG003'}]}]}, {'title': '23 hours', 'categories': [{'measurements': [{'value': '0.176', 'spread': '0.050', 'groupId': 'OG000'}, {'value': '0.098', 'spread': '0.050', 'groupId': 'OG001'}, {'value': '0.043', 'spread': '0.050', 'groupId': 'OG002'}, {'value': '0.243', 'spread': '0.050', 'groupId': 'OG003'}]}]}, {'title': '24 hours', 'categories': [{'measurements': [{'value': '0.208', 'spread': '0.050', 'groupId': 'OG000'}, {'value': '0.153', 'spread': '0.050', 'groupId': 'OG001'}, {'value': '0.089', 'spread': '0.050', 'groupId': 'OG002'}, {'value': '0.280', 'spread': '0.050', 'groupId': 'OG003'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23 and 24 hours post morning dose after 6 weeks of treatment.', 'description': 'Response in forced vital capacity (FVC) over a 24 hour observation period. Response is defined as change from baseline.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Individual Peak Expiratory Flow (PEF) Over a 24 Hour Observation Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'title': '0 hour', 'categories': [{'measurements': [{'value': '14.4', 'spread': '4.9', 'groupId': 'OG000'}, {'value': '11.3', 'spread': '4.9', 'groupId': 'OG001'}, {'value': '7.1', 'spread': '4.9', 'groupId': 'OG002'}, {'value': '22.9', 'spread': '4.9', 'groupId': 'OG003'}]}]}, {'title': '0.5 hour', 'categories': [{'measurements': [{'value': '30.8', 'spread': '5.1', 'groupId': 'OG000'}, {'value': '20.1', 'spread': '5.2', 'groupId': 'OG001'}, {'value': '13.7', 'spread': '5.2', 'groupId': 'OG002'}, {'value': '34.3', 'spread': '5.1', 'groupId': 'OG003'}]}]}, {'title': '1 hour', 'categories': [{'measurements': [{'value': '35.5', 'spread': '5.1', 'groupId': 'OG000'}, {'value': '22.2', 'spread': '5.1', 'groupId': 'OG001'}, {'value': '14.6', 'spread': '5.1', 'groupId': 'OG002'}, {'value': '41.0', 'spread': '5.1', 'groupId': 'OG003'}]}]}, {'title': '2 hours', 'categories': [{'measurements': [{'value': '42.2', 'spread': '5.3', 'groupId': 'OG000'}, {'value': '27.6', 'spread': '5.3', 'groupId': 'OG001'}, {'value': '18.5', 'spread': '5.3', 'groupId': 'OG002'}, {'value': '47.0', 'spread': '5.2', 'groupId': 'OG003'}]}]}, {'title': '3 hours', 'categories': [{'measurements': [{'value': '45.0', 'spread': '5.4', 'groupId': 'OG000'}, {'value': '27.9', 'spread': '5.4', 'groupId': 'OG001'}, {'value': '17.1', 'spread': '5.4', 'groupId': 'OG002'}, {'value': '49.9', 'spread': '5.4', 'groupId': 'OG003'}]}]}, {'title': '4 hours', 'categories': [{'measurements': [{'value': '41.9', 'spread': '5.6', 'groupId': 'OG000'}, {'value': '26.4', 'spread': '5.6', 'groupId': 'OG001'}, {'value': '17.2', 'spread': '5.6', 'groupId': 'OG002'}, {'value': '46.5', 'spread': '5.5', 'groupId': 'OG003'}]}]}, {'title': '6 hours', 'categories': [{'measurements': [{'value': '37.8', 'spread': '5.5', 'groupId': 'OG000'}, {'value': '25.0', 'spread': '5.5', 'groupId': 'OG001'}, {'value': '11.1', 'spread': '5.5', 'groupId': 'OG002'}, {'value': '38.9', 'spread': '5.5', 'groupId': 'OG003'}]}]}, {'title': '8 hours', 'categories': [{'measurements': [{'value': '33.9', 'spread': '5.6', 'groupId': 'OG000'}, {'value': '23.3', 'spread': '5.6', 'groupId': 'OG001'}, {'value': '8.6', 'spread': '5.6', 'groupId': 'OG002'}, {'value': '35.5', 'spread': '5.6', 'groupId': 'OG003'}]}]}, {'title': '10 hours', 'categories': [{'measurements': [{'value': '26.9', 'spread': '5.7', 'groupId': 'OG000'}, {'value': '19.0', 'spread': '5.7', 'groupId': 'OG001'}, {'value': '1.9', 'spread': '5.7', 'groupId': 'OG002'}, {'value': '28.8', 'spread': '5.7', 'groupId': 'OG003'}]}]}, {'title': '12 hours', 'categories': [{'measurements': [{'value': '23.4', 'spread': '5.6', 'groupId': 'OG000'}, {'value': '11.8', 'spread': '5.6', 'groupId': 'OG001'}, {'value': '-0.6', 'spread': '5.6', 'groupId': 'OG002'}, {'value': '26.8', 'spread': '5.6', 'groupId': 'OG003'}]}]}, {'title': '12.5 hours', 'categories': [{'measurements': [{'value': '13.6', 'spread': '5.7', 'groupId': 'OG000'}, {'value': '5.5', 'spread': '5.7', 'groupId': 'OG001'}, {'value': '-0.7', 'spread': '5.8', 'groupId': 'OG002'}, {'value': '26.6', 'spread': '5.7', 'groupId': 'OG003'}]}]}, {'title': '13 hours', 'categories': [{'measurements': [{'value': '12.0', 'spread': '5.7', 'groupId': 'OG000'}, {'value': '5.8', 'spread': '5.7', 'groupId': 'OG001'}, {'value': '2.6', 'spread': '5.7', 'groupId': 'OG002'}, {'value': '25.3', 'spread': '5.6', 'groupId': 'OG003'}]}]}, {'title': '14 hours', 'categories': [{'measurements': [{'value': '15.6', 'spread': '5.7', 'groupId': 'OG000'}, {'value': '4.5', 'spread': '5.7', 'groupId': 'OG001'}, {'value': '1.4', 'spread': '5.8', 'groupId': 'OG002'}, {'value': '27.9', 'spread': '5.7', 'groupId': 'OG003'}]}]}, {'title': '22 hours', 'categories': [{'measurements': [{'value': '-4.2', 'spread': '5.1', 'groupId': 'OG000'}, {'value': '-11.7', 'spread': '5.1', 'groupId': 'OG001'}, {'value': '-9.7', 'spread': '5.1', 'groupId': 'OG002'}, {'value': '10.1', 'spread': '5.1', 'groupId': 'OG003'}]}]}, {'title': '23 hours', 'categories': [{'measurements': [{'value': '9.1', 'spread': '5.3', 'groupId': 'OG000'}, {'value': '2.3', 'spread': '5.3', 'groupId': 'OG001'}, {'value': '-5.7', 'spread': '5.3', 'groupId': 'OG002'}, {'value': '18.1', 'spread': '5.3', 'groupId': 'OG003'}]}]}, {'title': '24 hours', 'categories': [{'measurements': [{'value': '14.0', 'spread': '5.3', 'groupId': 'OG000'}, {'value': '9.6', 'spread': '5.3', 'groupId': 'OG001'}, {'value': '2.0', 'spread': '5.3', 'groupId': 'OG002'}, {'value': '24.0', 'spread': '5.3', 'groupId': 'OG003'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23, and 24 hours post morning dose after 6 weeks of treatment.', 'description': 'Response in individual peak expiratory flow (PEF) over a 24 hour observation period. Response is defined as change from baseline.\n\nMeans are adjusted for treatment, centre, treatment period and patient within centre.', 'unitOfMeasure': 'Liter/minutes (L/min)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Morning and Evening Peak Expiratory Flow Rate (PEF), Recorded by Patients at Home', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '124', 'groupId': 'OG002'}, {'value': '125', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'title': 'PEF, morning', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '124', 'groupId': 'OG002'}, {'value': '125', 'groupId': 'OG003'}]}], 'categories': [{'measurements': [{'value': '6.8', 'spread': '4.0', 'groupId': 'OG000'}, {'value': '1.2', 'spread': '4.0', 'groupId': 'OG001'}, {'value': '0.6', 'spread': '4.0', 'groupId': 'OG002'}, {'value': '14.8', 'spread': '4.0', 'groupId': 'OG003'}]}]}, {'title': 'PEF, evening', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '123', 'groupId': 'OG002'}, {'value': '123', 'groupId': 'OG003'}]}], 'categories': [{'measurements': [{'value': '16.7', 'spread': '4.9', 'groupId': 'OG000'}, {'value': '5.8', 'spread': '4.9', 'groupId': 'OG001'}, {'value': '-6.4', 'spread': '4.9', 'groupId': 'OG002'}, {'value': '15.2', 'spread': '4.9', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.0182', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '5.7', 'ciLowerLimit': '1.0', 'ciUpperLimit': '10.4', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.4', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'Morning PEF', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0091', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '6.3', 'ciLowerLimit': '1.6', 'ciUpperLimit': '11.1', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.4', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'Morning PEF', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0010', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-8.0', 'ciLowerLimit': '-12.8', 'ciUpperLimit': '-3.3', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.4', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'Morning PEF', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '11.0', 'ciLowerLimit': '5.8', 'ciUpperLimit': '16.2', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.6', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'Evening PEF', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '23.3', 'ciLowerLimit': '18.1', 'ciUpperLimit': '28.6', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.7', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'Evening PEF', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.5766', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '1.5', 'ciLowerLimit': '-3.8', 'ciUpperLimit': '6.8', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '2.7', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'Evening PEF', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'The mean PEF is defined as the mean of the values obtained during the weeks after the first three weeks of treatment. Morning and evening mean PEF were calculated and analyzed separately. PEF was measured twice daily (in the morning prior to inhalation of study medication and in the evening prior to inhalation of study medication).\n\nMorning and evening mean PEF response are defined as the change from morning and evening baseline, respectively.\n\nMorning and evening mean PEF baseline are defined as the mean of the morning and evening values, respectively obtained from the last week preceding the randomization visit.\n\nMean is adjusted for treatment, center, treatment period and patient within center.', 'unitOfMeasure': 'Liter / minute (L/min)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-Treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints'}, {'type': 'SECONDARY', 'title': 'Response in Morning and Evening Forced Expiratory Volume in 1 Second (FEV1) Recorded by Participants at Home', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '124', 'groupId': 'OG002'}, {'value': '125', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'title': 'FEV1, morning', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '124', 'groupId': 'OG002'}, {'value': '125', 'groupId': 'OG003'}]}], 'categories': [{'measurements': [{'value': '0.052', 'spread': '0.035', 'groupId': 'OG000'}, {'value': '0.013', 'spread': '0.035', 'groupId': 'OG001'}, {'value': '0.026', 'spread': '0.035', 'groupId': 'OG002'}, {'value': '0.075', 'spread': '0.035', 'groupId': 'OG003'}]}]}, {'title': 'FEV1, evening', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '123', 'groupId': 'OG002'}, {'value': '123', 'groupId': 'OG003'}]}], 'categories': [{'measurements': [{'value': '0.094', 'spread': '0.036', 'groupId': 'OG000'}, {'value': '0.038', 'spread': '0.036', 'groupId': 'OG001'}, {'value': '-0.010', 'spread': '0.036', 'groupId': 'OG002'}, {'value': '0.075', 'spread': '0.036', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.0137', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.040', 'ciLowerLimit': '0.008', 'ciUpperLimit': '0.071', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.016', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'Morning FEV1', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0981', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.027', 'ciLowerLimit': '-0.005', 'ciUpperLimit': '0.059', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.016', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'Morning FEV1', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.1827', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.022', 'ciLowerLimit': '-0.054', 'ciUpperLimit': '0.010', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.016', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'Morning FEV1', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0014', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.057', 'ciLowerLimit': '0.022', 'ciUpperLimit': '0.092', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.018', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'Evening FEV1', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '<.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.105', 'ciLowerLimit': '0.070', 'ciUpperLimit': '0.140', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.018', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'Evening FEV1', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.2584', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.020', 'ciLowerLimit': '-0.015', 'ciUpperLimit': '0.056', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.018', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'Evening FEV1', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Per treatment period, the morning mean FEV1 (mean of the pre-dose morning FEV1 measurements) and evening mean FEV1 (mean of the pre-dose evening FEV1 measurement) were calculated. Per treatment period the data obtained after the first 3 weeks were used for calculating these means.\n\nMorning and evening mean FEV1 responses are defined as the change from morning and evening baseline, respectively. The baseline values, morning and evening mean FEV1(Baseline), are defined as the mean of the morning and evening values, respectively obtained from the last week preceding the randomization visit .\n\nMean is adjusted for treatment, centre, treatment period and patient within centre.', 'unitOfMeasure': 'Liter (L)', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-Treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Mean Number of Days With Rescue Medication Use', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '124', 'groupId': 'OG002'}, {'value': '125', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18 µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'title': 'Daytime', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '124', 'groupId': 'OG002'}, {'value': '125', 'groupId': 'OG003'}]}], 'categories': [{'measurements': [{'value': '-0.08', 'spread': '0.03', 'groupId': 'OG000'}, {'value': '-0.01', 'spread': '0.03', 'groupId': 'OG001'}, {'value': '-0.06', 'spread': '0.03', 'groupId': 'OG002'}, {'value': '-0.11', 'spread': '0.03', 'groupId': 'OG003'}]}]}, {'title': 'Night-time', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '123', 'groupId': 'OG002'}, {'value': '123', 'groupId': 'OG003'}]}], 'categories': [{'measurements': [{'value': '-0.15', 'spread': '0.04', 'groupId': 'OG000'}, {'value': '-0.06', 'spread': '0.04', 'groupId': 'OG001'}, {'value': '-0.07', 'spread': '0.04', 'groupId': 'OG002'}, {'value': '-0.14', 'spread': '0.04', 'groupId': 'OG003'}]}]}, {'title': '24 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'OG000'}, {'value': '125', 'groupId': 'OG001'}, {'value': '121', 'groupId': 'OG002'}, {'value': '123', 'groupId': 'OG003'}]}], 'categories': [{'measurements': [{'value': '-0.13', 'spread': '0.04', 'groupId': 'OG000'}, {'value': '-0.04', 'spread': '0.04', 'groupId': 'OG001'}, {'value': '-0.06', 'spread': '0.04', 'groupId': 'OG002'}, {'value': '-0.14', 'spread': '0.04', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.0027', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.07', 'ciLowerLimit': '-0.11', 'ciUpperLimit': '-0.02', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.02', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'Daytime', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.4587', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.02', 'ciLowerLimit': '-0.06', 'ciUpperLimit': '0.03', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.02', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'Daytime', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.1535', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.03', 'ciLowerLimit': '-0.01', 'ciUpperLimit': '0.08', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.02', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'Daytime', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0002', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.09', 'ciLowerLimit': '-0.14', 'ciUpperLimit': '-0.05', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.02', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'Night-time', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0006', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.09', 'ciLowerLimit': '-0.14', 'ciUpperLimit': '-0.04', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.03', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'Night-time', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.5784', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.01', 'ciLowerLimit': '-0.06', 'ciUpperLimit': '0.04', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.03', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'Night-time', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0003', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.09', 'ciLowerLimit': '-0.14', 'ciUpperLimit': '-0.04', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.02', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': '24 hours', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0042', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.07', 'ciLowerLimit': '-0.12', 'ciUpperLimit': '-0.02', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.02', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': '24 hours', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.9978', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.00', 'ciLowerLimit': '-0.05', 'ciUpperLimit': '0.05', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.03', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': '24 hours', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Response (change from baseline) in mean number of days with rescue medication use in day-time, night-time and 24-hours. Per treatment period, the response in mean number of days using rescue medication was calculated for day-time (from inhalation of morning dose until 12 hours thereafter), night-time (from inhalation of evening dose until 12 hours thereafter) and 24h-total (from inhalation of morning dose until 24 hours thereafter) separately.\n\nPer 6-week treatment period the data obtained after the first 3 weeks was used for calculating means. Mean is adjusted mean.', 'unitOfMeasure': 'Days', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Mean Number of Puffs of Rescue Medication', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18 µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'title': 'Daytime', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '123', 'groupId': 'OG002'}, {'value': '123', 'groupId': 'OG003'}]}], 'categories': [{'measurements': [{'value': '-0.61', 'spread': '0.18', 'groupId': 'OG000'}, {'value': '-0.27', 'spread': '0.18', 'groupId': 'OG001'}, {'value': '-0.25', 'spread': '0.18', 'groupId': 'OG002'}, {'value': '-0.65', 'spread': '0.18', 'groupId': 'OG003'}]}]}, {'title': 'Night-time', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '124', 'groupId': 'OG002'}, {'value': '125', 'groupId': 'OG003'}]}], 'categories': [{'measurements': [{'value': '-0.16', 'spread': '0.12', 'groupId': 'OG000'}, {'value': '0.01', 'spread': '0.12', 'groupId': 'OG001'}, {'value': '-0.07', 'spread': '0.12', 'groupId': 'OG002'}, {'value': '-0.28', 'spread': '0.12', 'groupId': 'OG003'}]}]}, {'title': 'Over 24 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '126', 'groupId': 'OG000'}, {'value': '125', 'groupId': 'OG001'}, {'value': '121', 'groupId': 'OG002'}, {'value': '123', 'groupId': 'OG003'}]}], 'categories': [{'measurements': [{'value': '-0.76', 'spread': '0.28', 'groupId': 'OG000'}, {'value': '-0.23', 'spread': '0.28', 'groupId': 'OG001'}, {'value': '-0.30', 'spread': '0.28', 'groupId': 'OG002'}, {'value': '-0.92', 'spread': '0.28', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.0029', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.33', 'ciLowerLimit': '-0.55', 'ciUpperLimit': '-0.11', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.11', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'Daytime', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0012', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.36', 'ciLowerLimit': '-0.58', 'ciUpperLimit': '-0.14', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.11', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'Daytime', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0829', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.12', 'ciLowerLimit': '-0.02', 'ciUpperLimit': '0.25', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.07', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'Daytime', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0115', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.17', 'ciLowerLimit': '-0.30', 'ciUpperLimit': '-0.04', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.07', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'Night-time', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.1772', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.09', 'ciLowerLimit': '-0.22', 'ciUpperLimit': '0.04', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.07', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'Night-time', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.6895', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.04', 'ciLowerLimit': '-0.18', 'ciUpperLimit': '0.27', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.11', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'Night-time', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0013', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.52', 'ciLowerLimit': '-0.84', 'ciUpperLimit': '-0.21', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.16', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'groupDescription': 'Over 24 hours', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0040', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.47', 'ciLowerLimit': '-0.78', 'ciUpperLimit': '-0.15', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.16', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'groupDescription': 'Over 24 hours', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.3287', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.16', 'ciLowerLimit': '-0.16', 'ciUpperLimit': '0.48', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.16', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'groupDescription': 'Over 24 hours', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Response in mean number of puffs of rescue medication. Per treatment period, the response in mean number of puffs rescue medication used was calculated, for day-time (from inhalation of morning dose until 12 hours thereafter), night-time (from inhalation of evening dose until 12 hours thereafter) and 24h-total (from inhalation of morning dose until 24 hours thereafter) separately. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating means. Night-time, day-time and 24h-total mean number of puffs rescue medication used responses are defined as the change from night-time, day-time and 24h-total baseline, respectively.\n\nThe baseline values, night-time, day-time and 24h-total mean mean number of puffs rescue medication used (Baseline), are defined as the mean of the night-time, day-time and 24h-total values, respectively obtained from the last week preceding the randomisation visit.', 'unitOfMeasure': 'Puffs', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Mean Number of Days With Night-time Awakenings', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '124', 'groupId': 'OG002'}, {'value': '125', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18 µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.06', 'spread': '0.03', 'groupId': 'OG000'}, {'value': '-0.06', 'spread': '0.03', 'groupId': 'OG001'}, {'value': '-0.05', 'spread': '0.03', 'groupId': 'OG002'}, {'value': '0.07', 'spread': '0.03', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.9956', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.00', 'ciLowerLimit': '-0.03', 'ciUpperLimit': '0.03', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.01', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.7100', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.01', 'ciLowerLimit': '-0.03', 'ciUpperLimit': '0.02', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.01', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.3659', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.01', 'ciLowerLimit': '-0.02', 'ciUpperLimit': '0.04', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.01', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Response in mean number of days with night-time awakenings. Per treatment period, the mean number days with awakening during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating this mean. Mean number of days with night-time awakenings response is defined as the change from baseline. The baseline value, mean number of days with night-time awakenings (Baseline), is defined as the mean of the number of days with night-time awakenings obtained from the last week preceding the randomization visit.', 'unitOfMeasure': 'Days', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Mean Number of Days With Night-time Awakenings Due to Shortness of Breath (SOB)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '124', 'groupId': 'OG002'}, {'value': '125', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18 µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.05', 'spread': '0.02', 'groupId': 'OG000'}, {'value': '-0.04', 'spread': '0.02', 'groupId': 'OG001'}, {'value': '-0.04', 'spread': '0.02', 'groupId': 'OG002'}, {'value': '-0.07', 'spread': '0.02', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.4416', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.01', 'ciLowerLimit': '-0.04', 'ciUpperLimit': '0.02', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.01', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.7058', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.01', 'ciLowerLimit': '-0.03', 'ciUpperLimit': '0.02', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.01', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.1494', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.02', 'ciLowerLimit': '-0.01', 'ciUpperLimit': '0.05', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.01', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Per treatment period, the mean number days with awakening (only chronic obstructive pulmonary disease (COPD) related awakenings) during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating the mean.\n\nMean number of days with COPD related awakenings response is defined as the change from baseline.\n\nThe baseline value, mean number of days with COPD related awakenings (Baseline), is defined as the mean of the number of days with COPD related awakenings obtained from the last week preceding the randomization visit.', 'unitOfMeasure': 'Days', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Means Number of Awakenings Due to Shortness of Breath (SOB)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '124', 'groupId': 'OG002'}, {'value': '125', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18 µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.02', 'spread': '0.04', 'groupId': 'OG000'}, {'value': '-0.02', 'spread': '0.04', 'groupId': 'OG001'}, {'value': '-0.04', 'spread': '0.04', 'groupId': 'OG002'}, {'value': '-0.08', 'spread': '0.04', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.9980', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.00', 'ciLowerLimit': '-0.06', 'ciUpperLimit': '0.06', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.03', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.4618', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.02', 'ciLowerLimit': '-0.04', 'ciUpperLimit': '0.08', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.03', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.0418', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.06', 'ciLowerLimit': '0.00', 'ciUpperLimit': '0.12', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.03', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Per treatment period, the mean number of awakening (only chronic obstructive pulmonary disease (COPD) related awakenings) during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating this mean. Mean number of COPD related awakenings response is defined as the change from baseline. The baseline value, mean number of COPD related awakenings (Baseline), is defined as the mean of the number of days with COPD related awakenings obtained from the last week preceding the randomization visit.', 'unitOfMeasure': 'Awakenings', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Response in Average Shortness of Breath (SOB) Score at Night', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '127', 'groupId': 'OG001'}, {'value': '124', 'groupId': 'OG002'}, {'value': '125', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18 µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.06', 'spread': '0.05', 'groupId': 'OG000'}, {'value': '-0.04', 'spread': '0.05', 'groupId': 'OG001'}, {'value': '-0.06', 'spread': '0.05', 'groupId': 'OG002'}, {'value': '-0.11', 'spread': '0.05', 'groupId': 'OG003'}]}]}], 'analyses': [{'pValue': '0.4206', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.02', 'ciLowerLimit': '-0.08', 'ciUpperLimit': '0.03', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.03', 'estimateComment': '(T+S\\_PE) - (Tio18GEL)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.8723', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.00', 'ciLowerLimit': '-0.05', 'ciUpperLimit': '0.06', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.03', 'estimateComment': '(T+S\\_PE) - (Salm50DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}, {'pValue': '0.1005', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Difference of adjusted means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.05', 'ciLowerLimit': '-0.01', 'ciUpperLimit': '0.11', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.03', 'estimateComment': '(T+S\\_PE) - (T18GEL+S-DPI)', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Analysis of variance with terms for centre, patient within centre, treatment, and period. α = 0.05 two-sided.'}], 'paramType': 'MEAN', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Response in average shortness of breath (SOB) score at night. The SOB measured the shortness of breath, ranging from 1 to 5, where 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit and 5 = very much. A higher score indicates a worse outcome.\n\nPer 6-week treatment period the data obtained after the first 3 weeks was used for calculating the mean.', 'unitOfMeasure': 'Score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Drug Related Adverse Events', 'denoms': [{'units': 'Participants', 'counts': [{'value': '132', 'groupId': 'OG000'}, {'value': '135', 'groupId': 'OG001'}, {'value': '137', 'groupId': 'OG002'}, {'value': '132', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18 µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}, {'value': '2', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'From first drug administration until last drug administration (average duration of 42 days) + 30 days, up to 91 days for T+S_PE, up to 98 days for Tio18GEL, up 89 days for Salm50DPI and up to 113 days for T18GEL+S_DPI.', 'description': 'Number of participants with drug related adverse events.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Treated Set (TS): All randomised patients who took at least one dose of study medication.'}, {'type': 'SECONDARY', 'title': 'Number of Patients With Marked Changes in Vital Signs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '127', 'groupId': 'OG000'}, {'value': '128', 'groupId': 'OG001'}, {'value': '125', 'groupId': 'OG002'}, {'value': '127', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': '7.5 µg /25 µg Tio /Salmeterol (T+S_PE)', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG001', 'title': '18 µg Tiotropium (Tio18GEL)', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG002', 'title': '50 µg Salmeterol MDPI (Salm50DPI)', 'description': 'One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID) in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'OG003', 'title': '18 µg Tiotropium Free Combination (T18GEL+S_DPI)', 'description': '18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'classes': [{'title': 'Increase in systolic blood pressure', 'categories': [{'measurements': [{'value': '18', 'groupId': 'OG000'}, {'value': '18', 'groupId': 'OG001'}, {'value': '16', 'groupId': 'OG002'}, {'value': '15', 'groupId': 'OG003'}]}]}, {'title': 'Increase in diastolic blood pressure', 'categories': [{'measurements': [{'value': '16', 'groupId': 'OG000'}, {'value': '16', 'groupId': 'OG001'}, {'value': '11', 'groupId': 'OG002'}, {'value': '14', 'groupId': 'OG003'}]}]}, {'title': 'Increase in pulse rate', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}, {'value': '9', 'groupId': 'OG002'}, {'value': '13', 'groupId': 'OG003'}]}]}, {'title': 'Decrease in systolic blood pressure', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}, {'value': '3', 'groupId': 'OG002'}, {'value': '4', 'groupId': 'OG003'}]}]}, {'title': 'Decrease in diastolic blood pressure', 'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}, {'value': '3', 'groupId': 'OG002'}, {'value': '5', 'groupId': 'OG003'}]}]}, {'title': 'Decrease in pulse rate', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}, {'value': '7', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'At baseline and 6 hours following the morning dose of study medication after 6 weeks of treatment.', 'description': 'Marked changes from baseline in vital signs were defined as followed:\n\nSystolic blood pressure\n\n* Increase of ≥25 millimetre of mercury (mmHg) above baseline\n* Decrease below 100 mmHg if not at that level at baseline and a decrease of \\>10 mmHg below baseline\n\nDiastolic blood pressure\n\n* Increase above 90 mmHg and an increase of \\>10 mmHg above baseline\n* Decrease below 60 mmHg if not at that level at baseline and a decrease of \\>10 mmHg below baseline\n\nPulse\n\n* Increase above 100 bpm if not at that level at baseline and an increase of \\>10 bpm above baseline\n* Decrease below 60 bpm if not at that level at baseline and a decrease of \\>10 bpm below baseline\n\nBaseline is defined as the pre-dose measurement at randomisation visit.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Treated Set (TS): All randomised patients who took at least one dose of study medication and who had available data.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI', 'description': 'Period 1: Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening.\n\nPeriod 2: 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening.\n\nPeriod 3: One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID), in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning.\n\nPeriod 4: 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning.\n\nEach dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'FG001', 'title': 'Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI', 'description': 'Period 1: 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening.\n\nPeriod 2:\n\n18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning.\n\nPeriod 3: Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening.\n\nPeriod 4: One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID), in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'FG002', 'title': 'Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL', 'description': 'Period 1: One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID), in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning.\n\nPeriod 2: Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening.\n\nPeriod 3: 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning.\n\nPeriod 4: 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}, {'id': 'FG003', 'title': 'T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE', 'description': 'Period 1: 18 µg Tiotropium (T18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® in the morning plus one actuation of 50 µg Salmeterol MDPI (S\\_DPI) BID, in the morning and in the evening, and one placebo capsule from blue Handi Haler® in the morning. Period 2: One actuation of 50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID), in the morning and in the evening, one capsule of matching placebo from grey HandiHaler® and one capsule of matching placebo from the blue HandiHaler® in the morning. Period 3: 18 µg Tiotropium (Tio18GEL) inhalation powder from one capsule via the grey Spiriva HandyHaler® QD in the morning, one capsule of matching placebo via the blue HandiHaler® and one actuation from the placebo MDPI in the morning and one actuation from the placebo MDPI in the evening. Period 4: Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder from one capsule via the blue HandiHaler® once daily (QD) in the morning, one capsule of matching placebo via the grey HandiHaler® and one actuation from the placebo Multi-Dose Powder Inhaler (MDPI) in the morning and one actuation from the placebo MDPI in the evening. Each dose of study medication had to be taken approximately at the same time, with 12 hours between the evening and morning dose. Each treatment period was 6 weeks on average with no wash-out between the treatment periods.'}], 'periods': [{'title': 'Period 1', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '34'}, {'groupId': 'FG001', 'numSubjects': '38'}, {'groupId': 'FG002', 'numSubjects': '36'}, {'groupId': 'FG003', 'numSubjects': '39'}]}, {'type': 'Treated', 'achievements': [{'groupId': 'FG000', 'numSubjects': '34'}, {'groupId': 'FG001', 'numSubjects': '37'}, {'groupId': 'FG002', 'numSubjects': '36'}, {'groupId': 'FG003', 'numSubjects': '39'}]}, {'type': 'COMPLETED', 'comment': 'Not prematurely discontinued study medication', 'achievements': [{'groupId': 'FG000', 'numSubjects': '32'}, {'groupId': 'FG001', 'numSubjects': '31'}, {'groupId': 'FG002', 'numSubjects': '32'}, {'groupId': 'FG003', 'numSubjects': '39'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '7'}, {'groupId': 'FG002', 'numSubjects': '4'}, {'groupId': 'FG003', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Personal Reasons', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '0'}]}, {'type': 'Refused continuing medication', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '0'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}]}, {'type': 'Other adverse event (AE)', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}]}, {'type': 'Worsening of disease under study (AE)', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '3'}, {'groupId': 'FG002', 'numSubjects': '2'}, {'groupId': 'FG003', 'numSubjects': '0'}]}, {'type': 'Not treated', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}]}]}, {'title': 'Period 2', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '32'}, {'groupId': 'FG001', 'numSubjects': '31'}, {'groupId': 'FG002', 'numSubjects': '32'}, {'groupId': 'FG003', 'numSubjects': '39'}]}, {'type': 'Treated', 'achievements': [{'groupId': 'FG000', 'numSubjects': '32'}, {'groupId': 'FG001', 'numSubjects': '31'}, {'groupId': 'FG002', 'numSubjects': '32'}, {'groupId': 'FG003', 'numSubjects': '39'}]}, {'type': 'COMPLETED', 'comment': 'Not prematurely discontinued from study medication', 'achievements': [{'groupId': 'FG000', 'numSubjects': '31'}, {'groupId': 'FG001', 'numSubjects': '31'}, {'groupId': 'FG002', 'numSubjects': '32'}, {'groupId': 'FG003', 'numSubjects': '36'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Worsening of disease under study', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '3'}]}]}, {'title': 'Period 3', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '31'}, {'groupId': 'FG001', 'numSubjects': '31'}, {'groupId': 'FG002', 'numSubjects': '32'}, {'groupId': 'FG003', 'numSubjects': '36'}]}, {'type': 'Treated', 'achievements': [{'groupId': 'FG000', 'numSubjects': '31'}, {'groupId': 'FG001', 'numSubjects': '31'}, {'groupId': 'FG002', 'numSubjects': '32'}, {'groupId': 'FG003', 'numSubjects': '36'}]}, {'type': 'COMPLETED', 'comment': 'Not prematurely discontinued from study medication', 'achievements': [{'groupId': 'FG000', 'numSubjects': '30'}, {'groupId': 'FG001', 'numSubjects': '31'}, {'groupId': 'FG002', 'numSubjects': '30'}, {'groupId': 'FG003', 'numSubjects': '35'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '2'}, {'groupId': 'FG003', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Refused continuing medication', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '0'}]}, {'type': 'Other adverse event (AE)', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}, {'groupId': 'FG003', 'numSubjects': '1'}]}]}, {'title': 'Period 4', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '30'}, {'groupId': 'FG001', 'numSubjects': '31'}, {'groupId': 'FG002', 'numSubjects': '30'}, {'groupId': 'FG003', 'numSubjects': '35'}]}, {'type': 'Treated', 'achievements': [{'groupId': 'FG000', 'numSubjects': '30'}, {'groupId': 'FG001', 'numSubjects': '31'}, {'groupId': 'FG002', 'numSubjects': '30'}, {'groupId': 'FG003', 'numSubjects': '35'}]}, {'type': 'COMPLETED', 'comment': 'Not prematurely discontinued from study medication', 'achievements': [{'groupId': 'FG000', 'numSubjects': '29'}, {'groupId': 'FG001', 'numSubjects': '30'}, {'groupId': 'FG002', 'numSubjects': '30'}, {'groupId': 'FG003', 'numSubjects': '34'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Refused continuing medication', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}]}, {'type': 'Other adverse event (AE)', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}]}, {'type': 'Worsening of disease under study (AE)', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'Randomised, double-blind, 4-way crossover efficacy and safety comparison of Tiotropium/Salmeterol, Tiotropium Salmeterol and the free combination Tiotropium plus Salmeterol (50 μg) following chronic Administration in patients with COPD.\n\nPatients received each of the 4 treatments for 6 weeks in a randomised sequence.', 'preAssignmentDetails': 'All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '146', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Study Total', 'description': 'Total number of patients treated in the study. This was a randomized, double-blind 4-way cross over study. Patients were assigned randomly to one of 4 treatment sequences in which they received each of the 4 treatments (7.5 µg/25 µg Tio/Salmeterol, 18 µg Tiotropium, 50 µg Salmeterol MDPI and 18 µg Tiotropium Free combination). The duration of each treatment period was 6 weeks on average with no washout period between treatments.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '146', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '61.4', 'spread': '7.6', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '146', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '53', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '93', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '146', 'groupId': 'BG000'}]}], 'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '143', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'FEV1 AUC0-12 at baseline', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '135', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '1.55', 'spread': '0.51', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'description': 'FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 12 h (FEV1 AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FEV1 AUC0-12 at baseline is reported.', 'unitOfMeasure': 'Liter (L)', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available.'}], 'populationDescription': 'Treated Set: All randomised patients who took at least one dose of study medication.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 147}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2008-04-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-06', 'dispFirstSubmitDate': '2014-04-30', 'completionDateStruct': {'date': '2009-07-22', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-06-27', 'studyFirstSubmitDate': '2008-04-17', 'dispFirstSubmitQcDate': '2014-04-30', 'resultsFirstSubmitDate': '2022-04-07', 'studyFirstSubmitQcDate': '2008-04-18', 'dispFirstPostDateStruct': {'date': '2014-05-16', 'type': 'ESTIMATED'}, 'lastUpdatePostDateStruct': {'date': '2022-06-28', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2022-06-27', 'studyFirstPostDateStruct': {'date': '2008-04-21', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2022-06-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2009-07-22', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 - 12 Hours (AUC0-12)', 'timeFrame': 'At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment.', 'description': 'FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 12 h (FEV1 AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FEV1 AUC0-12h response is defined as the change from baseline:\n\nFEV1 AUC0-12h response = FEV1 AUC0-12h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Forced Expiratory Volume in Second (FEV1) Area Under the Curve From 12 - 24 Hours (AUC12 -24)', 'timeFrame': 'At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'The FEV1 AUC was defined as the area under the FEV1 curve (AUC) normalised for time. It was calculated from time 12 to 24 h (FEV1 AUC12-24), using the trapezoidal rule divided by the corresponding duration (i.e. 12 h) to give the results in L.\n\nAUC12-24h response is defined as the change from baseline:\n\nFEV1 AUC12-24h response = FEV1 AUC12-24h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit (Visit 2) just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Peak Forced Expiratory Volume in 1 Second (FEV1)', 'timeFrame': 'At baseline and within 3 hours post-morning dose after 6 weeks of treatment.', 'description': 'Peak FEV1 was defined as the highest FEV1 reading observed within 3 hours after inhalation of the last morning dose of each randomized treatment. Peak FEV1 response is defined as change from baseline:\n\nPeak FEV1 response = Peak FEV1 - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Trough Forced Expiratory Volume in 1 Second (FEV1)', 'timeFrame': 'At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.', 'description': 'Trough FEV1 is determined at the end of each treatment period and is defined as the pre-dose FEV1 measured just prior to the last administration of the morning dose of randomized treatment.\n\nTrough FEV1 response is defined as the change from baseline:\n\nTrough FEV1 response = Trough FEV1 - FEV1 (Baseline) The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}], 'secondaryOutcomes': [{'measure': 'Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0-24 Hours (AUC0-24)', 'timeFrame': 'At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 24 h (FEV1 AUC0-24), using the trapezoidal rule divided by the corresponding duration (24 h) to give the results in liter (L). FEV1 AUC0-24h response is defined as the change from baseline:\n\nFEV1 AUC0-24h response = FEV1 AUC0-24h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 to 12 Hours (AUC0-12)', 'timeFrame': 'At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment.', 'description': 'FVC AUC was defined as the area under the FVC curve normalized for time. It was calculated from time 0 to 12 h (FVC AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FVC AUC0-12h response is defined as the change from baseline:\n\nFVC AUC0-12h response = FVC AUC0-12h - FVC (Baseline). The baseline value for FVC based parameters is defined as the pre-dose FVC measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Forced Vital Capacity (FVC) Area Under the Curve From 12 to 24 Hours (AUC12-24)', 'timeFrame': 'At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 10, 11 and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'The FVC AUC was defined as the area under the FVC curve (AUC) normalised for time. It was calculated from time 12 to 24 h (FVC AUC12-24), using the trapezoidal rule divided by the corresponding duration (i.e. 12 h) to give the results in L.\n\nAUC12-24h response is defined as the change from baseline:\n\nFVC AUC12-24h response = FVC AUC12-24h - FVC (Baseline). The FVC baseline value is defined as the pre-dose FVC measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 - 24 Hours (AUC0-24)', 'timeFrame': 'At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hour after inhalation the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'The FVC AUC was defined as the area under the FVC curve (AUC) normalised for time. It was calculated from time 0 to 24 h (FVC AUC0-24), using the trapezoidal rule divided by the corresponding duration (i.e. 24 h) to give the results in L. AUC response was defined as the change from the baseline FVC; baseline was defined as the FVC measured on randomisation visit. Mean is adjusted mean.'}, {'measure': 'Response in Peak Forced Vital Capacity (FVC)', 'timeFrame': 'At baseline and within 3 hours post-morning dose after 6 weeks of treatment.', 'description': 'Peak FEV1 was defined as the highest FEV1 reading observed within 3 hours after inhalation of the last morning dose of each randomized treatment.\n\nPeak FEV1 response is defined as change from baseline:\n\nPeak FEV1 response = Peak FEV1 - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Trough Forced Vital Capacity (FVC)', 'timeFrame': 'At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.', 'description': 'Trough FVC1 is determined at the end of each 6-week treatment period and is defined as the pre-dose FVC1 measured just prior to the last administration of the morning dose of randomized treatment.\n\nTrough FVC1 response is defined as the change from baseline:\n\nTrough FVC1 response = Trough FVC1 - FVC1 (Baseline) The FVC1 baseline value is defined as the pre-dose FVC1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve Form 0 to 12 Hours (AUC0-12)', 'timeFrame': 'At baseline and 10 minutes (min) prior and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment.', 'description': 'PEF(L/min) AUC0-12(h) response is defined as the change from baseline. AUC0-12(h) was calculated as the area under the curve from 0 to 12 hours using the trapezoidal rule, divided by the full duration (12 hours) to report in liter/minutes.\n\nPEF AUC0-12h response = PEF AUC0-12h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 12 to 24 Hours (AUC12-24)', 'timeFrame': 'At baseline and 10 minutes (min) prior and 30 min, 60 min, 2, 10, 11 and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'PEF(L/min) AUC12-24(h) response is defined as the change from baseline. AUC12-24(h) was calculated as the area under the curve from 12 to 24 hours using the trapezoidal rule, divided by the full duration (12 hours) to report in liter/minutes.\n\nPEF AUC12-24h response = PEF AUC12-24h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 0 to 24 Hours (AUC0-24)', 'timeFrame': 'At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.', 'description': 'PEF(L/min) AUC0-24(h) response is defined as the change from baseline. AUC0-24(h) was calculated as the area under the curve from 0 to 24 hours using the trapezoidal rule, divided by the full duration (24 hours) to report in liter/minutes.\n\nPEF AUC0-24h response = PEF AUC0-24h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Peak PEF (Peak Expiratory Flow Rate)', 'timeFrame': 'At baseline and within 3 hours post-morning dose after 6 weeks of treatment.', 'description': 'Peak PEF was defined as the highest PEF reading observed within 3 hours after inhalation of the last morning dose of randomized treatment.\n\nPeak PEF response is defined as change from baseline:\n\nPeak PEF response = Peak PEF - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Trough Peak Expiratory Flow Rate (PEF)', 'timeFrame': 'At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.', 'description': 'Trough PEF is determined at the end of each treatment period and is defined as the pre-dose PEF measured just prior to the last administration of the morning dose of randomized treatment. Trough PEF response is defined as the change from baseline:\n\nTrough PEF response = Trough PEF - PEF (Baseline) The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.'}, {'measure': 'Response in Individual Forced Expiratory Volume in 1 Second (FEV1) Over a 24 Hour Observation Period', 'timeFrame': 'At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23, and 24 hours post morning dose after 6 weeks of treatment.', 'description': 'Response in individual forced expiratory volume in 1 second (FEV1) over a 24 hour observation period. Response is defined as change from baseline.\n\nMeans are adjusted for treatment, centre, treatment period and patient within centre.'}, {'measure': 'Response in Individual Forced Vital Capacity (FVC) Over a 24 Hour Observation Period', 'timeFrame': 'At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23 and 24 hours post morning dose after 6 weeks of treatment.', 'description': 'Response in forced vital capacity (FVC) over a 24 hour observation period. Response is defined as change from baseline.'}, {'measure': 'Response in Individual Peak Expiratory Flow (PEF) Over a 24 Hour Observation Period', 'timeFrame': 'At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23, and 24 hours post morning dose after 6 weeks of treatment.', 'description': 'Response in individual peak expiratory flow (PEF) over a 24 hour observation period. Response is defined as change from baseline.\n\nMeans are adjusted for treatment, centre, treatment period and patient within centre.'}, {'measure': 'Response in Morning and Evening Peak Expiratory Flow Rate (PEF), Recorded by Patients at Home', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'The mean PEF is defined as the mean of the values obtained during the weeks after the first three weeks of treatment. Morning and evening mean PEF were calculated and analyzed separately. PEF was measured twice daily (in the morning prior to inhalation of study medication and in the evening prior to inhalation of study medication).\n\nMorning and evening mean PEF response are defined as the change from morning and evening baseline, respectively.\n\nMorning and evening mean PEF baseline are defined as the mean of the morning and evening values, respectively obtained from the last week preceding the randomization visit.\n\nMean is adjusted for treatment, center, treatment period and patient within center.'}, {'measure': 'Response in Morning and Evening Forced Expiratory Volume in 1 Second (FEV1) Recorded by Participants at Home', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Per treatment period, the morning mean FEV1 (mean of the pre-dose morning FEV1 measurements) and evening mean FEV1 (mean of the pre-dose evening FEV1 measurement) were calculated. Per treatment period the data obtained after the first 3 weeks were used for calculating these means.\n\nMorning and evening mean FEV1 responses are defined as the change from morning and evening baseline, respectively. The baseline values, morning and evening mean FEV1(Baseline), are defined as the mean of the morning and evening values, respectively obtained from the last week preceding the randomization visit .\n\nMean is adjusted for treatment, centre, treatment period and patient within centre.'}, {'measure': 'Response in Mean Number of Days With Rescue Medication Use', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Response (change from baseline) in mean number of days with rescue medication use in day-time, night-time and 24-hours. Per treatment period, the response in mean number of days using rescue medication was calculated for day-time (from inhalation of morning dose until 12 hours thereafter), night-time (from inhalation of evening dose until 12 hours thereafter) and 24h-total (from inhalation of morning dose until 24 hours thereafter) separately.\n\nPer 6-week treatment period the data obtained after the first 3 weeks was used for calculating means. Mean is adjusted mean.'}, {'measure': 'Response in Mean Number of Puffs of Rescue Medication', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Response in mean number of puffs of rescue medication. Per treatment period, the response in mean number of puffs rescue medication used was calculated, for day-time (from inhalation of morning dose until 12 hours thereafter), night-time (from inhalation of evening dose until 12 hours thereafter) and 24h-total (from inhalation of morning dose until 24 hours thereafter) separately. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating means. Night-time, day-time and 24h-total mean number of puffs rescue medication used responses are defined as the change from night-time, day-time and 24h-total baseline, respectively.\n\nThe baseline values, night-time, day-time and 24h-total mean mean number of puffs rescue medication used (Baseline), are defined as the mean of the night-time, day-time and 24h-total values, respectively obtained from the last week preceding the randomisation visit.'}, {'measure': 'Response in Mean Number of Days With Night-time Awakenings', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Response in mean number of days with night-time awakenings. Per treatment period, the mean number days with awakening during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating this mean. Mean number of days with night-time awakenings response is defined as the change from baseline. The baseline value, mean number of days with night-time awakenings (Baseline), is defined as the mean of the number of days with night-time awakenings obtained from the last week preceding the randomization visit.'}, {'measure': 'Response in Mean Number of Days With Night-time Awakenings Due to Shortness of Breath (SOB)', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Per treatment period, the mean number days with awakening (only chronic obstructive pulmonary disease (COPD) related awakenings) during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating the mean.\n\nMean number of days with COPD related awakenings response is defined as the change from baseline.\n\nThe baseline value, mean number of days with COPD related awakenings (Baseline), is defined as the mean of the number of days with COPD related awakenings obtained from the last week preceding the randomization visit.'}, {'measure': 'Response in Means Number of Awakenings Due to Shortness of Breath (SOB)', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Per treatment period, the mean number of awakening (only chronic obstructive pulmonary disease (COPD) related awakenings) during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating this mean. Mean number of COPD related awakenings response is defined as the change from baseline. The baseline value, mean number of COPD related awakenings (Baseline), is defined as the mean of the number of days with COPD related awakenings obtained from the last week preceding the randomization visit.'}, {'measure': 'Response in Average Shortness of Breath (SOB) Score at Night', 'timeFrame': 'At baseline and last 3 weeks of 6-week treatment period.', 'description': 'Response in average shortness of breath (SOB) score at night. The SOB measured the shortness of breath, ranging from 1 to 5, where 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit and 5 = very much. A higher score indicates a worse outcome.\n\nPer 6-week treatment period the data obtained after the first 3 weeks was used for calculating the mean.'}, {'measure': 'Number of Participants With Drug Related Adverse Events', 'timeFrame': 'From first drug administration until last drug administration (average duration of 42 days) + 30 days, up to 91 days for T+S_PE, up to 98 days for Tio18GEL, up 89 days for Salm50DPI and up to 113 days for T18GEL+S_DPI.', 'description': 'Number of participants with drug related adverse events.'}, {'measure': 'Number of Patients With Marked Changes in Vital Signs', 'timeFrame': 'At baseline and 6 hours following the morning dose of study medication after 6 weeks of treatment.', 'description': 'Marked changes from baseline in vital signs were defined as followed:\n\nSystolic blood pressure\n\n* Increase of ≥25 millimetre of mercury (mmHg) above baseline\n* Decrease below 100 mmHg if not at that level at baseline and a decrease of \\>10 mmHg below baseline\n\nDiastolic blood pressure\n\n* Increase above 90 mmHg and an increase of \\>10 mmHg above baseline\n* Decrease below 60 mmHg if not at that level at baseline and a decrease of \\>10 mmHg below baseline\n\nPulse\n\n* Increase above 100 bpm if not at that level at baseline and an increase of \\>10 bpm above baseline\n* Decrease below 60 bpm if not at that level at baseline and a decrease of \\>10 bpm below baseline\n\nBaseline is defined as the pre-dose measurement at randomisation visit.'}]}, 'conditionsModule': {'conditions': ['Pulmonary Disease, Chronic Obstructive']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'http://www.mystudywindow.com/', 'label': 'Related Info'}]}, 'descriptionModule': {'briefSummary': 'The primary objective of this trial is to establish superiority of the once-daily Tiotropium plus Salmeterol Inhalation Powder in daytime lung function response and non-inferiority in night-time lung function response over the comparator treatments inhaled in their established dose regimens when administered for 6-week periods to patients with chronic obstructive pulmonary disease (COPD). The main secondary objective is to evaluate the safety of the Tiotropium plus Salmeterol Inhalation Powder versus the comparator treatments.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '40 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. All patients must sign an informed consent consistent with ICH-GCP guidelines and local legislations prior to any study-related procedures, which includes medication washout and restrictions.\n2. All patients must have a diagnosis of COPD and must meet the following criteria:\n\n relatively stable\\* airway obstruction with a post-bronchodilator FEV1 \\< 80% of predicted normal and post-bronchodilator FEV1 \\< 70% of post-bronchodilator FVC at Visit 1 (according to GOLD criteria).\n\n \\* The randomisation of patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period should be postponed. Patients may be randomised 6 weeks following recovery from the infection or exacerbation. Predicted normal values will be calculated according to ECSC.\n3. Male or female patients 40 years of age or older.\n4. Patients must be current or ex-smokers with a smoking history of 10 pack-years.\n5. Patients must be able to perform technically acceptable pulmonary function tests\n6. Patients must be able to inhale medication in a competent manner.\n7. Patients must be able to perform all necessary recordings in the diary.\n\nExclusion Criteria:\n\n1. Significant diseases other than COPD\n2. Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a significant disease as defined in exclusion criterion No. 1.\n3. Patients with a recent history of myocardial infarction.\n4. Patients with any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the past year.\n5. Hospitalisation for cardiac failure during the past year.\n6. Malignancy within the last five years excluded basal cell carcinoma.\n7. Patients with a history of asthma or who have a total blood eosinophil count 600/mm3.\n8. Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis.\n9. Known active tuberculosis.\n10. Patients with a history of alcohol or drug abuse.\n11. Thoracotomy with pulmonary resection.\n12. Rehabilitation program within the last six weeks\n13. Patients who regularly use daytime oxygen therapy\n14. Patients who have taken an investigational drug within 30 days\n15. Use of not allowed medications\n16. Known hypersensitivity to used drugs or other components of the study medication.\n17. Pregnant or nursing women\n18. Women of childbearing potential not using a highly effective method of birth control. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.\n19. Patients who are currently participating in another study.'}, 'identificationModule': {'nctId': 'NCT00662792', 'briefTitle': 'Efficacy and Safety Comparison of Tiotropium Daily + Salmeterol Daily or Twice Daily Versus Tiotropium Daily in Patients With COPD', 'organization': {'class': 'INDUSTRY', 'fullName': 'Boehringer Ingelheim'}, 'officialTitle': 'A Randomised, Double-blind Clinical Efficacy and Safety Comparison of Tiotropium/Salmeterol 7.5/25 Inhalation Powder in the Morning Via Tiotropium/Salmeterol HandiHaler, Tiotropium 18 Mcg Inhalation Powder in the Morning Via Spiriva HandiHaler, Salmeterol 50 Mcg MDPI in the Morning and Evening and the Free Combination Tiotropium 18 Mcg Inhalation Powder in the Morning Via Spiriva HandiHaler Plus Salmeterol 50 Mcg MDPI in the Morning and Evening Following Chronic Administration (6-week Treatment Periods) in Patients With COPD', 'orgStudyIdInfo': {'id': '1184.13'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI', 'description': '7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE)/ 18 µg Tiotropium (Tio18GEL) / 50 µg Salmeterol MDPI (Salm50DPI) / 18 µg Tiotropium (T18GEL) plus 50 µg Salmeterol MDPI (S\\_DPI) BID', 'interventionNames': ['Drug: Tiotropium (Tio18GEL)', 'Drug: Salmeterol MDPI (Salm50DPI)', 'Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI)', 'Drug: Tiotropium/Salmeterol (T+S_PE)']}, {'type': 'EXPERIMENTAL', 'label': 'Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI', 'description': '18 µg Tiotropium (Tio18GEL) / 18 µg Tiotropium (T18GEL) + 50 µg Salmeterol MDPI (S\\_DPI) BID / 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) / 50 µg Salmeterol MDPI (Salm50DPI)', 'interventionNames': ['Drug: Tiotropium (Tio18GEL)', 'Drug: Salmeterol MDPI (Salm50DPI)', 'Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI)', 'Drug: Tiotropium/Salmeterol (T+S_PE)']}, {'type': 'EXPERIMENTAL', 'label': 'Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL', 'description': '50 µg Salmeterol MDPI (Salm50DPI) / 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) / 18 µg Tiotropium (T18GEL) + 50 µg Salmeterol MDPI (S\\_DPI) BID / 18 µg Tiotropium (Tio18GEL)', 'interventionNames': ['Drug: Tiotropium (Tio18GEL)', 'Drug: Salmeterol MDPI (Salm50DPI)', 'Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI)', 'Drug: Tiotropium/Salmeterol (T+S_PE)']}, {'type': 'EXPERIMENTAL', 'label': 'T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE', 'description': '18 µg Tiotropium (T18GEL) + 50 µg Salmeterol MDPI (S\\_DPI) BID / 50 µg Salmeterol MDPI (Salm50DPI) / 18 µg Tiotropium (Tio18GEL) / 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE)', 'interventionNames': ['Drug: Tiotropium (Tio18GEL)', 'Drug: Salmeterol MDPI (Salm50DPI)', 'Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI)', 'Drug: Tiotropium/Salmeterol (T+S_PE)']}], 'interventions': [{'name': 'Tiotropium (Tio18GEL)', 'type': 'DRUG', 'description': '18 µg Tiotropium (Tio18GEL) inhalation powder', 'armGroupLabels': ['Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL', 'T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI', 'T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE', 'Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI']}, {'name': 'Salmeterol MDPI (Salm50DPI)', 'type': 'DRUG', 'description': '50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID)', 'armGroupLabels': ['Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL', 'T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI', 'T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE', 'Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI']}, {'name': 'Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI)', 'type': 'DRUG', 'description': '18 µg Tiotropium (T18GEL) inhalation powder plus 50 µg Salmeterol MDPI (S\\_DPI) twice daily (BID)', 'armGroupLabels': ['Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL', 'T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI', 'T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE', 'Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI']}, {'name': 'Tiotropium/Salmeterol (T+S_PE)', 'type': 'DRUG', 'description': 'Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\\_PE) inhalation powder', 'armGroupLabels': ['Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL', 'T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI', 'T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE', 'Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Berlin', 'country': 'Germany', 'facility': '1184.13.1302 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 52.52437, 'lon': 13.41053}}, {'city': 'Berlin', 'country': 'Germany', 'facility': '1184.13.1309 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 52.52437, 'lon': 13.41053}}, {'city': 'Cottbus', 'country': 'Germany', 'facility': '1184.13.1308 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 51.75769, 'lon': 14.32888}}, {'city': 'Großhansdorf', 'country': 'Germany', 'facility': '1184.13.1311 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 53.66528, 'lon': 10.28552}}, {'city': 'Hamburg', 'country': 'Germany', 'facility': '1184.13.1312 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 53.55073, 'lon': 9.99302}}, {'city': 'Mainz', 'country': 'Germany', 'facility': '1184.13.1305 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 49.98185, 'lon': 8.28008}}, {'city': 'Mannheim', 'country': 'Germany', 'facility': '1184.13.1301 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 49.4891, 'lon': 8.46694}}, {'city': 'Rodgau-Dudenhofen', 'country': 'Germany', 'facility': '1184.13.1306 Boehringer Ingelheim Investigational Site'}, {'city': 'Rüdersdorf', 'country': 'Germany', 'facility': '1184.13.1310 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 52.46927, 'lon': 13.78631}}, {'city': 'Schwerin', 'country': 'Germany', 'facility': '1184.13.1307 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 53.62937, 'lon': 11.41316}}, {'city': 'Wiesbaden', 'country': 'Germany', 'facility': '1184.13.1304 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 50.08601, 'lon': 8.24435}}, {'city': 'Wiesloch', 'country': 'Germany', 'facility': '1184.13.1303 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 49.29504, 'lon': 8.69846}}], 'overallOfficials': [{'name': 'Boehringer Ingelheim', 'role': 'STUDY_CHAIR', 'affiliation': 'Boehringer Ingelheim'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Boehringer Ingelheim', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}