Ignite Creation Date:
2025-12-25 @ 2:51 AM
Ignite Modification Date:
2025-12-26 @ 1:32 AM
Study NCT ID:
NCT01222533
Status:
COMPLETED
Last Update Posted:
2014-05-16
First Post:
2010-10-15
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Tiotropium Respimat Pharmacokinetic Study in 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'}], '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'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clintriage.rdg@boehringer-ingelheim.com', 'phone': '1-800-243-0127', 'title': 'Boehringer Ingelheim Call Center', 'organization': 'Boehringer Ingelheim Pharmaceuticals'}, 'certainAgreement': {'otherDetails': 'Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': '4 weeks + 30 days if in last period', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler', 'otherNumAtRisk': 147, 'otherNumAffected': 20, 'seriousNumAtRisk': 147, 'seriousNumAffected': 3}, {'id': 'EG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning', 'otherNumAtRisk': 147, 'otherNumAffected': 11, 'seriousNumAtRisk': 147, 'seriousNumAffected': 2}, {'id': 'EG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning', 'otherNumAtRisk': 145, 'otherNumAffected': 4, 'seriousNumAtRisk': 145, 'seriousNumAffected': 0}, {'id': 'EG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning', 'otherNumAtRisk': 150, 'otherNumAffected': 16, 'seriousNumAtRisk': 150, 'seriousNumAffected': 3}, {'id': 'EG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning', 'otherNumAtRisk': 146, 'otherNumAffected': 10, 'seriousNumAtRisk': 146, 'seriousNumAffected': 2}], 'otherEvents': [{'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 9}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 14}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 7}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Dyspnoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 14}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 2}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 3}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 3}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MEDDRA 15.0'}], 'seriousEvents': [{'term': 'Colitis ischaemic', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Haemorrhoidal haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Pancreatitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Infective exacerbation of chronic obstructive airways disease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Tendon rupture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 0}], 'organSystem': 'Injury, poisoning and procedural complications', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Spinal column stenosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Prostate cancer', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 0}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Cerebrovascular accident', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Azotaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 0}], 'organSystem': 'Renal and urinary disorders', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Renal tubular necrosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 0}], 'organSystem': 'Renal and urinary disorders', 'sourceVocabulary': 'MEDDRA 15.0'}, {'term': 'Chronic obstructive pulmonary disease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 147, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 147, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 145, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 150, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 146, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'sourceVocabulary': 'MEDDRA 15.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Maximum Plasma Concentration at Steady-state (Cmax,ss)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '104', 'groupId': 'OG001'}, {'value': '110', 'groupId': 'OG002'}, {'value': '113', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '2.81', 'spread': '53.0', 'groupId': 'OG001'}, {'value': '5.07', 'spread': '61.8', 'groupId': 'OG002'}, {'value': '10.5', 'spread': '66.4', 'groupId': 'OG003'}, {'value': '12.9', 'spread': '64.6', 'groupId': 'OG004'}]}]}], 'analyses': [{'pValue': '0.4423', 'groupIds': ['OG003', 'OG004'], 'paramType': 'Geometric mean ratio (percentage)', 'ciPctValue': '90', 'paramValue': '80.66', 'ciLowerLimit': '73.49', 'ciUpperLimit': '88.52', 'pValueComment': 'Maximum of two one-sided p-values for geometric mean ratio being outside interval 80 percent to 125 percent.', 'dispersionType': 'STANDARD_DEVIATION', 'dispersionValue': '43.4', 'estimateComment': 'Standard deviation is actually the geometric coefficient of variation.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'testedNonInferiority': True, 'nonInferiorityComment': 'The standard bioequivalence range of 80 to 125% was pre-specified for Cmax,ss in order to assess the relative systemic exposure following inhalation of Tio R5 compared to Tio HH18. Bioequivalence was not used as a surrogate for efficacy.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing.', 'description': 'Cmax,ss is the maximum measured concentration of tiotropium in plasma at steady-state.', 'unitOfMeasure': 'pg/ml', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic (PK) Set. This analysis set includes all patients in the treated set who had at least one blood sample drawn or one urine sample collected for PK analysis. Patients with an important protocol violation relevant to the PK population were excluded. No PK data for placebo. All patients with analysable data.'}, {'type': 'PRIMARY', 'title': 'Area Under the Curve 0 to 6 Hours at Steady-state (AUC0-6h,ss)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '22', 'groupId': 'OG001'}, {'value': '76', 'groupId': 'OG002'}, {'value': '107', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '10.0', 'spread': '25.3', 'groupId': 'OG001'}, {'value': '12.8', 'spread': '29.9', 'groupId': 'OG002'}, {'value': '22.1', 'spread': '47.8', 'groupId': 'OG003'}, {'value': '28.4', 'spread': '52.4', 'groupId': 'OG004'}]}]}], 'analyses': [{'pValue': '0.8683', 'groupIds': ['OG003', 'OG004'], 'paramType': 'Geometric mean ratio (percentage)', 'ciPctValue': '90', 'paramValue': '75.99', 'ciLowerLimit': '70.44', 'ciUpperLimit': '81.98', 'pValueComment': 'Maximum of two one-sided p-values for geometric mean ratio being outside interval 80 percent to 125 percent.', 'dispersionType': 'STANDARD_DEVIATION', 'dispersionValue': '34.1', 'estimateComment': 'Standard deviation is actually the geometric coefficient of variation.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'testedNonInferiority': True, 'nonInferiorityComment': 'The standard bioequivalence range of 80 to 125% was pre-specified for AUC0-6,ss in order to assess the relative systemic exposure following inhalation of Tio R5 compared to Tio HH18. Bioequivalence was not used as a surrogate for efficacy.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing.', 'description': 'AUC0-6h,ss is the area under the concentration time curve of tiotropium in plasma over the time interval 0 to 6 hours post-dose at steady-state. AUC0-6h,ss was calculated using the linear up/log down algorithm.', 'unitOfMeasure': 'pg*h/ml', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Set. No PK data for Placebo. The low number of non-missing AUC0-6h,ss results for the Tio R 1.25 and Tio R 2.5 cohorts is due to the exclusion of results below the limit of quantification.'}, {'type': 'SECONDARY', 'title': 'Trough Forced Expiratory Volume in One Second (FEV1) at the End of Each Treatment Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}, {'value': '143', 'groupId': 'OG001'}, {'value': '144', 'groupId': 'OG002'}, {'value': '143', 'groupId': 'OG003'}, {'value': '142', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '1.345', 'spread': '0.045', 'groupId': 'OG000'}, {'value': '1.432', 'spread': '0.045', 'groupId': 'OG001'}, {'value': '1.446', 'spread': '0.045', 'groupId': 'OG002'}, {'value': '1.466', 'spread': '0.045', 'groupId': 'OG003'}, {'value': '1.473', 'spread': '0.045', 'groupId': 'OG004'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.087', 'ciLowerLimit': '0.060', 'ciUpperLimit': '0.114', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.014', 'estimateComment': 'Tio R1.25-Placebo', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.101', 'ciLowerLimit': '0.074', 'ciUpperLimit': '0.128', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.014', 'estimateComment': 'Tio R2.5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.121', 'ciLowerLimit': '0.094', 'ciUpperLimit': '0.148', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.014', 'estimateComment': 'Tio R5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': '4 weeks', 'description': 'Defined as FEV1 measured just prior to the last administration of the morning dose of the randomised treatment. Means are adjusted for sequence, patients within sequences, period and treatment.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set (FAS) with imputed data. FAS includes all patients in the treated set who have analysable data for at least one efficacy endpoint during the relevant crossover period.'}, {'type': 'SECONDARY', 'title': 'FEV1 Area Under the Curve 0 to 6 Hours (AUC0-6h) at the End of Each Treatment Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}, {'value': '143', 'groupId': 'OG001'}, {'value': '144', 'groupId': 'OG002'}, {'value': '143', 'groupId': 'OG003'}, {'value': '142', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '1.371', 'spread': '0.046', 'groupId': 'OG000'}, {'value': '1.535', 'spread': '0.046', 'groupId': 'OG001'}, {'value': '1.556', 'spread': '0.046', 'groupId': 'OG002'}, {'value': '1.562', 'spread': '0.046', 'groupId': 'OG003'}, {'value': '1.567', 'spread': '0.046', 'groupId': 'OG004'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.165', 'ciLowerLimit': '0.141', 'ciUpperLimit': '0.189', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.012', 'estimateComment': 'Tio R1.25-Placebo.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.185', 'ciLowerLimit': '0.161', 'ciUpperLimit': '0.209', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.012', 'estimateComment': 'Tio R2.5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.191', 'ciLowerLimit': '0.167', 'ciUpperLimit': '0.216', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.012', 'estimateComment': 'Tio R5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': '4 weeks', 'description': 'FEV1 AUC0-6h calculated from zero time to 6 hours using the trapezoidal rule divided by 6 hours. Trough FEV1 will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'FAS with imputed data.'}, {'type': 'SECONDARY', 'title': 'FEV1 Area Under the Curve 0 to 3 Hours (AUC0-3h) at the End of Each Treatment Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}, {'value': '143', 'groupId': 'OG001'}, {'value': '144', 'groupId': 'OG002'}, {'value': '143', 'groupId': 'OG003'}, {'value': '142', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '1.366', 'spread': '0.046', 'groupId': 'OG000'}, {'value': '1.521', 'spread': '0.046', 'groupId': 'OG001'}, {'value': '1.546', 'spread': '0.046', 'groupId': 'OG002'}, {'value': '1.553', 'spread': '0.046', 'groupId': 'OG003'}, {'value': '1.558', 'spread': '0.046', 'groupId': 'OG004'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.155', 'ciLowerLimit': '0.130', 'ciUpperLimit': '0.180', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.013', 'estimateComment': 'Tio R1.25-Placebo', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.180', 'ciLowerLimit': '0.155', 'ciUpperLimit': '0.205', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.013', 'estimateComment': 'Tio R2.5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.187', 'ciLowerLimit': '0.162', 'ciUpperLimit': '0.211', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.013', 'estimateComment': 'Tio R5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': '4 weeks', 'description': 'FEV1 AUC0-3h calculated from zero time to 3 hours using the trapezoidal rule divided by 3 hours. Trough FEV1 will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'FAS with imputed data.'}, {'type': 'SECONDARY', 'title': 'Trough Forced Vital Capacity (FVC) at the End of Each Treatment Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '142', 'groupId': 'OG000'}, {'value': '143', 'groupId': 'OG001'}, {'value': '143', 'groupId': 'OG002'}, {'value': '143', 'groupId': 'OG003'}, {'value': '142', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '3.116', 'spread': '0.077', 'groupId': 'OG000'}, {'value': '3.254', 'spread': '0.077', 'groupId': 'OG001'}, {'value': '3.304', 'spread': '0.077', 'groupId': 'OG002'}, {'value': '3.352', 'spread': '0.077', 'groupId': 'OG003'}, {'value': '3.351', 'spread': '0.077', 'groupId': 'OG004'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.138', 'ciLowerLimit': '0.083', 'ciUpperLimit': '0.194', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.028', 'estimateComment': 'Tio R1.25-Placebo', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.188', 'ciLowerLimit': '0.133', 'ciUpperLimit': '0.244', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.028', 'estimateComment': 'Tio R2.5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.236', 'ciLowerLimit': '0.180', 'ciUpperLimit': '0.292', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.028', 'estimateComment': 'Tio R5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': '4 weeks', 'description': 'Defined as the pre-dose FVC measured just prior to the last administration of the morning dose of the randomised treatment. Means are adjusted for sequence, patients within sequences, period and treatment.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'FAS with imputed data. One patient with missing FVC data in Placebo and Tio R2.5 period.'}, {'type': 'SECONDARY', 'title': 'FVC AUC0-6h at the End of Each Treatment Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '142', 'groupId': 'OG000'}, {'value': '143', 'groupId': 'OG001'}, {'value': '143', 'groupId': 'OG002'}, {'value': '143', 'groupId': 'OG003'}, {'value': '142', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '3.153', 'spread': '0.079', 'groupId': 'OG000'}, {'value': '3.436', 'spread': '0.078', 'groupId': 'OG001'}, {'value': '3.472', 'spread': '0.078', 'groupId': 'OG002'}, {'value': '3.488', 'spread': '0.078', 'groupId': 'OG003'}, {'value': '3.483', 'spread': '0.079', 'groupId': 'OG004'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.283', 'ciLowerLimit': '0.241', 'ciUpperLimit': '0.326', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.022', 'estimateComment': 'Tio R1.25-Placebo', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.319', 'ciLowerLimit': '0.276', 'ciUpperLimit': '0.362', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.022', 'estimateComment': 'Tio R2.5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.335', 'ciLowerLimit': '0.292', 'ciUpperLimit': '0.378', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.022', 'estimateComment': 'Tio R5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': '4 weeks', 'description': 'FVC AUC0-6h calculated from zero time to 6 hours using the trapezoidal rule divided by 6 hours. Trough FVC will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'FAS with imputed data. One patient with missing FVC data in Placebo and Tio R2.5 period.'}, {'type': 'SECONDARY', 'title': 'FVC AUC0-3h at the End of Each Treatment Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '142', 'groupId': 'OG000'}, {'value': '143', 'groupId': 'OG001'}, {'value': '143', 'groupId': 'OG002'}, {'value': '143', 'groupId': 'OG003'}, {'value': '142', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '3.140', 'spread': '0.078', 'groupId': 'OG000'}, {'value': '3.421', 'spread': '0.078', 'groupId': 'OG001'}, {'value': '3.465', 'spread': '0.078', 'groupId': 'OG002'}, {'value': '3.479', 'spread': '0.078', 'groupId': 'OG003'}, {'value': '3.480', 'spread': '0.078', 'groupId': 'OG004'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.281', 'ciLowerLimit': '0.236', 'ciUpperLimit': '0.325', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.023', 'estimateComment': 'Tio R1.25-Placebo', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.324', 'ciLowerLimit': '0.279', 'ciUpperLimit': '0.369', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.023', 'estimateComment': 'Tio R2.5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}, {'pValue': '<0.0001', 'groupIds': ['OG000', 'OG003'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.339', 'ciLowerLimit': '0.294', 'ciUpperLimit': '0.384', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.023', 'estimateComment': 'Tio R5-Placebo', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'statisticalComment': 'Adjusted for sequence, patients within sequences, period and treatment.', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': '4 weeks', 'description': 'FVC AUC0-3h calculated from zero time to 3 hours using the trapezoidal rule divided by 3 hours. Trough FVC will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'FAS with imputed data. One patient with missing FVC data in Placebo and Tio R2.5 period.'}, {'type': 'SECONDARY', 'title': 'FEV1 at Each Planned Time at the End of Each Treatment Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '143', 'groupId': 'OG000'}, {'value': '143', 'groupId': 'OG001'}, {'value': '144', 'groupId': 'OG002'}, {'value': '143', 'groupId': 'OG003'}, {'value': '142', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Timepoint 0:00 (trough)', 'categories': [{'measurements': [{'value': '1.349', 'spread': '0.045', 'groupId': 'OG000'}, {'value': '1.436', 'spread': '0.045', 'groupId': 'OG001'}, {'value': '1.450', 'spread': '0.045', 'groupId': 'OG002'}, {'value': '1.470', 'spread': '0.045', 'groupId': 'OG003'}, {'value': '1.477', 'spread': '0.045', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 0:30', 'categories': [{'measurements': [{'value': '1.366', 'spread': '0.046', 'groupId': 'OG000'}, {'value': '1.501', 'spread': '0.046', 'groupId': 'OG001'}, {'value': '1.522', 'spread': '0.046', 'groupId': 'OG002'}, {'value': '1.541', 'spread': '0.046', 'groupId': 'OG003'}, {'value': '1.554', 'spread': '0.046', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 1:00', 'categories': [{'measurements': [{'value': '1.371', 'spread': '0.046', 'groupId': 'OG000'}, {'value': '1.529', 'spread': '0.046', 'groupId': 'OG001'}, {'value': '1.552', 'spread': '0.046', 'groupId': 'OG002'}, {'value': '1.560', 'spread': '0.046', 'groupId': 'OG003'}, {'value': '1.571', 'spread': '0.046', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 2:00', 'categories': [{'measurements': [{'value': '1.375', 'spread': '0.046', 'groupId': 'OG000'}, {'value': '1.543', 'spread': '0.046', 'groupId': 'OG001'}, {'value': '1.573', 'spread': '0.046', 'groupId': 'OG002'}, {'value': '1.572', 'spread': '0.046', 'groupId': 'OG003'}, {'value': '1.571', 'spread': '0.046', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 3:00', 'categories': [{'measurements': [{'value': '1.375', 'spread': '0.047', 'groupId': 'OG000'}, {'value': '1.556', 'spread': '0.047', 'groupId': 'OG001'}, {'value': '1.582', 'spread': '0.047', 'groupId': 'OG002'}, {'value': '1.584', 'spread': '0.047', 'groupId': 'OG003'}, {'value': '1.580', 'spread': '0.047', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 4:00', 'categories': [{'measurements': [{'value': '1.374', 'spread': '0.047', 'groupId': 'OG000'}, {'value': '1.557', 'spread': '0.047', 'groupId': 'OG001'}, {'value': '1.575', 'spread': '0.047', 'groupId': 'OG002'}, {'value': '1.578', 'spread': '0.047', 'groupId': 'OG003'}, {'value': '1.582', 'spread': '0.047', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 5:00', 'categories': [{'measurements': [{'value': '1.394', 'spread': '0.047', 'groupId': 'OG000'}, {'value': '1.562', 'spread': '0.047', 'groupId': 'OG001'}, {'value': '1.571', 'spread': '0.047', 'groupId': 'OG002'}, {'value': '1.579', 'spread': '0.047', 'groupId': 'OG003'}, {'value': '1.588', 'spread': '0.047', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 6:00', 'categories': [{'measurements': [{'value': '1.375', 'spread': '0.047', 'groupId': 'OG000'}, {'value': '1.536', 'spread': '0.048', 'groupId': 'OG001'}, {'value': '1.551', 'spread': '0.047', 'groupId': 'OG002'}, {'value': '1.558', 'spread': '0.047', 'groupId': 'OG003'}, {'value': '1.570', 'spread': '0.048', 'groupId': 'OG004'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks', 'description': 'Means are adjusted for period, planned time, period\\*planned time, patient\\*planned time and patient\\*treatment\\*planned time.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'FAS with imputed data.'}, {'type': 'SECONDARY', 'title': 'FVC at Each Planned Time at the End of Each Treatment Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '142', 'groupId': 'OG000'}, {'value': '143', 'groupId': 'OG001'}, {'value': '143', 'groupId': 'OG002'}, {'value': '143', 'groupId': 'OG003'}, {'value': '142', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Timepoint 0:00 (trough)', 'categories': [{'measurements': [{'value': '3.118', 'spread': '0.076', 'groupId': 'OG000'}, {'value': '3.255', 'spread': '0.076', 'groupId': 'OG001'}, {'value': '3.307', 'spread': '0.076', 'groupId': 'OG002'}, {'value': '3.356', 'spread': '0.076', 'groupId': 'OG003'}, {'value': '3.351', 'spread': '0.076', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 0:30', 'categories': [{'measurements': [{'value': '3.131', 'spread': '0.077', 'groupId': 'OG000'}, {'value': '3.390', 'spread': '0.077', 'groupId': 'OG001'}, {'value': '3.435', 'spread': '0.077', 'groupId': 'OG002'}, {'value': '3.473', 'spread': '0.077', 'groupId': 'OG003'}, {'value': '3.496', 'spread': '0.077', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 1:00', 'categories': [{'measurements': [{'value': '3.152', 'spread': '0.078', 'groupId': 'OG000'}, {'value': '3.449', 'spread': '0.078', 'groupId': 'OG001'}, {'value': '3.484', 'spread': '0.078', 'groupId': 'OG002'}, {'value': '3.488', 'spread': '0.078', 'groupId': 'OG003'}, {'value': '3.499', 'spread': '0.078', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 2:00', 'categories': [{'measurements': [{'value': '3.146', 'spread': '0.078', 'groupId': 'OG000'}, {'value': '3.443', 'spread': '0.078', 'groupId': 'OG001'}, {'value': '3.489', 'spread': '0.078', 'groupId': 'OG002'}, {'value': '3.499', 'spread': '0.078', 'groupId': 'OG003'}, {'value': '3.487', 'spread': '0.078', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 3:00', 'categories': [{'measurements': [{'value': '3.156', 'spread': '0.078', 'groupId': 'OG000'}, {'value': '3.466', 'spread': '0.078', 'groupId': 'OG001'}, {'value': '3.513', 'spread': '0.078', 'groupId': 'OG002'}, {'value': '3.516', 'spread': '0.078', 'groupId': 'OG003'}, {'value': '3.497', 'spread': '0.078', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 4:00', 'categories': [{'measurements': [{'value': '3.161', 'spread': '0.079', 'groupId': 'OG000'}, {'value': '3.468', 'spread': '0.079', 'groupId': 'OG001'}, {'value': '3.495', 'spread': '0.079', 'groupId': 'OG002'}, {'value': '3.505', 'spread': '0.079', 'groupId': 'OG003'}, {'value': '3.501', 'spread': '0.079', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 5:00', 'categories': [{'measurements': [{'value': '3.191', 'spread': '0.079', 'groupId': 'OG000'}, {'value': '3.459', 'spread': '0.079', 'groupId': 'OG001'}, {'value': '3.467', 'spread': '0.079', 'groupId': 'OG002'}, {'value': '3.501', 'spread': '0.079', 'groupId': 'OG003'}, {'value': '3.488', 'spread': '0.079', 'groupId': 'OG004'}]}]}, {'title': 'Timepoint 6:00', 'categories': [{'measurements': [{'value': '3.168', 'spread': '0.079', 'groupId': 'OG000'}, {'value': '3.417', 'spread': '0.079', 'groupId': 'OG001'}, {'value': '3.470', 'spread': '0.079', 'groupId': 'OG002'}, {'value': '3.473', 'spread': '0.079', 'groupId': 'OG003'}, {'value': '3.469', 'spread': '0.079', 'groupId': 'OG004'}]}]}], 'paramType': 'MEAN', 'timeFrame': '4 weeks', 'description': 'Means are adjusted for period, planned time, period\\*planned time, patient\\*planned time and patient\\*treatment\\*planned time.', 'unitOfMeasure': 'Liter', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'FAS with imputed data. One patient with missing FVC data in Placebo and Tio R2.5 period.'}, {'type': 'SECONDARY', 'title': 'Area Under the Curve 0 to 1 Hour at Steady-state (AUC0-1h,ss)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '61', 'groupId': 'OG001'}, {'value': '97', 'groupId': 'OG002'}, {'value': '112', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '2.08', 'spread': '32.3', 'groupId': 'OG001'}, {'value': '3.16', 'spread': '44.4', 'groupId': 'OG002'}, {'value': '6.13', 'spread': '58.3', 'groupId': 'OG003'}, {'value': '7.79', 'spread': '54.9', 'groupId': 'OG004'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing.', 'description': 'AUC0-1h,ss is the area under the concentration time curve of tiotropium in plasma over the time interval 0 to 1 hour post-dose at steady-state. AUC0-1h,ss was calculated using the linear up/log down algorithm.', 'unitOfMeasure': 'pg*h/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Set. All patients with analysable data.'}, {'type': 'SECONDARY', 'title': 'Time to Maximum Plasma Concentration at Steady-state (Tmax,ss)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '104', 'groupId': 'OG001'}, {'value': '110', 'groupId': 'OG002'}, {'value': '113', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '0.100', 'groupId': 'OG001', 'lowerLimit': '0.0330', 'upperLimit': '2.00'}, {'value': '0.0830', 'groupId': 'OG002', 'lowerLimit': '0.0330', 'upperLimit': '6.00'}, {'value': '0.117', 'groupId': 'OG003', 'lowerLimit': '0.0330', 'upperLimit': '0.333'}, {'value': '0.117', 'groupId': 'OG004', 'lowerLimit': '0.0330', 'upperLimit': '1.00'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 min before first dosing of study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 h, 2 h, 4 h and 6 h post dosing.', 'description': 'Tmax,ss is the time from dosing to the maximum concentration of tiotropium in plasma-venous blood at steady-state.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Set. All patients with analysable data.'}, {'type': 'SECONDARY', 'title': 'Amount of Drug Eliminated in Urine at Steady-state (Ae0-6h,ss)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '108', 'groupId': 'OG001'}, {'value': '110', 'groupId': 'OG002'}, {'value': '107', 'groupId': 'OG003'}, {'value': '109', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '88.7', 'spread': '68.0', 'groupId': 'OG001'}, {'value': '177', 'spread': '68.0', 'groupId': 'OG002'}, {'value': '387', 'spread': '65.9', 'groupId': 'OG003'}, {'value': '522', 'spread': '53.8', 'groupId': 'OG004'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Based on urine sampling for PK assessments done at 4 weeks in the following intervals: -1 to 0 hour (h), 0 to 2 h and 2 to 6 h post-dosing.', 'description': 'Total quantity of the analyte that is excreted in urine over the time interval 0 to 6 hours at steady state.', 'unitOfMeasure': 'ng', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Set. All patients with analysable data.'}, {'type': 'SECONDARY', 'title': 'Pre-dose Plasma Concentration at Steady-state (Cpre,ss)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}, {'value': '19', 'groupId': 'OG002'}, {'value': '74', 'groupId': 'OG003'}, {'value': '85', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '1.57', 'spread': '43.1', 'groupId': 'OG001'}, {'value': '1.39', 'spread': '22.8', 'groupId': 'OG002'}, {'value': '1.60', 'spread': '35.8', 'groupId': 'OG003'}, {'value': '1.71', 'spread': '42.5', 'groupId': 'OG004'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time point: 5 minutes (min) before first dosing of study drug (baseline)', 'description': 'Cpre,ss is the measured concentration of tiotropium in plasma before dosing at steady-state.', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Set. All patients with analysable data.'}, {'type': 'SECONDARY', 'title': 'Renal Clearance at Steady-state (CL R,0-6h,ss)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '22', 'groupId': 'OG001'}, {'value': '75', 'groupId': 'OG002'}, {'value': '102', 'groupId': 'OG003'}, {'value': '109', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '256', 'spread': '32.1', 'groupId': 'OG001'}, {'value': '277', 'spread': '55.8', 'groupId': 'OG002'}, {'value': '307', 'spread': '39.6', 'groupId': 'OG003'}, {'value': '310', 'spread': '40.4', 'groupId': 'OG004'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Based on blood and urine sampling for PK assessments done at 4 weeks over 6 h post dosing.', 'description': 'Renal clearance of the drug over the time interval 0 to 6 hours at steady-state. CL R,0-6h,ss was calculated as the quotient of Ae0-6h,ss and AUC0-6h,ss.', 'unitOfMeasure': 'mL/min', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Set. All patients with analysable data.'}, {'type': 'SECONDARY', 'title': 'Minimum Plasma Concentration at Steady-state (Cmin,ss)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '103', 'groupId': 'OG001'}, {'value': '110', 'groupId': 'OG002'}, {'value': '113', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'categories': [{'measurements': [{'value': '1.16', 'spread': '14.5', 'groupId': 'OG001'}, {'value': '1.25', 'spread': '17.7', 'groupId': 'OG002'}, {'value': '1.57', 'spread': '32.3', 'groupId': 'OG003'}, {'value': '1.76', 'spread': '42.3', 'groupId': 'OG004'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 min before first dosing of study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 h, 2 h, 4 h and 6 h post dosing.', 'description': 'Cmin,ss is the minimum measured concentration of tiotropium in plasma at steady-state.', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Set. All patients with analysable data.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Maximum Heart Rate (HR)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '115', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}, {'value': '115', 'groupId': 'OG002'}, {'value': '116', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Day 29 6.5 h(N=115,115,115,116,113)', 'categories': [{'measurements': [{'value': '109.29', 'spread': '15.23', 'groupId': 'OG000'}, {'value': '109.57', 'spread': '15.29', 'groupId': 'OG001'}, {'value': '109.93', 'spread': '15.47', 'groupId': 'OG002'}, {'value': '109.34', 'spread': '14.36', 'groupId': 'OG003'}, {'value': '108.68', 'spread': '14.28', 'groupId': 'OG004'}]}]}, {'title': 'Day 29 1st h(N=114,113,115,115,111)', 'categories': [{'measurements': [{'value': '97.83', 'spread': '13.65', 'groupId': 'OG000'}, {'value': '99.20', 'spread': '14.65', 'groupId': 'OG001'}, {'value': '98.43', 'spread': '14.68', 'groupId': 'OG002'}, {'value': '97.16', 'spread': '13.97', 'groupId': 'OG003'}, {'value': '97.33', 'spread': '13.00', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 6.5 h(N=115,110,113,110,112)', 'categories': [{'measurements': [{'value': '108.35', 'spread': '16.32', 'groupId': 'OG000'}, {'value': '107.37', 'spread': '14.04', 'groupId': 'OG001'}, {'value': '108.90', 'spread': '15.85', 'groupId': 'OG002'}, {'value': '107.65', 'spread': '16.37', 'groupId': 'OG003'}, {'value': '109.57', 'spread': '14.70', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 1st h(N=115,109,113,107,109)', 'categories': [{'measurements': [{'value': '91.73', 'spread': '12.44', 'groupId': 'OG000'}, {'value': '91.51', 'spread': '12.87', 'groupId': 'OG001'}, {'value': '92.59', 'spread': '15.40', 'groupId': 'OG002'}, {'value': '91.60', 'spread': '12.07', 'groupId': 'OG003'}, {'value': '92.74', 'spread': '12.75', 'groupId': 'OG004'}]}]}], 'paramType': 'MEAN', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'Maximum HR evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.', 'unitOfMeasure': 'bpm', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'ECGFAS - including all patients in the treated set for whom continuous 12 lead ECGs (Holter monitoring) were recorded on at least one occasion (pacemaker patients were excluded).'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Mean Heart Rate (HR)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '115', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}, {'value': '115', 'groupId': 'OG002'}, {'value': '116', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Day 29 6.5 h(N=115,115,115,116,113)', 'categories': [{'measurements': [{'value': '76.97', 'spread': '10.39', 'groupId': 'OG000'}, {'value': '76.37', 'spread': '10.69', 'groupId': 'OG001'}, {'value': '77.75', 'spread': '10.95', 'groupId': 'OG002'}, {'value': '76.87', 'spread': '10.82', 'groupId': 'OG003'}, {'value': '77.31', 'spread': '10.45', 'groupId': 'OG004'}]}]}, {'title': 'Day 29 1st h(N=114,113,115,115,111)', 'categories': [{'measurements': [{'value': '73.87', 'spread': '10.07', 'groupId': 'OG000'}, {'value': '73.76', 'spread': '10.60', 'groupId': 'OG001'}, {'value': '74.39', 'spread': '10.82', 'groupId': 'OG002'}, {'value': '73.82', 'spread': '11.06', 'groupId': 'OG003'}, {'value': '73.71', 'spread': '9.80', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 6.5 h(N=115,110,113,110,112)', 'categories': [{'measurements': [{'value': '75.76', 'spread': '10.88', 'groupId': 'OG000'}, {'value': '75.00', 'spread': '10.87', 'groupId': 'OG001'}, {'value': '76.25', 'spread': '12.00', 'groupId': 'OG002'}, {'value': '75.35', 'spread': '10.86', 'groupId': 'OG003'}, {'value': '75.81', 'spread': '10.39', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 1st h(N=115,109,113,107,109)', 'categories': [{'measurements': [{'value': '70.75', 'spread': '10.20', 'groupId': 'OG000'}, {'value': '70.33', 'spread': '10.66', 'groupId': 'OG001'}, {'value': '71.11', 'spread': '11.93', 'groupId': 'OG002'}, {'value': '70.67', 'spread': '10.77', 'groupId': 'OG003'}, {'value': '70.21', 'spread': '9.58', 'groupId': 'OG004'}]}]}], 'paramType': 'MEAN', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'Mean HR evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.', 'unitOfMeasure': 'bpm', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'ECGFAS - including all patients in the treated set for whom continuous 12 lead ECGs (Holter monitoring) were recorded on at least one occasion (pacemaker patients were excluded)'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'SVPB Total', 'denoms': [{'units': 'Participants', 'counts': [{'value': '115', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}, {'value': '115', 'groupId': 'OG002'}, {'value': '116', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Day 29 6.5 h', 'categories': [{'measurements': [{'value': '109', 'groupId': 'OG000'}, {'value': '112', 'groupId': 'OG001'}, {'value': '109', 'groupId': 'OG002'}, {'value': '108', 'groupId': 'OG003'}, {'value': '107', 'groupId': 'OG004'}]}]}, {'title': 'Day 29 1st h', 'categories': [{'measurements': [{'value': '83', 'groupId': 'OG000'}, {'value': '79', 'groupId': 'OG001'}, {'value': '75', 'groupId': 'OG002'}, {'value': '84', 'groupId': 'OG003'}, {'value': '75', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 6.5 h', 'categories': [{'measurements': [{'value': '111', 'groupId': 'OG000'}, {'value': '103', 'groupId': 'OG001'}, {'value': '106', 'groupId': 'OG002'}, {'value': '98', 'groupId': 'OG003'}, {'value': '105', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 1st h', 'categories': [{'measurements': [{'value': '82', 'groupId': 'OG000'}, {'value': '74', 'groupId': 'OG001'}, {'value': '75', 'groupId': 'OG002'}, {'value': '62', 'groupId': 'OG003'}, {'value': '66', 'groupId': 'OG004'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) event evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'ECGFAS - including all patients in the treated set for whom continuous 12 lead ECGs (Holter monitoring) were recorded on at least one occasion (pacemaker patients were excluded)'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'SVPB Runs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '115', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}, {'value': '115', 'groupId': 'OG002'}, {'value': '116', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Day 29 6.5 h', 'categories': [{'measurements': [{'value': '47', 'groupId': 'OG000'}, {'value': '36', 'groupId': 'OG001'}, {'value': '44', 'groupId': 'OG002'}, {'value': '34', 'groupId': 'OG003'}, {'value': '39', 'groupId': 'OG004'}]}]}, {'title': 'Day 29 1st h', 'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}, {'value': '16', 'groupId': 'OG001'}, {'value': '8', 'groupId': 'OG002'}, {'value': '5', 'groupId': 'OG003'}, {'value': '6', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 6.5 h', 'categories': [{'measurements': [{'value': '35', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}, {'value': '29', 'groupId': 'OG002'}, {'value': '36', 'groupId': 'OG003'}, {'value': '34', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 1st h', 'categories': [{'measurements': [{'value': '12', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '9', 'groupId': 'OG002'}, {'value': '11', 'groupId': 'OG003'}, {'value': '10', 'groupId': 'OG004'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) run evaluated over the entire 6.5 h Holter monitoring period. Runs were defined as at least 3 premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'ECGFAS - including all patients in the treated set for whom continuous 12 lead ECGs (Holter monitoring) were recorded on at least one occasion (pacemaker patients were excluded)'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'SVPB Pairs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '115', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}, {'value': '115', 'groupId': 'OG002'}, {'value': '116', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Day 29 6.5 h', 'categories': [{'measurements': [{'value': '48', 'groupId': 'OG000'}, {'value': '52', 'groupId': 'OG001'}, {'value': '55', 'groupId': 'OG002'}, {'value': '49', 'groupId': 'OG003'}, {'value': '53', 'groupId': 'OG004'}]}]}, {'title': 'Day 29 1st h', 'categories': [{'measurements': [{'value': '17', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}, {'value': '19', 'groupId': 'OG002'}, {'value': '20', 'groupId': 'OG003'}, {'value': '16', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 6.5 h', 'categories': [{'measurements': [{'value': '41', 'groupId': 'OG000'}, {'value': '46', 'groupId': 'OG001'}, {'value': '29', 'groupId': 'OG002'}, {'value': '42', 'groupId': 'OG003'}, {'value': '45', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 1st h', 'categories': [{'measurements': [{'value': '18', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}, {'value': '10', 'groupId': 'OG002'}, {'value': '14', 'groupId': 'OG003'}, {'value': '13', 'groupId': 'OG004'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) pair evaluated over the entire 6.5 h Holter monitoring period. Pairs were defined as 2 consecutive premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'ECGFAS - including all patients in the treated set for whom continuous 12 lead ECGs (Holter monitoring) were recorded on at least one occasion (pacemaker patients were excluded)'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'SVPB Singles', 'denoms': [{'units': 'Participants', 'counts': [{'value': '115', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}, {'value': '115', 'groupId': 'OG002'}, {'value': '116', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Day 29 6.5 h', 'categories': [{'measurements': [{'value': '109', 'groupId': 'OG000'}, {'value': '112', 'groupId': 'OG001'}, {'value': '109', 'groupId': 'OG002'}, {'value': '108', 'groupId': 'OG003'}, {'value': '107', 'groupId': 'OG004'}]}]}, {'title': 'Day 29 1st h', 'categories': [{'measurements': [{'value': '82', 'groupId': 'OG000'}, {'value': '77', 'groupId': 'OG001'}, {'value': '72', 'groupId': 'OG002'}, {'value': '82', 'groupId': 'OG003'}, {'value': '73', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 6.5 h', 'categories': [{'measurements': [{'value': '111', 'groupId': 'OG000'}, {'value': '102', 'groupId': 'OG001'}, {'value': '106', 'groupId': 'OG002'}, {'value': '98', 'groupId': 'OG003'}, {'value': '105', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 1st h', 'categories': [{'measurements': [{'value': '78', 'groupId': 'OG000'}, {'value': '74', 'groupId': 'OG001'}, {'value': '74', 'groupId': 'OG002'}, {'value': '61', 'groupId': 'OG003'}, {'value': '64', 'groupId': 'OG004'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) single evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'ECGFAS - including all patients in the treated set for whom continuous 12 lead ECGs (Holter monitoring) were recorded on at least one occasion (pacemaker patients were excluded)'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'VPB Total', 'denoms': [{'units': 'Participants', 'counts': [{'value': '115', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}, {'value': '115', 'groupId': 'OG002'}, {'value': '116', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Day 29 6.5 h', 'categories': [{'measurements': [{'value': '91', 'groupId': 'OG000'}, {'value': '99', 'groupId': 'OG001'}, {'value': '90', 'groupId': 'OG002'}, {'value': '96', 'groupId': 'OG003'}, {'value': '96', 'groupId': 'OG004'}]}]}, {'title': 'Day 29 1st h', 'categories': [{'measurements': [{'value': '59', 'groupId': 'OG000'}, {'value': '63', 'groupId': 'OG001'}, {'value': '58', 'groupId': 'OG002'}, {'value': '50', 'groupId': 'OG003'}, {'value': '59', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 6.5 h', 'categories': [{'measurements': [{'value': '92', 'groupId': 'OG000'}, {'value': '82', 'groupId': 'OG001'}, {'value': '83', 'groupId': 'OG002'}, {'value': '89', 'groupId': 'OG003'}, {'value': '88', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 1st h', 'categories': [{'measurements': [{'value': '59', 'groupId': 'OG000'}, {'value': '49', 'groupId': 'OG001'}, {'value': '49', 'groupId': 'OG002'}, {'value': '49', 'groupId': 'OG003'}, {'value': '56', 'groupId': 'OG004'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) event evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'ECGFAS - including all patients in the treated set for whom continuous 12 lead ECGs (Holter monitoring) were recorded on at least one occasion (pacemaker patients were excluded)'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'VPB Runs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '115', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}, {'value': '115', 'groupId': 'OG002'}, {'value': '116', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Day 29 6.5 h', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}, {'value': '4', 'groupId': 'OG002'}, {'value': '10', 'groupId': 'OG003'}, {'value': '9', 'groupId': 'OG004'}]}]}, {'title': 'Day 29 1st h', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}, {'value': '2', 'groupId': 'OG002'}, {'value': '2', 'groupId': 'OG003'}, {'value': '1', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 6.5 h', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}, {'value': '8', 'groupId': 'OG002'}, {'value': '9', 'groupId': 'OG003'}, {'value': '9', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 1st h', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}, {'value': '1', 'groupId': 'OG002'}, {'value': '4', 'groupId': 'OG003'}, {'value': '3', 'groupId': 'OG004'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) run evaluated over the entire 6.5 h Holter monitoring period. Runs were defined as at least 3 premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'ECGFAS - including all patients in the treated set for whom continuous 12 lead ECGs (Holter monitoring) were recorded on at least one occasion (pacemaker patients were excluded)'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'VPB Pairs', 'denoms': [{'units': 'Participants', 'counts': [{'value': '115', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}, {'value': '115', 'groupId': 'OG002'}, {'value': '116', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Day 29 6.5 h', 'categories': [{'measurements': [{'value': '24', 'groupId': 'OG000'}, {'value': '19', 'groupId': 'OG001'}, {'value': '21', 'groupId': 'OG002'}, {'value': '16', 'groupId': 'OG003'}, {'value': '22', 'groupId': 'OG004'}]}]}, {'title': 'Day 29 1st h', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}, {'value': '6', 'groupId': 'OG002'}, {'value': '6', 'groupId': 'OG003'}, {'value': '7', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 6.5 h', 'categories': [{'measurements': [{'value': '24', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}, {'value': '19', 'groupId': 'OG002'}, {'value': '21', 'groupId': 'OG003'}, {'value': '22', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 1st h', 'categories': [{'measurements': [{'value': '7', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}, {'value': '7', 'groupId': 'OG002'}, {'value': '6', 'groupId': 'OG003'}, {'value': '10', 'groupId': 'OG004'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) pair evaluated over the entire 6.5 h Holter monitoring period. Pairs were defined as 2 consecutive premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'ECGFAS - including all patients in the treated set for whom continuous 12 lead ECGs (Holter monitoring) were recorded on at least one occasion (pacemaker patients were excluded)'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'VPB Singles', 'denoms': [{'units': 'Participants', 'counts': [{'value': '115', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}, {'value': '115', 'groupId': 'OG002'}, {'value': '116', 'groupId': 'OG003'}, {'value': '113', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Matching Placebo once daily (qd) delivered by the Respimat inhaler'}, {'id': 'OG001', 'title': 'Tio R1.25', 'description': 'Tiotropium inhalation solution 1.25 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG002', 'title': 'Tio R2.5', 'description': 'Tiotropium inhalation solution 2.5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG003', 'title': 'Tio R5', 'description': 'Tiotropium inhalation solution 5 mcg delivered by the Respimat inhaler qd in the morning'}, {'id': 'OG004', 'title': 'Tio HH18', 'description': 'Open-label tiotropium inhalation capsule 18 mcg delivered by the HandiHaler qd in the morning'}], 'classes': [{'title': 'Day 29 6.5 h', 'categories': [{'measurements': [{'value': '91', 'groupId': 'OG000'}, {'value': '99', 'groupId': 'OG001'}, {'value': '89', 'groupId': 'OG002'}, {'value': '94', 'groupId': 'OG003'}, {'value': '96', 'groupId': 'OG004'}]}]}, {'title': 'Day 29 1st h', 'categories': [{'measurements': [{'value': '59', 'groupId': 'OG000'}, {'value': '63', 'groupId': 'OG001'}, {'value': '58', 'groupId': 'OG002'}, {'value': '50', 'groupId': 'OG003'}, {'value': '58', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 6.5 h', 'categories': [{'measurements': [{'value': '92', 'groupId': 'OG000'}, {'value': '82', 'groupId': 'OG001'}, {'value': '81', 'groupId': 'OG002'}, {'value': '88', 'groupId': 'OG003'}, {'value': '88', 'groupId': 'OG004'}]}]}, {'title': 'Day 26 1st h', 'categories': [{'measurements': [{'value': '59', 'groupId': 'OG000'}, {'value': '49', 'groupId': 'OG001'}, {'value': '48', 'groupId': 'OG002'}, {'value': '49', 'groupId': 'OG003'}, {'value': '55', 'groupId': 'OG004'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) single evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'ECGFAS - including all patients in the treated set for whom continuous 12 lead ECGs (Holter monitoring) were recorded on at least one occasion (pacemaker patients were excluded)'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Study Overall', 'description': 'Total number of patients randomised and treated in the study. This was a randomised 5-period crossover trial. 154 patients were randomised to one of 15 sequences and treated. The trial was blinded within the 4 Respimat treatments, but open for the HandiHaler treatment. Each of the 5 treatment regimens was taken for 4 weeks without washouts between treatment periods.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': 'Entered and treated.', 'groupId': 'FG000', 'numSubjects': '154'}]}, {'type': 'Received Placebo', 'achievements': [{'groupId': 'FG000', 'numSubjects': '147'}]}, {'type': 'Received Tio R1.25', 'achievements': [{'groupId': 'FG000', 'numSubjects': '147'}]}, {'type': 'Received Tio R2.5', 'achievements': [{'groupId': 'FG000', 'numSubjects': '145'}]}, {'type': 'Received Tio R5', 'achievements': [{'groupId': 'FG000', 'numSubjects': '150'}]}, {'type': 'Received Tio HH18', 'achievements': [{'groupId': 'FG000', 'numSubjects': '146'}]}, {'type': 'COMPLETED', 'achievements': [{'comment': 'Completed planned observation time (week 21)', 'groupId': 'FG000', 'numSubjects': '140'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '14'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '5'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '5'}]}, {'type': 'Other', 'reasons': [{'groupId': 'FG000', 'numSubjects': '4'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '154', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Study Overall', 'description': 'Total number of patients randomised and treated in the study.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '63.1', 'spread': '7.8', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '37', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '117', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 154}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-08', 'lastUpdateSubmitDate': '2014-05-07', 'studyFirstSubmitDate': '2010-10-15', 'resultsFirstSubmitDate': '2012-11-13', 'studyFirstSubmitQcDate': '2010-10-15', 'lastUpdatePostDateStruct': {'date': '2014-05-16', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2012-11-13', 'studyFirstPostDateStruct': {'date': '2010-10-18', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2012-12-10', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Maximum Heart Rate (HR)', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'Maximum HR evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.'}, {'measure': 'Mean Heart Rate (HR)', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'Mean HR evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.'}, {'measure': 'SVPB Total', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) event evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.'}, {'measure': 'SVPB Runs', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) run evaluated over the entire 6.5 h Holter monitoring period. Runs were defined as at least 3 premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.'}, {'measure': 'SVPB Pairs', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) pair evaluated over the entire 6.5 h Holter monitoring period. Pairs were defined as 2 consecutive premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.'}, {'measure': 'SVPB Singles', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Supraventricular Premature Beat (SVPB) single evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.'}, {'measure': 'VPB Total', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) event evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.'}, {'measure': 'VPB Runs', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) run evaluated over the entire 6.5 h Holter monitoring period. Runs were defined as at least 3 premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.'}, {'measure': 'VPB Pairs', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) pair evaluated over the entire 6.5 h Holter monitoring period. Pairs were defined as 2 consecutive premature beats in a row. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.'}, {'measure': 'VPB Singles', 'timeFrame': '6.5 hours (including pre dose)', 'description': 'The outcome measure describes the number of patients with a Ventricular Premature Beat (VPB) single evaluated over the entire 6.5 h Holter monitoring period. The arrhythmia variables were pre-specified for day 29 and analysed post-hoc for day 26. The lines "Day 29 1st h" and "Day 26 1st h" are related to the interval 0 h to 1 h, i.e. the first hour after dosing.'}], 'primaryOutcomes': [{'measure': 'Maximum Plasma Concentration at Steady-state (Cmax,ss)', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing.', 'description': 'Cmax,ss is the maximum measured concentration of tiotropium in plasma at steady-state.'}, {'measure': 'Area Under the Curve 0 to 6 Hours at Steady-state (AUC0-6h,ss)', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing.', 'description': 'AUC0-6h,ss is the area under the concentration time curve of tiotropium in plasma over the time interval 0 to 6 hours post-dose at steady-state. AUC0-6h,ss was calculated using the linear up/log down algorithm.'}], 'secondaryOutcomes': [{'measure': 'Trough Forced Expiratory Volume in One Second (FEV1) at the End of Each Treatment Period', 'timeFrame': '4 weeks', 'description': 'Defined as FEV1 measured just prior to the last administration of the morning dose of the randomised treatment. Means are adjusted for sequence, patients within sequences, period and treatment.'}, {'measure': 'FEV1 Area Under the Curve 0 to 6 Hours (AUC0-6h) at the End of Each Treatment Period', 'timeFrame': '4 weeks', 'description': 'FEV1 AUC0-6h calculated from zero time to 6 hours using the trapezoidal rule divided by 6 hours. Trough FEV1 will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.'}, {'measure': 'FEV1 Area Under the Curve 0 to 3 Hours (AUC0-3h) at the End of Each Treatment Period', 'timeFrame': '4 weeks', 'description': 'FEV1 AUC0-3h calculated from zero time to 3 hours using the trapezoidal rule divided by 3 hours. Trough FEV1 will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.'}, {'measure': 'Trough Forced Vital Capacity (FVC) at the End of Each Treatment Period', 'timeFrame': '4 weeks', 'description': 'Defined as the pre-dose FVC measured just prior to the last administration of the morning dose of the randomised treatment. Means are adjusted for sequence, patients within sequences, period and treatment.'}, {'measure': 'FVC AUC0-6h at the End of Each Treatment Period', 'timeFrame': '4 weeks', 'description': 'FVC AUC0-6h calculated from zero time to 6 hours using the trapezoidal rule divided by 6 hours. Trough FVC will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.'}, {'measure': 'FVC AUC0-3h at the End of Each Treatment Period', 'timeFrame': '4 weeks', 'description': 'FVC AUC0-3h calculated from zero time to 3 hours using the trapezoidal rule divided by 3 hours. Trough FVC will be assigned to zero time. Means are adjusted for sequence, patients within sequences, period and treatment.'}, {'measure': 'FEV1 at Each Planned Time at the End of Each Treatment Period', 'timeFrame': '4 weeks', 'description': 'Means are adjusted for period, planned time, period\\*planned time, patient\\*planned time and patient\\*treatment\\*planned time.'}, {'measure': 'FVC at Each Planned Time at the End of Each Treatment Period', 'timeFrame': '4 weeks', 'description': 'Means are adjusted for period, planned time, period\\*planned time, patient\\*planned time and patient\\*treatment\\*planned time.'}, {'measure': 'Area Under the Curve 0 to 1 Hour at Steady-state (AUC0-1h,ss)', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing.', 'description': 'AUC0-1h,ss is the area under the concentration time curve of tiotropium in plasma over the time interval 0 to 1 hour post-dose at steady-state. AUC0-1h,ss was calculated using the linear up/log down algorithm.'}, {'measure': 'Time to Maximum Plasma Concentration at Steady-state (Tmax,ss)', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 min before first dosing of study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 h, 2 h, 4 h and 6 h post dosing.', 'description': 'Tmax,ss is the time from dosing to the maximum concentration of tiotropium in plasma-venous blood at steady-state.'}, {'measure': 'Amount of Drug Eliminated in Urine at Steady-state (Ae0-6h,ss)', 'timeFrame': 'Based on urine sampling for PK assessments done at 4 weeks in the following intervals: -1 to 0 hour (h), 0 to 2 h and 2 to 6 h post-dosing.', 'description': 'Total quantity of the analyte that is excreted in urine over the time interval 0 to 6 hours at steady state.'}, {'measure': 'Pre-dose Plasma Concentration at Steady-state (Cpre,ss)', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time point: 5 minutes (min) before first dosing of study drug (baseline)', 'description': 'Cpre,ss is the measured concentration of tiotropium in plasma before dosing at steady-state.'}, {'measure': 'Renal Clearance at Steady-state (CL R,0-6h,ss)', 'timeFrame': 'Based on blood and urine sampling for PK assessments done at 4 weeks over 6 h post dosing.', 'description': 'Renal clearance of the drug over the time interval 0 to 6 hours at steady-state. CL R,0-6h,ss was calculated as the quotient of Ae0-6h,ss and AUC0-6h,ss.'}, {'measure': 'Minimum Plasma Concentration at Steady-state (Cmin,ss)', 'timeFrame': 'Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 min before first dosing of study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 h, 2 h, 4 h and 6 h post dosing.', 'description': 'Cmin,ss is the minimum measured concentration of tiotropium in plasma at steady-state.'}]}, 'conditionsModule': {'conditions': ['Pulmonary Disease, Chronic Obstructive']}, 'referencesModule': {'references': [{'pmid': '25496316', 'type': 'DERIVED', 'citation': 'Hohlfeld JM, Furtwaengler A, Konen-Bergmann M, Wallenstein G, Walter B, Bateman ED. Cardiac safety of tiotropium in patients with COPD: a combined analysis of Holter-ECG data from four randomised clinical trials. Int J Clin Pract. 2015 Jan;69(1):72-80. doi: 10.1111/ijcp.12596. Epub 2014 Dec 11.'}, {'pmid': '24165906', 'type': 'DERIVED', 'citation': 'Hohlfeld JM, Sharma A, van Noord JA, Cornelissen PJ, Derom E, Towse L, Peterkin V, Disse B. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014 Apr;54(4):405-14. doi: 10.1002/jcph.215. Epub 2013 Nov 27.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is compare the effect of different doses of tiotropium delivered by the HandiHaler and Respimat device on lung function. Additionally, the study will investigate the pharmacokinetic profile of these different doses. Studying the pharmacokinetic profile shows what happens to the medication in the body over a period of hours and provides information on potential effects of the medication.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '40 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion criteria:\n\n1. All patient must sign an informed consent consistent with IInternational Conference on Harmonisation- Good Clinical Practice (ICH-GCP) guidelines and local legislation prior to any study-related procedures, including medication washout and restrictions.\n2. Relatively stable, moderate to very severe Chronic Obstructive Pulmonary Disease (COPD)\n3. Current or ex-smokers (smoking history of at least 10 pack years)\n4. Able to perform lung function tests\n5. Able to use study inhalers\n\nExclusion criteria:\n\n1. Significant diseases other than COPD\n2. Recent myocardial infarction, unstable or life-threatening cardiac arrhythmia, hospitalisation for cardiac failure.\n3. Malignancy requiring resection, radiation therapy or chemotherapy within the last 5 years\n4. History of asthma, life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis 5 Active tuberculosis\n\n6\\. History of alcohol or drug abuse 7. Pulmonary resection 8. Recent completion of a pulmonary rehabilitation program or current participation which will not be continued 9. Daytime oxygen therapy for more than 1 hour per day. 10. Use of other investigational drugs, restrictions on the use of some respiratory medications during the study period.\n\n11\\. Current participation in another clinical trial 12. Pregnant or nursing women 13. Women of childbearing potential not using a highly effective method of contraception (e.g: implants, injectable, oral contraceptives)'}, 'identificationModule': {'nctId': 'NCT01222533', 'briefTitle': 'Tiotropium Respimat Pharmacokinetic Study in COPD', 'organization': {'class': 'INDUSTRY', 'fullName': 'Boehringer Ingelheim'}, 'officialTitle': 'A Multicenter, Randomised, Placebo- and Active-controlled, 5 Way, Crossover Trial to Characterise the Pharmacokinetics and Evaluate the Bronchodilator Efficacy and Safety of Once-daily Tiotropium Delivered (Double-blind) From the Respimat Inhaler as Solution for Inhalation (1.25, 2.5, 5 mcg or Placebo) and as Inhalation Powder (18mcg) From the HandiHaler (Open Label) After 4 Week-treatment Periods in Patients With Chronic Obstructive Pulmonary Disease (COPD)', 'orgStudyIdInfo': {'id': '205.458'}, 'secondaryIdInfos': [{'id': '2009-016251-21', 'type': 'EUDRACT_NUMBER', 'domain': 'EudraCT'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Tiotropium low', 'description': 'Tiotropium inhalation solution low dose', 'interventionNames': ['Drug: Tiotropium low']}, {'type': 'EXPERIMENTAL', 'label': 'Tiotropium medium', 'description': 'Tiotropium inhalation solution medium dose', 'interventionNames': ['Drug: Tiotropium medium']}, {'type': 'EXPERIMENTAL', 'label': 'Tiotropium high', 'description': 'Tiotropium inhalation solution high dose', 'interventionNames': ['Drug: Tiotropium high']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Tiotropium 18mcg', 'description': 'Tiotropium inhalation powder 18mcg', 'interventionNames': ['Drug: Tiotropium 18mcg']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Tiotropium placebo', 'description': 'Placebo inhalation solution', 'interventionNames': ['Drug: Tiotropium placebo']}], 'interventions': [{'name': 'Tiotropium medium', 'type': 'DRUG', 'description': 'Tiotropium inhalation solution medium dose', 'armGroupLabels': ['Tiotropium medium']}, {'name': 'Tiotropium low', 'type': 'DRUG', 'description': 'Tiotropium inhalation solution low dose', 'armGroupLabels': ['Tiotropium low']}, {'name': 'Tiotropium high', 'type': 'DRUG', 'description': 'Tiotropium inhalation solution high dose', 'armGroupLabels': ['Tiotropium high']}, {'name': 'Tiotropium 18mcg', 'type': 'DRUG', 'description': 'Tiotropium inhalation powder 18mcg', 'armGroupLabels': ['Tiotropium 18mcg']}, {'name': 'Tiotropium placebo', 'type': 'DRUG', 'description': 'Placebo inhalation solution', 'armGroupLabels': ['Tiotropium placebo']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Genk', 'country': 'Belgium', 'facility': '205.458.32003 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 50.965, 'lon': 5.50082}}, {'city': 'Ghent', 'country': 'Belgium', 'facility': '205.458.32001 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 51.05, 'lon': 3.71667}}, {'city': 'Hasselt', 'country': 'Belgium', 'facility': '205.458.32002 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 50.93106, 'lon': 5.33781}}, {'city': 'Copenhagen K', 'country': 'Denmark', 'facility': '205.458.45001 Boehringer Ingelheim Investigational Site'}, {'city': 'København NV', 'country': 'Denmark', 'facility': '205.458.45003 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 55.71258, 'lon': 12.52343}}, {'city': 'Odense C', 'country': 'Denmark', 'facility': '205.458.45002 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 55.40841, 'lon': 10.39538}}, {'city': 'Helsinki', 'country': 'Finland', 'facility': '205.458.35801 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 60.16952, 'lon': 24.93545}}, {'city': 'Tampere', 'country': 'Finland', 'facility': '205.458.35802 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 61.49911, 'lon': 23.78712}}, {'city': 'Hanover', 'country': 'Germany', 'facility': '205.458.49001 Boehringer Ingelheim Investigational Site', 'geoPoint': {'lat': 52.37052, 'lon': 9.73322}}, {'city': 'Heerlen', 'country': 'Netherlands', 'facility': '205.458.31001 Atrium Medisch Centrum Parkstad', 'geoPoint': {'lat': 50.88365, 'lon': 5.98154}}, {'city': 'Winschoten', 'country': 'Netherlands', 'facility': '205.458.31002 Ommelander ziekenhuis groep, locatie Lucas', 'geoPoint': {'lat': 53.14417, 'lon': 7.03472}}], 'overallOfficials': [{'name': 'Boehringer Ingelheim', 'role': 'STUDY_CHAIR', 'affiliation': 'Boehringer Ingelheim'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Boehringer Ingelheim', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}