Ignite Creation Date:
2025-12-25 @ 4:47 AM
Ignite Modification Date:
2025-12-26 @ 3:49 AM
Study NCT ID:
NCT01462318
Status:
COMPLETED
Last Update Posted:
2017-03-14
First Post:
2011-07-14
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
An Open-Label Immunogenicity and Pharmacokinetics Study of Daclizumab High Yield Process Prefilled Syringe in Relapsing Remitting Multiple Sclerosis
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['Russia']}, 'conditionBrowseModule': {'meshes': [{'id': 'D020529', 'term': 'Multiple Sclerosis, Relapsing-Remitting'}], 'ancestors': [{'id': 'D009103', 'term': 'Multiple Sclerosis'}, {'id': 'D020278', 'term': 'Demyelinating Autoimmune Diseases, CNS'}, {'id': 'D020274', 'term': 'Autoimmune Diseases of the Nervous System'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D003711', 'term': 'Demyelinating Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008874', 'term': 'Midazolam'}, {'id': 'D002110', 'term': 'Caffeine'}, {'id': 'D014859', 'term': 'Warfarin'}, {'id': 'D014812', 'term': 'Vitamin K'}, {'id': 'D009853', 'term': 'Omeprazole'}, {'id': 'D003915', 'term': 'Dextromethorphan'}, {'id': 'D000077561', 'term': 'Daclizumab'}, {'id': 'C000598527', 'term': 'daclizumab HYP'}], 'ancestors': [{'id': 'D001569', 'term': 'Benzodiazepines'}, {'id': 'D001552', 'term': 'Benzazepines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D014970', 'term': 'Xanthines'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D011688', 'term': 'Purinones'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D015110', 'term': '4-Hydroxycoumarins'}, {'id': 'D003374', 'term': 'Coumarins'}, {'id': 'D001578', 'term': 'Benzopyrans'}, {'id': 'D011714', 'term': 'Pyrans'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D009285', 'term': 'Naphthoquinones'}, {'id': 'D009281', 'term': 'Naphthalenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D010836', 'term': 'Phytol'}, {'id': 'D004224', 'term': 'Diterpenes'}, {'id': 'D013729', 'term': 'Terpenes'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D053799', 'term': '2-Pyridinylmethylsulfinylbenzimidazoles'}, {'id': 'D013454', 'term': 'Sulfoxides'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D011725', 'term': 'Pyridines'}, {'id': 'D001562', 'term': 'Benzimidazoles'}, {'id': 'D009019', 'term': 'Morphinans'}, {'id': 'D053610', 'term': 'Opiate Alkaloids'}, {'id': 'D006572', 'term': 'Heterocyclic Compounds, Bridged-Ring'}, {'id': 'D006576', 'term': 'Heterocyclic Compounds, 4 or More Rings'}, {'id': 'D010616', 'term': 'Phenanthrenes'}, {'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clinicaltrials@biogen.com', 'title': 'Biogen Study Medical Director', 'organization': 'Biogen'}, 'certainAgreement': {'otherDetails': "Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.", 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'From Screening (for serious adverse events) or first dose of study treatment on Day 1 (for adverse events) through the end of treatment', 'eventGroups': [{'id': 'EG000', 'title': 'DAC HYP 150 mg', 'description': "DAC HYP 150 mg by SC injection using the PFS every 4 weeks for24 weeks followed by a 20-week washout period. After completion of the washout period, participants could resume monthly DAC HYP 150 mg using the PFS for up to 3 additional years. Participants in the TP-DI sub-study received s probe-drug cocktail administration at Weeks 43 and 53. The probe-drug cocktail consisted of midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg. The oral vitamin K was used to counteract warfarin's anticoagulant effect prophylactically.", 'otherNumAtRisk': 133, 'otherNumAffected': 106, 'seriousNumAtRisk': 133, 'seriousNumAffected': 33}], 'otherEvents': [{'term': 'Lymphadenopathy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 8}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Hypothyroidism', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 7}], 'organSystem': 'Endocrine disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 9}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 12}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Influenza like illness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 13}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 12}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Influenza', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 8}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 19}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Oral herpes', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 7}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Pharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 15}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Sinusitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 11}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 33}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 30}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 9}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 10}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 14}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Muscle spasms', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 7}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Muscular weakness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 10}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 9}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Spinal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 7}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 21}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Hypoaesthesia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 9}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Migraine', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 7}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Multiple sclerosis relapse', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 58}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Muscle spasticity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 7}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Anxiety', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 11}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Depression', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 9}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 9}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}], 'seriousEvents': [{'term': 'Haemolytic anaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Lymphadenopathy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Neutropenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Autoimmune hepatitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Sarcoidosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Immune system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Furuncle', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Hepatitis E', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Pharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Streptococcal urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Toxicity to various agents', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Hepatic enzyme increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Obesity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Lumbar spinal stenosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Muscular weakness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Multiple sclerosis relapse', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 10}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Abortion missed', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Pregnancy, puerperium and perinatal conditions', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Depression', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Suicide attempt', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Hydronephrosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Endometrial hypertrophy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Endometriosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Ovarian cyst', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Postmenopausal haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 2}], 'organSystem': 'Reproductive system and breast disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Cutaneous sarcoidosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Erythema nodosum', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 133, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay', 'denoms': [{'units': 'Participants', 'counts': [{'value': '113', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Main Study', 'description': 'All participants received DAC HYP 150 mg SC injections every 4 weeks over an initial 24-week treatment period (for a total of 6 injections), followed by a 20-week washout period.\n\nThose participants from the Main Study who enrolled in the Intensive PK sub-study underwent serial DAC HYP PK sampling over the first and the last dosing intervals (on Day 1 \\[Week 0\\] and again on Day 141 \\[Week 20\\], the last dosing visit).'}], 'classes': [{'title': 'PB ADAbs through Week 44=negative; n=113', 'categories': [{'measurements': [{'value': '78', 'groupId': 'OG000'}]}]}, {'title': 'PB ADAbs through Week 44=positive; n=113', 'categories': [{'measurements': [{'value': '35', 'groupId': 'OG000'}]}]}, {'title': 'PB ADAbs in treatment period=negative; n=113', 'categories': [{'measurements': [{'value': '92', 'groupId': 'OG000'}]}]}, {'title': 'PB ADAbs in treatment period=positive; n=113', 'categories': [{'measurements': [{'value': '21', 'groupId': 'OG000'}]}]}, {'title': 'PB ADAbs in post-treatment period=negative; n=110', 'categories': [{'measurements': [{'value': '89', 'groupId': 'OG000'}]}]}, {'title': 'PB ADAbs in post-treatment period=positive; n=110', 'categories': [{'measurements': [{'value': '21', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Up to 44 weeks', 'description': 'Participants with post-baseline (PB) ADAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Immunogenicity evaluable population: all participants in the main study population who received at least 1 dose of DAC HYP and had at least 1 post-study baseline immunogenicity assessment; n=participants with an assessment during the given period.'}, {'type': 'PRIMARY', 'title': 'Number of Participants With Anti-DAC HYP Neutralizing Antibodies (NAbs): ECL ADA Assay', 'denoms': [{'units': 'Participants', 'counts': [{'value': '113', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Main Study', 'description': 'All participants received DAC HYP 150 mg SC injections every 4 weeks over an initial 24-week treatment period (for a total of 6 injections), followed by a 20-week washout period.\n\nThose participants from the Main Study who enrolled in the Intensive PK sub-study underwent serial DAC HYP PK sampling over the first and the last dosing intervals (on Day 1 \\[Week 0\\] and again on Day 141 \\[Week 20\\], the last dosing visit).'}], 'classes': [{'title': 'PB NAbs through Week 44=negative; n=113', 'categories': [{'measurements': [{'value': '105', 'groupId': 'OG000'}]}]}, {'title': 'PB NAbs through Week 44=positive; n=113', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000'}]}]}, {'title': 'PB NAbs in treatment period=negative; n=113', 'categories': [{'measurements': [{'value': '109', 'groupId': 'OG000'}]}]}, {'title': 'PB NAbs in treatment period=positive; n=113', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}]}]}, {'title': 'PB NAbs in post-treatment period=negative; n=110', 'categories': [{'measurements': [{'value': '104', 'groupId': 'OG000'}]}]}, {'title': 'PB NAbs in post-treatment period=positive; n=110', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Up to 44 weeks', 'description': 'Participants with PB NAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Immunogenicity evaluable population: all participants in the main study population who received at least 1 dose of DAC HYP and had at least 1 post-study baseline immunogenicity assessment; n=participants with an assessment during the given period.'}, {'type': 'PRIMARY', 'title': 'TP-DI Sub-study: Area-Under-the-Curve From Zero to Infinity (AUCinf) of Each Probe Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'TP-DI Sub-study', 'description': "In Period 1 (Week -1), the probe-drug cocktail (consisting of oral midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg, where the oral vitamin K was used prophylactically to counteract warfarin's anticoagulant effect) was administered 7 days before the first dose of DAC HYP 150 mg in the 3-year extension phase.\n\nIn Period 2, pretreatment with DAC HYP 150 mg was administered at Weeks 0, 4, and 8. The probe-drug cocktail was administered 7 days after the third dose of DAC HYP."}], 'classes': [{'title': 'Midazolam (Period 1) AUCinf; n=20', 'categories': [{'measurements': [{'value': '786.75', 'spread': '328.794', 'groupId': 'OG000'}]}]}, {'title': 'Midazolam+DAC HYP (Period 2) AUCinf; n=19', 'categories': [{'measurements': [{'value': '816.87', 'spread': '403.958', 'groupId': 'OG000'}]}]}, {'title': 'S-warfarin (Period 1) AUCinf; n=17', 'categories': [{'measurements': [{'value': '19292.9', 'spread': '5524.60', 'groupId': 'OG000'}]}]}, {'title': 'S-warfarin+DAC HYP (Period 2) AUCinf; n=18', 'categories': [{'measurements': [{'value': '19609.3', 'spread': '4620.64', 'groupId': 'OG000'}]}]}, {'title': 'Omeprazole (Period 1) AUCinf; n=18', 'categories': [{'measurements': [{'value': '2214.5', 'spread': '2622.15', 'groupId': 'OG000'}]}]}, {'title': 'Omeprazole+DAC HYP (Period 2) AUCinf; n=19', 'categories': [{'measurements': [{'value': '1770.0', 'spread': '1673.80', 'groupId': 'OG000'}]}]}, {'title': 'Caffeine (Period 1) AUC0-12; n=20', 'categories': [{'measurements': [{'value': '35742.4', 'spread': '13942.71', 'groupId': 'OG000'}]}]}, {'title': 'Caffeine+DAC HYP (Period 2) AUC0-12; n=20', 'categories': [{'measurements': [{'value': '37449.2', 'spread': '14367.04', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.015', 'ciLowerLimit': '0.894', 'ciUpperLimit': '1.153', 'estimateComment': 'test/reference = midazolam+DAC HYP/midazolam', 'groupDescription': 'Pairwise comparison: midazolam. Based on linear mixed model with fixed effect for treatment and random effect for participants.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'groupIds': ['OG000'], 'paramType': 'ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.005', 'ciLowerLimit': '0.951', 'ciUpperLimit': '1.063', 'estimateComment': 'test/reference = S-warfarin+DAC HYP/S-warfarin', 'groupDescription': 'Pairwise comparison: S-warfarin. Based on linear mixed model with fixed effect for treatment and random effect for participants.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'groupIds': ['OG000'], 'paramType': 'ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '0.996', 'ciLowerLimit': '0.880', 'ciUpperLimit': '1.127', 'estimateComment': 'test/reference = omeprazole+DAC HYP/omeprazole', 'groupDescription': 'Pairwise comparison: omeprazole. Based on linear mixed model with fixed effect for treatment and random effect for participants.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'groupIds': ['OG000'], 'paramType': 'ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.032', 'ciLowerLimit': '0.930', 'ciUpperLimit': '1.145', 'estimateComment': 'test/reference = caffeine+DAC HYP/caffeine', 'groupDescription': 'Pairwise comparison: caffeine. Based on linear mixed model with fixed effect for treatment and random effect for participants. Excludes participants with high predose concentration (\\>5% of maximum observed concentration \\[Cmax\\]).', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration', 'description': 'AUCinf of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), S-warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19). The AUC from zero to 12 hours (AUC0-12) was calculated for caffeine (CYP1A2).', 'unitOfMeasure': 'hr*ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'TP-DI Sub-study population: all participants in the TP-DI substudy who had enough post-baseline measurable drug concentrations to calculate the parameter; n=participants with an evaluable assessment at given time point.'}, {'type': 'PRIMARY', 'title': 'TP-DI Sub-study: Dextromethorphan to Dextrorphan Urine Concentration Ratio', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'TP-DI Sub-study', 'description': "In Period 1 (Week -1), the probe-drug cocktail (consisting of oral midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg, where the oral vitamin K was used prophylactically to counteract warfarin's anticoagulant effect) was administered 7 days before the first dose of DAC HYP 150 mg in the 3-year extension phase.\n\nIn Period 2, pretreatment with DAC HYP 150 mg was administered at Weeks 0, 4, and 8. The probe-drug cocktail was administered 7 days after the third dose of DAC HYP."}], 'classes': [{'title': 'Dextromethorphan (Period 1)', 'categories': [{'measurements': [{'value': '0.42468', 'spread': '1.258565', 'groupId': 'OG000'}]}]}, {'title': 'Dextromethorphan+DAC HYP (Period 2)', 'categories': [{'measurements': [{'value': '0.48939', 'spread': '1.813077', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.012', 'ciLowerLimit': '0.764', 'ciUpperLimit': '1.342', 'estimateComment': 'test/reference = dextromethorphan+DAC HYP/dextromethorphan', 'groupDescription': 'Pairwise comparison: dextromethorphan. Based on linear mixed model with fixed effect for treatment and random effect for participants.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and for 12 hours after probe-drug cocktail administration', 'unitOfMeasure': 'ratio', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'TP-DI Sub-study population: all participants in the TP-DI substudy who had enough post-baseline measurable drug concentrations to calculate the parameter; n=participants with an evaluable assessment at given time point.'}, {'type': 'SECONDARY', 'title': 'Intensive PK Sub-study: Cmax of DAC HYP', 'denoms': [{'units': 'Participants', 'counts': [{'value': '25', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Main Study', 'description': 'All participants received DAC HYP 150 mg SC injections every 4 weeks over an initial 24-week treatment period (for a total of 6 injections), followed by a 20-week washout period.\n\nThose participants from the Main Study who enrolled in the Intensive PK sub-study underwent serial DAC HYP PK sampling over the first and the last dosing intervals (on Day 1 \\[Week 0\\] and again on Day 141 \\[Week 20\\], the last dosing visit).'}], 'classes': [{'title': 'Day 1 (Week 0); n=25', 'categories': [{'measurements': [{'value': '12.63', 'spread': '4.639', 'groupId': 'OG000'}]}]}, {'title': 'Day 141 (Week 20); n=24', 'categories': [{'measurements': [{'value': '29.07', 'spread': '10.812', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14 and 21 days post-dose', 'unitOfMeasure': 'mcg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: all participants who participated in the Intensive PK sub-study and had enough post-study baseline measurable drug concentrations to calculate the parameter; n=participants with an assessment at given time point.'}, {'type': 'SECONDARY', 'title': 'Intensive PK Sub-study: Time to Reach Maximum Concentration (Tmax) of DAC HYP', 'denoms': [{'units': 'Participants', 'counts': [{'value': '25', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Main Study', 'description': 'All participants received DAC HYP 150 mg SC injections every 4 weeks over an initial 24-week treatment period (for a total of 6 injections), followed by a 20-week washout period.\n\nThose participants from the Main Study who enrolled in the Intensive PK sub-study underwent serial DAC HYP PK sampling over the first and the last dosing intervals (on Day 1 \\[Week 0\\] and again on Day 141 \\[Week 20\\], the last dosing visit).'}], 'classes': [{'title': 'Day 1 (Week 0); n=25', 'categories': [{'measurements': [{'value': '9.31', 'spread': '6.368', 'groupId': 'OG000'}]}]}, {'title': 'Day 141 (Week 20); n=24', 'categories': [{'measurements': [{'value': '6.41', 'spread': '3.273', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14 and 21 days post-dose', 'unitOfMeasure': 'day', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: all participants who participated in the Intensive PK sub-study and had enough post-study baseline measurable drug concentrations to calculate the parameter; n=participants with an assessment at given time point.'}, {'type': 'SECONDARY', 'title': 'Intensive PK Sub-study: Area-Under-the-Curve From Start to End of the Dosing Interval (AUCtau) of DAC HYP', 'denoms': [{'units': 'Participants', 'counts': [{'value': '25', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Main Study', 'description': 'All participants received DAC HYP 150 mg SC injections every 4 weeks over an initial 24-week treatment period (for a total of 6 injections), followed by a 20-week washout period.\n\nThose participants from the Main Study who enrolled in the Intensive PK sub-study underwent serial DAC HYP PK sampling over the first and the last dosing intervals (on Day 1 \\[Week 0\\] and again on Day 141 \\[Week 20\\], the last dosing visit).'}], 'classes': [{'title': 'Week 0 (Day 1); n=25', 'categories': [{'measurements': [{'value': '255.25', 'spread': '88.569', 'groupId': 'OG000'}]}]}, {'title': 'Week 20; n=24', 'categories': [{'measurements': [{'value': '638.10', 'spread': '256.076', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14, and 21 days post-dose', 'unitOfMeasure': 'day*mcg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: all participants who participated in the Intensive PK sub-study and had enough post-study baseline measurable drug concentrations to calculate the parameter; n=participants with an assessment at given time point.'}, {'type': 'SECONDARY', 'title': 'Intensive PK Sub-study: Minimum Concentrations (Cmin) of DAC HYP', 'denoms': [{'units': 'Participants', 'counts': [{'value': '24', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Main Study', 'description': 'All participants received DAC HYP 150 mg SC injections every 4 weeks over an initial 24-week treatment period (for a total of 6 injections), followed by a 20-week washout period.\n\nThose participants from the Main Study who enrolled in the Intensive PK sub-study underwent serial DAC HYP PK sampling over the first and the last dosing intervals (on Day 1 \\[Week 0\\] and again on Day 141 \\[Week 20\\], the last dosing visit).'}], 'classes': [{'categories': [{'measurements': [{'value': '14.93', 'spread': '6.327', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose', 'unitOfMeasure': 'mcg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: all participants who participated in the Intensive PK sub-study and had enough post-study baseline measurable drug concentrations to calculate the parameter.'}, {'type': 'SECONDARY', 'title': 'Intensive PK Sub-study: Apparent Volume of Distribution (V/F) of DAC HYP', 'denoms': [{'units': 'Participants', 'counts': [{'value': '24', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Main Study', 'description': 'All participants received DAC HYP 150 mg SC injections every 4 weeks over an initial 24-week treatment period (for a total of 6 injections), followed by a 20-week washout period.\n\nThose participants from the Main Study who enrolled in the Intensive PK sub-study underwent serial DAC HYP PK sampling over the first and the last dosing intervals (on Day 1 \\[Week 0\\] and again on Day 141 \\[Week 20\\], the last dosing visit).'}], 'classes': [{'categories': [{'measurements': [{'value': '8.21', 'spread': '2.810', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose', 'unitOfMeasure': 'Liters', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: all participants who participated in the Intensive PK sub-study and had enough post-study baseline measurable drug concentrations to calculate the parameter.'}, {'type': 'SECONDARY', 'title': 'Intensive PK Sub-study: Elimination Half-life (t½) of DAC HYP', 'denoms': [{'units': 'Participants', 'counts': [{'value': '24', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Main Study', 'description': 'All participants received DAC HYP 150 mg SC injections every 4 weeks over an initial 24-week treatment period (for a total of 6 injections), followed by a 20-week washout period.\n\nThose participants from the Main Study who enrolled in the Intensive PK sub-study underwent serial DAC HYP PK sampling over the first and the last dosing intervals (on Day 1 \\[Week 0\\] and again on Day 141 \\[Week 20\\], the last dosing visit).'}], 'classes': [{'categories': [{'measurements': [{'value': '21.92', 'spread': '5.473', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose', 'unitOfMeasure': 'day', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: all participants who participated in the Intensive PK sub-study and had enough post-study baseline measurable drug concentrations to calculate the parameter.'}, {'type': 'SECONDARY', 'title': 'Intensive PK Sub-study: Apparent Clearance (CL/F) of DAC HYP', 'denoms': [{'units': 'Participants', 'counts': [{'value': '24', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Main Study', 'description': 'All participants received DAC HYP 150 mg SC injections every 4 weeks over an initial 24-week treatment period (for a total of 6 injections), followed by a 20-week washout period.\n\nThose participants from the Main Study who enrolled in the Intensive PK sub-study underwent serial DAC HYP PK sampling over the first and the last dosing intervals (on Day 1 \\[Week 0\\] and again on Day 141 \\[Week 20\\], the last dosing visit).'}], 'classes': [{'categories': [{'measurements': [{'value': '0.27', 'spread': '0.108', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose', 'unitOfMeasure': 'L/day', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK population: all participants who participated in the Intensive PK sub-study and had enough post-study baseline measurable drug concentrations to calculate the parameter.'}, {'type': 'SECONDARY', 'title': 'TP-DI Sub-study: Cmax of Each Probe Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'TP-DI Sub-study', 'description': "In Period 1 (Week -1), the probe-drug cocktail (consisting of oral midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg, where the oral vitamin K was used prophylactically to counteract warfarin's anticoagulant effect) was administered 7 days before the first dose of DAC HYP 150 mg in the 3-year extension phase.\n\nIn Period 2, pretreatment with DAC HYP 150 mg was administered at Weeks 0, 4, and 8. The probe-drug cocktail was administered 7 days after the third dose of DAC HYP."}], 'classes': [{'title': 'Midazolam (Period 1); n=20', 'categories': [{'measurements': [{'value': '271.05', 'spread': '106.925', 'groupId': 'OG000'}]}]}, {'title': 'Midazolam+DAC HYP (Period 2); n=19', 'categories': [{'measurements': [{'value': '311.21', 'spread': '147.912', 'groupId': 'OG000'}]}]}, {'title': 'Caffeine (Period 1); n=20', 'categories': [{'measurements': [{'value': '4965.0', 'spread': '1312.69', 'groupId': 'OG000'}]}]}, {'title': 'Caffeine+DAC HYP (Period 2); n=19', 'categories': [{'measurements': [{'value': '5399.5', 'spread': '1364.05', 'groupId': 'OG000'}]}]}, {'title': 'S-Warfarin (Period 1); n=20', 'categories': [{'measurements': [{'value': '635.65', 'spread': '140.291', 'groupId': 'OG000'}]}]}, {'title': 'S-Warfarin+DAC HYP (Period 2); n=19', 'categories': [{'measurements': [{'value': '649.74', 'spread': '155.977', 'groupId': 'OG000'}]}]}, {'title': 'Omeprazole (Period 1); n=19', 'categories': [{'measurements': [{'value': '776.95', 'spread': '513.344', 'groupId': 'OG000'}]}]}, {'title': 'Omeprazole+DAC HYP (Period 2); n=19', 'categories': [{'measurements': [{'value': '771.16', 'spread': '540.331', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.079', 'ciLowerLimit': '0.912', 'ciUpperLimit': '1.276', 'estimateComment': 'test/reference = midazolam+DAC HYP/midazolam', 'groupDescription': 'Pairwise comparison: midazolam. Based on linear mixed model with fixed effect for treatment and random effect for participants.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'groupIds': ['OG000'], 'paramType': 'ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.012', 'ciLowerLimit': '0.952', 'ciUpperLimit': '1.075', 'estimateComment': 'test/reference = S-warfarin+DAC HYP/S-warfarin', 'groupDescription': 'Pairwise comparison: S-warfarin. Based on linear mixed model with fixed effect for treatment and random effect for participants.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'groupIds': ['OG000'], 'paramType': 'ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.058', 'ciLowerLimit': '0.804', 'ciUpperLimit': '1.392', 'estimateComment': 'test/reference = omeprazole+DAC HYP/omeprazole', 'groupDescription': 'Pairwise comparison: omeprazole. Based on linear mixed model with fixed effect for treatment and random effect for participants.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}, {'groupIds': ['OG000'], 'paramType': 'ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.116', 'ciLowerLimit': '1.005', 'ciUpperLimit': '1.238', 'estimateComment': 'test/reference = caffeine+DAC HYP/caffeine', 'groupDescription': 'Pairwise comparison: caffeine. Based on linear mixed model with fixed effect for treatment and random effect for participants. Excludes participants with high predose concentration (\\>5% of Cmax).', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration', 'description': 'Cmax of each of the following CYP isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19).', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'TP-DI Substudy population: all participants in the TP-DI substudy who had enough post-baseline measurable drug concentrations to calculate the parameter; n=participants with an evaluable assessment at given time point.'}, {'type': 'SECONDARY', 'title': 'TP-DI Sub-study: CL/F of Each Probe Drug', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'TP-DI Sub-study', 'description': "In Period 1 (Week -1), the probe-drug cocktail (consisting of oral midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg, where the oral vitamin K was used prophylactically to counteract warfarin's anticoagulant effect) was administered 7 days before the first dose of DAC HYP 150 mg in the 3-year extension phase.\n\nIn Period 2, pretreatment with DAC HYP 150 mg was administered at Weeks 0, 4, and 8. The probe-drug cocktail was administered 7 days after the third dose of DAC HYP."}], 'classes': [{'title': 'Midazolam (Period 1); n=20', 'categories': [{'measurements': [{'value': '7625.7', 'spread': '3849.92', 'groupId': 'OG000'}]}]}, {'title': 'Midazolam+DAC HYP (Period 2); n=19', 'categories': [{'measurements': [{'value': '7298.6', 'spread': '2844.22', 'groupId': 'OG000'}]}]}, {'title': 'S-Warfarin (Period 1); n=17', 'categories': [{'measurements': [{'value': '565.86', 'spread': '184.129', 'groupId': 'OG000'}]}]}, {'title': 'S-Warfarin+DAC HYP (Period 2); n=18', 'categories': [{'measurements': [{'value': '541.46', 'spread': '150.298', 'groupId': 'OG000'}]}]}, {'title': 'Omeprazole (Period 1); n=18', 'categories': [{'measurements': [{'value': '41612.4', 'spread': '30003.48', 'groupId': 'OG000'}]}]}, {'title': 'Omeprazole+DAC HYP (Period 2); n=19', 'categories': [{'measurements': [{'value': '41772.4', 'spread': '29810.30', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration', 'description': 'CL/F of each of the following CYP isoenzyme substrates: midazolam (CYP3A), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19).', 'unitOfMeasure': 'mL/hr', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'TP-DI Sub-study population: all participants in the TP-DI substudy who had enough post-baseline measurable drug concentrations to calculate the parameter; n=participants with an evaluable assessment at given time point.'}, {'type': 'SECONDARY', 'title': 'TP-DI Sub-study: Omeprazole/Hydroxyomeprazole Concentration Ratio at 2 Hours Post-omeprazole Dosing', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'TP-DI Sub-study', 'description': "In Period 1 (Week -1), the probe-drug cocktail (consisting of oral midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg, where the oral vitamin K was used prophylactically to counteract warfarin's anticoagulant effect) was administered 7 days before the first dose of DAC HYP 150 mg in the 3-year extension phase.\n\nIn Period 2, pretreatment with DAC HYP 150 mg was administered at Weeks 0, 4, and 8. The probe-drug cocktail was administered 7 days after the third dose of DAC HYP."}], 'classes': [{'title': 'Omeprazole (Period 1)', 'categories': [{'measurements': [{'value': '2.673', 'spread': '4.7878', 'groupId': 'OG000'}]}]}, {'title': 'Omeprazole+ DAC HYP (Period 2)', 'categories': [{'measurements': [{'value': '1.028', 'spread': '0.9297', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '0.878', 'ciLowerLimit': '0.697', 'ciUpperLimit': '1.105', 'estimateComment': 'test/reference = omeprazole+DAC HYP/omeprazole', 'groupDescription': 'Pairwise comparison: omeprazole. Based on linear mixed model with fixed effect for treatment and random effect for participants.', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration) at 2 hours after probe drug cocktail administration', 'unitOfMeasure': 'ratio', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'TP-DI Sub-study population: all participants in the TP-DI substudy who had enough post-baseline measurable drug concentrations to calculate the parameter.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Main Study', 'description': 'All participants received DAC HYP 150 mg SC injections every 4 weeks over an initial 24-week treatment period (for a total of 6 injections), followed by a 20-week washout period.\n\nThose participants from the Main Study who enrolled in the Intensive PK sub-study underwent serial DAC HYP PK sampling over the first and the last dosing intervals (on Day 1 \\[Week 0\\] and again on Day 141 \\[Week 20\\], the last dosing visit).'}, {'id': 'FG001', 'title': 'Therapeutic Protein-Drug Interaction (TP-DI)Sub-study', 'description': "In Period 1 (Week -1), the probe-drug cocktail (consisting of oral midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg, where the oral vitamin K was used prophylactically to counteract warfarin's anticoagulant effect) was administered 7 days before the first dose of DAC HYP 150 mg in the 3-year extension phase.\n\nIn Period 2, pretreatment with DAC HYP 150 mg was administered at Weeks 0, 4, and 8. The probe-drug cocktail was administered 7 days after the third dose of DAC HYP."}, {'id': 'FG002', 'title': 'Extension Phase', 'description': 'After completion of the washout period from the Main Study or the TP-DI sub-study, eligible participants had the option to resume monthly open-label treatment with DAC HYP 150 mg in the extension phase of the study for up to 3 additional years.'}], 'periods': [{'title': 'Main Study / TP-DI Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '113'}, {'groupId': 'FG001', 'numSubjects': '20'}, {'groupId': 'FG002', 'numSubjects': '0'}]}, {'type': 'Enrolled in Intensive PK Substudy', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '105'}, {'groupId': 'FG001', 'numSubjects': '20'}, {'groupId': 'FG002', 'numSubjects': '0'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Other', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}]}, {'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}]}]}, {'title': 'Extension Phase', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': '95 participants from the Main Study entered the Extension Phase', 'groupId': 'FG000', 'numSubjects': '0'}, {'comment': '20 participants from the TP-DI Study entered the Extension Phase', 'groupId': 'FG001', 'numSubjects': '0'}, {'comment': '10 participants from the Main Study did not enter the Extension Phase.', 'groupId': 'FG002', 'numSubjects': '115'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '70'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '45'}]}], 'dropWithdraws': [{'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}]}, {'type': 'Other', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}]}, {'type': 'Disease Progression', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '1'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '15'}]}, {'type': 'Investigator Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '5'}]}, {'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '22'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '113', 'groupId': 'BG000'}, {'value': '20', 'groupId': 'BG001'}, {'value': '133', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Main Study', 'description': 'All participants received DAC HYP 150 mg SC injections every 4 weeks over an initial 24-week treatment period (for a total of 6 injections), followed by a 20-week washout period.\n\nThose participants from the Main Study who enrolled in the Intensive PK sub-study underwent serial DAC HYP PK sampling over the first and the last dosing intervals (on Day 1 \\[Week 0\\] and again on Day 141 \\[Week 20\\], the last dosing visit).'}, {'id': 'BG001', 'title': 'TP-DI Sub-study', 'description': "In Period 1 (Week -1), the probe-drug cocktail (consisting of oral midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg, where the oral vitamin K was used prophylactically to counteract warfarin's anticoagulant effect) was administered 7 days before the first dose of DAC HYP 150 mg in the 3-year extension phase.\n\nIn Period 2, pretreatment with DAC HYP 150 mg was administered at Weeks 0, 4, and 8. The probe-drug cocktail was administered 7 days after the third dose of DAC HYP."}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Customized', 'classes': [{'title': '< 18 years', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}, {'title': '18 - 19 years', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}, {'title': '20 - 29 years', 'categories': [{'measurements': [{'value': '28', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '32', 'groupId': 'BG002'}]}]}, {'title': '30 - 39 years', 'categories': [{'measurements': [{'value': '40', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '47', 'groupId': 'BG002'}]}]}, {'title': '40 - 49 years', 'categories': [{'measurements': [{'value': '31', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '36', 'groupId': 'BG002'}]}]}, {'title': '50 - 55 years', 'categories': [{'measurements': [{'value': '14', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '17', 'groupId': 'BG002'}]}]}, {'title': '> 55 years', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '72', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '85', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '41', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '48', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 133}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-01', 'dispFirstSubmitDate': '2014-10-13', 'completionDateStruct': {'date': '2016-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-01-23', 'studyFirstSubmitDate': '2011-07-14', 'dispFirstSubmitQcDate': '2014-10-13', 'resultsFirstSubmitDate': '2017-01-23', 'studyFirstSubmitQcDate': '2011-10-28', 'dispFirstPostDateStruct': {'date': '2014-10-22', 'type': 'ESTIMATED'}, 'lastUpdatePostDateStruct': {'date': '2017-03-14', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-01-23', 'studyFirstPostDateStruct': {'date': '2011-10-31', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-03-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay', 'timeFrame': 'Up to 44 weeks', 'description': 'Participants with post-baseline (PB) ADAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).'}, {'measure': 'Number of Participants With Anti-DAC HYP Neutralizing Antibodies (NAbs): ECL ADA Assay', 'timeFrame': 'Up to 44 weeks', 'description': 'Participants with PB NAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose).'}, {'measure': 'TP-DI Sub-study: Area-Under-the-Curve From Zero to Infinity (AUCinf) of Each Probe Drug', 'timeFrame': 'Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration', 'description': 'AUCinf of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), S-warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19). The AUC from zero to 12 hours (AUC0-12) was calculated for caffeine (CYP1A2).'}, {'measure': 'TP-DI Sub-study: Dextromethorphan to Dextrorphan Urine Concentration Ratio', 'timeFrame': 'Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and for 12 hours after probe-drug cocktail administration'}], 'secondaryOutcomes': [{'measure': 'Intensive PK Sub-study: Cmax of DAC HYP', 'timeFrame': 'Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14 and 21 days post-dose'}, {'measure': 'Intensive PK Sub-study: Time to Reach Maximum Concentration (Tmax) of DAC HYP', 'timeFrame': 'Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14 and 21 days post-dose'}, {'measure': 'Intensive PK Sub-study: Area-Under-the-Curve From Start to End of the Dosing Interval (AUCtau) of DAC HYP', 'timeFrame': 'Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14, and 21 days post-dose'}, {'measure': 'Intensive PK Sub-study: Minimum Concentrations (Cmin) of DAC HYP', 'timeFrame': 'Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose'}, {'measure': 'Intensive PK Sub-study: Apparent Volume of Distribution (V/F) of DAC HYP', 'timeFrame': 'Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose'}, {'measure': 'Intensive PK Sub-study: Elimination Half-life (t½) of DAC HYP', 'timeFrame': 'Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose'}, {'measure': 'Intensive PK Sub-study: Apparent Clearance (CL/F) of DAC HYP', 'timeFrame': 'Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose'}, {'measure': 'TP-DI Sub-study: Cmax of Each Probe Drug', 'timeFrame': 'Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration', 'description': 'Cmax of each of the following CYP isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19).'}, {'measure': 'TP-DI Sub-study: CL/F of Each Probe Drug', 'timeFrame': 'Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration', 'description': 'CL/F of each of the following CYP isoenzyme substrates: midazolam (CYP3A), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19).'}, {'measure': 'TP-DI Sub-study: Omeprazole/Hydroxyomeprazole Concentration Ratio at 2 Hours Post-omeprazole Dosing', 'timeFrame': 'Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration) at 2 hours after probe drug cocktail administration'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Pre-filled syringe', 'Pharmacokinetic', 'Daclizumab High Yield Process', 'immunogenicity'], 'conditions': ['Relapsing-Remitting Multiple Sclerosis']}, 'referencesModule': {'references': [{'pmid': '27411694', 'type': 'DERIVED', 'citation': 'Gold R, Stefoski D, Selmaj K, Havrdova E, Hurst C, Holman J, Tornesi B, Akella S, McCroskery P. Pregnancy Experience: Nonclinical Studies and Pregnancy Outcomes in the Daclizumab Clinical Study Program. Neurol Ther. 2016 Dec;5(2):169-182. doi: 10.1007/s40120-016-0048-2. Epub 2016 Jul 13.'}]}, 'descriptionModule': {'briefSummary': 'The primary objective of the study is to assess the immunogenicity of Daclizumab High Yield Process (DAC HYP) 150 mg administered every 4 weeks by subcutaneous (SC) injection using the pre-filled syringe (PFS) in participants with relapsing-remitting multiple sclerosis (RRMS). The secondary objectives of this study are to characterize the pharmacokinetics (PK) of DAC HYP following single and multiple doses of DAC HYP administered by the PFS in a subset of participants with RRMS and to evaluate the effect of DAC HYP on the PK of probe drugs for cytochrome P450 (CYP) isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A).', 'detailedDescription': 'Following a screening period, participants will receive DAC HYP over a 24-week treatment period (6 monthly injections) and then enter a 20-week washout period for assessment of immunogenicity, PK, pharmacodynamics, safety, and tolerability. The 20-week washout is necessary to ensure measurement of anti-DAC HYP binding antibodies (ADAbs) and neutralizing antibodies (NAbs) in the absence of drug interference. After washout, the participants may resume monthly treatment with DAC HYP 150 mg for an additional 3 years. All participants will be followed for 6 months after their last dose for safety monitoring. Additionally, two sub-studies will be performed: (1) an intensive serial PK sampling performed over the first and last dosing interval following DAC HYP doses administered at week 0 and at week 20, and (2) a therapeutic protein-drug interaction (TP-DI) sub-study, during which a probe drug cocktail will be administered at weeks 43 and 53 followed by serial probe-drug PK sampling up to 96 hours after probe-drug administration. A maximum of 20 participants will be enrolled in the TP-DI sub-study.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Key Inclusion Criteria:\n\n* Must have a confirmed diagnosis of RRMS according to McDonald criteria and previous cranial magnetic resonance imaging demonstrating lesion(s) consistent with MS\n* Must have a baseline Expanded Disability Status Scale (EDSS) between 0.0 and 5.0, inclusive\n* Must have had 1 or more clinical relapses within the previous 2 years\n* Women of child bearing potential must be willing to practice effective contraception during the study and 4 months after the last dose\n\nKey Exclusion Criteria:\n\n* Other chronic disease of the immune system, malignancies, acute urologic, pulmonary, gastrointestinal disease\n* Female subjects who are currently pregnant or breastfeeding\n\nKey Inclusion criteria for 3-Year Treatment Extension:\n\nTo be eligible for participation in the 3-year treatment extension, participants must meet the following eligibility criteria at the time of reinitiation of DAC HYP:\n\n* Must have been compliant with the 205MS302 (NCT01462318) protocol during the initial 24-week treatment period and the 20-week washout period in the opinion of the Investigator\n* Must resume DAC HYP treatment ≤12 weeks after completion of the washout period (i.e., ≤12 weeks after their Week 44 visit).\n* Participants who are currently receiving an approved IFN ß preparation must discontinue interferon (IFN) ß treatment at the time of reinitiation of DAC HYP dosing (no washout is required).\n\nKey Inclusion criteria for the TP-DI Sub-study:\n\nTo be eligible for participation in the TP-DI Sub-Study, subjects must meet the following eligibility criteria at the Screening Visit at Week 40:\n\n* Must have been compliant with the 205MS302 (NCT01462318) protocol during the initial 24-week treatment period and through Week 40 of the 20-week washout period in the opinion of the Investigator.\n* Must agree to resume DAC HYP treatment ≤12 weeks after completion of the washout period (i.e., ≤12 weeks after their Week 44 visit).\n* Must have normal liver function test results (total bilirubin ≤1.5 × upper limit of normal (ULN), alanine aminotransferase/aspartate aminotransferase ≤2 × ULN, and prothrombin time/partial thromboplastin time ≤1.2 × ULN).\n* Must have normal renal function as estimated creatinine clearance \\>60 mL/min (Cockcroft-Gault formula).\n\nNOTE: Other protocol defined Inclusion/Exclusion criteria may apply.'}, 'identificationModule': {'nctId': 'NCT01462318', 'acronym': 'OBSERVE', 'briefTitle': 'An Open-Label Immunogenicity and Pharmacokinetics Study of Daclizumab High Yield Process Prefilled Syringe in Relapsing Remitting Multiple Sclerosis', 'organization': {'class': 'INDUSTRY', 'fullName': 'Biogen'}, 'officialTitle': 'A Multicenter, Single-Arm, Open-Label Study to Evaluate the Immunogenicity and Pharmacokinetics of BIIB019, Daclizumab High Yield Process (DAC HYP), Prefilled Syringe Administered by Subcutaneous Injection in Subjects With Relapsing-Remitting Multiple Sclerosis', 'orgStudyIdInfo': {'id': '205MS302'}, 'secondaryIdInfos': [{'id': '2010-023856-97', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'DAC HYP', 'description': "DAC HYP 150 mg by a subcutaneous (SC) injection using the pre-filled syringe (PFS) every 4 weeks for 24 weeks followed by a 20-week washout period. After completion of the washout period, participants may resume monthly DAC HYP 150 mg using the PFS for up to 3 additional years.\n\nParticipants in the TP-DI sub-study will receive probe-drug cocktail administration at Weeks 43 and 53. The probe-drug cocktail consists of oral midazolam 5 mg, caffeine 200 mg, S-warfarin 10 mg, vitamin K 10 mg, omeprazole 40 mg, and dextromethorphan 30 mg. The oral vitamin K is used to counteract warfarin's anticoagula nt effect prophylactically.", 'interventionNames': ['Drug: Midazolam', 'Other: Caffeine', 'Drug: S-warfarin', 'Other: Vitamin K', 'Drug: Omeprazole', 'Drug: Dextromethorphan', 'Biological: BIIB019 (Daclizumab)']}], 'interventions': [{'name': 'Midazolam', 'type': 'DRUG', 'description': '5 mg', 'armGroupLabels': ['DAC HYP']}, {'name': 'Caffeine', 'type': 'OTHER', 'description': '200 mg', 'armGroupLabels': ['DAC HYP']}, {'name': 'S-warfarin', 'type': 'DRUG', 'description': '10 mg', 'armGroupLabels': ['DAC HYP']}, {'name': 'Vitamin K', 'type': 'OTHER', 'description': '10 mg', 'armGroupLabels': ['DAC HYP']}, {'name': 'Omeprazole', 'type': 'DRUG', 'description': '40 mg', 'armGroupLabels': ['DAC HYP']}, {'name': 'Dextromethorphan', 'type': 'DRUG', 'description': '30 mg', 'armGroupLabels': ['DAC HYP']}, {'name': 'BIIB019 (Daclizumab)', 'type': 'BIOLOGICAL', 'otherNames': ['Daclizumab High Yield Process; DAC HYP'], 'description': '150 mg in 1 ml PFS', 'armGroupLabels': ['DAC HYP']}]}, 'contactsLocationsModule': {'locations': [{'zip': '80112', 'city': 'Centennial', 'state': 'Colorado', 'country': 'United States', 'facility': 'Research Site', 'geoPoint': {'lat': 39.57916, 'lon': -104.87692}}, {'zip': '20057', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': 'Research Site', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '60010', 'city': 'Lake Barrington', 'state': 'Illinois', 'country': 'United States', 'facility': 'Research Site', 'geoPoint': {'lat': 42.21252, 'lon': -88.15258}}, {'zip': '40513', 'city': 'Lexington', 'state': 'Kentucky', 'country': 'United States', 'facility': 'Research Site', 'geoPoint': {'lat': 37.98869, 'lon': -84.47772}}, {'zip': '48334', 'city': 'Farmington Hills', 'state': 'Michigan', 'country': 'United States', 'facility': 'Research Site', 'geoPoint': {'lat': 42.48531, 'lon': -83.37716}}, {'zip': '45417', 'city': 'Dayton', 'state': 'Ohio', 'country': 'United States', 'facility': 'Research Site', 'geoPoint': {'lat': 39.75895, 'lon': -84.19161}}, {'zip': '37064', 'city': 'Franklin', 'state': 'Tennessee', 'country': 'United States', 'facility': 'Research Site', 'geoPoint': {'lat': 35.92506, 'lon': -86.86889}}, {'zip': '65691', 'city': 'Brno', 'country': 'Czechia', 'facility': 'Research Site', 'geoPoint': {'lat': 49.19522, 'lon': 16.60796}}, {'zip': '58633', 'city': 'Jihlava', 'country': 'Czechia', 'facility': 'Research Site', 'geoPoint': {'lat': 49.3961, 'lon': 15.59124}}, {'zip': '70852', 'city': 'Ostrava', 'country': 'Czechia', 'facility': 'Research Site', 'geoPoint': {'lat': 49.83465, 'lon': 18.28204}}, {'zip': '53203', 'city': 'Pardubice', 'country': 'Czechia', 'facility': 'Research Site', 'geoPoint': {'lat': 50.04075, 'lon': 15.77659}}, {'zip': '41501', 'city': 'Teplice', 'country': 'Czechia', 'facility': 'Research Site', 'geoPoint': {'lat': 50.6404, 'lon': 13.82451}}, {'zip': '8200', 'city': 'Veszprém', 'state': 'Korhazu 1', 'country': 'Hungary', 'facility': 'Research Site', 'geoPoint': {'lat': 47.09327, 'lon': 17.91149}}, {'zip': '1134', 'city': 'Budapest', 'country': 'Hungary', 'facility': 'Research Site', 'geoPoint': {'lat': 47.49835, 'lon': 19.04045}}, {'zip': '4031', 'city': 'Debrecen', 'country': 'Hungary', 'facility': 'Research Site', 'geoPoint': {'lat': 47.53167, 'lon': 21.62444}}, {'zip': '2500', 'city': 'Esztergom', 'country': 'Hungary', 'facility': 'Research Site', 'geoPoint': {'lat': 47.7928, 'lon': 18.74148}}, {'city': 'Székesfehérvár', 'country': 'Hungary', 'facility': 'Research Site', 'geoPoint': {'lat': 47.18995, 'lon': 18.41034}}, {'city': 'Katowice', 'country': 'Poland', 'facility': 'Research Site', 'geoPoint': {'lat': 50.2597, 'lon': 19.02173}}, {'zip': '31-501', 'city': 'Krakow', 'country': 'Poland', 'facility': 'Research Site', 'geoPoint': {'lat': 50.06143, 'lon': 19.93658}}], 'overallOfficials': [{'name': 'Medical Director', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Biogen'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Biogen', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}