Ignite Creation Date:
2025-12-25 @ 12:43 AM
Ignite Modification Date:
2025-12-25 @ 10:55 PM
Study NCT ID:
NCT06180967
Status:
COMPLETED
Last Update Posted:
2025-02-24
First Post:
2023-12-13
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
A Drug Drug Interaction (DDI) Study of Pirtobrutinib (LOXO-305) and Different Formulations of Midazolam in Healthy Participants
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C000723100', 'term': 'pirtobrutinib'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'ClinicalTrials.gov@lilly.com', 'phone': '08005455979', 'title': 'Chief Medical Officer', 'organization': 'Eli Lilly and Company'}, 'certainAgreement': {'restrictionType': 'GT60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'From Day 1 up to 7 days post end of treatment (i.e., up to Day 30)', 'description': 'All participants who received at least 1 dose of study drugs (pirtobrutinib, IV midazolam, or oral midazolam). Participants were classified into groups based on actual treatment received.', 'eventGroups': [{'id': 'EG000', 'title': 'Period 1: IV Midazolam 250 mcg', 'description': 'Participants received a single IV bolus dose of midazolam 250 mcg solution on Day 1.', 'otherNumAtRisk': 15, 'deathsNumAtRisk': 15, 'otherNumAffected': 1, 'seriousNumAtRisk': 15, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Period 1: Oral Midazolam 500 mcg', 'description': 'Participants received a single oral dose of midazolam 500 mcg syrup on Day 3', 'otherNumAtRisk': 15, 'deathsNumAtRisk': 15, 'otherNumAffected': 0, 'seriousNumAtRisk': 15, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Period 2: Pirtobrutinib 200 mg', 'description': 'Participants received pirtobrutinib 200 mg tablets orally QD from Day 5 through Day 17.', 'otherNumAtRisk': 15, 'deathsNumAtRisk': 15, 'otherNumAffected': 3, 'seriousNumAtRisk': 15, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG003', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg', 'description': 'Participants received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.', 'otherNumAtRisk': 15, 'deathsNumAtRisk': 15, 'otherNumAffected': 1, 'seriousNumAtRisk': 15, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG004', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg', 'description': 'Participants received pirtobrutinib 200 mg tablets orally followed by oral dose of midazolam 500 mcg syrup on Day 17.', 'otherNumAtRisk': 15, 'deathsNumAtRisk': 15, 'otherNumAffected': 0, 'seriousNumAtRisk': 15, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Constipation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 15, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.0'}, {'term': 'Flatulence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 15, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.0'}, {'term': 'Injection site pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 15, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.0'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 15, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.0'}, {'term': 'Pollakiuria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 15, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.0'}, {'term': 'Nasal congestion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 15, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.0'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 15, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 15, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam) Following Oral Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: Oral Midazolam 500 mcg (Day 3)', 'description': 'Participants who received a single oral dose of midazolam 500 mcg syrup on Day 3.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by a single oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '4.81', 'spread': '40.8', 'groupId': 'OG000'}, {'value': '8.30', 'spread': '43.2', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-medazolam', 'categories': [{'measurements': [{'value': '2.24', 'spread': '41.9', 'groupId': 'OG000'}, {'value': '2.52', 'spread': '40.6', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: AUC0-t of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.', 'unitOfMeasure': 'Hours*nanograms per milliliter (h*ng/mL)', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of oral midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Area Under the Concentration-Time From Time 0 Extrapolated To Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: Oral Midazolam 500 mcg (Day 3)', 'description': 'Participants who received a single oral dose of midazolam 500 mcg syrup on Day 3.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by a single oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '5.31', 'spread': '43.1', 'groupId': 'OG000'}, {'value': '9.01', 'spread': '44.0', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-midazolam', 'categories': [{'measurements': [{'value': '2.60', 'spread': '39.9', 'groupId': 'OG000'}, {'value': '2.92', 'spread': '42.2', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: AUC(0-inf) of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.', 'unitOfMeasure': 'h*ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of oral midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: Oral Midazolam 500 mcg (Day 3)', 'description': 'Participants who received a single oral dose of midazolam 500 mcg syrup on Day 3.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by a single oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '8.84', 'spread': '33.7', 'groupId': 'OG000'}, {'value': '7.42', 'spread': '35.3', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-midazolam', 'categories': [{'measurements': [{'value': '12.9', 'spread': '37.5', 'groupId': 'OG000'}, {'value': '12.2', 'spread': '48.6', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: %AUCextrap of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.', 'unitOfMeasure': 'percentage of AUC0-inf', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of oral midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Maximum Observed Plasma Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: Oral Midazolam 500 mcg (Day 3)', 'description': 'Participants who received a single oral dose of midazolam 500 mcg syrup on Day 3.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by a single oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '2.33', 'spread': '36.7', 'groupId': 'OG000'}, {'value': '3.68', 'spread': '34.3', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-midazolam', 'categories': [{'measurements': [{'value': '1.25', 'spread': '42.2', 'groupId': 'OG000'}, {'value': '1.41', 'spread': '40.2', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: Cmax of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.', 'unitOfMeasure': 'nanograms per milliliter (ng/mL)', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of oral midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Time to Maximum Observed Plasma Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: Oral Midazolam 500 mcg (Day 3)', 'description': 'Participants who received a single oral dose of midazolam 500 mcg syrup on Day 3.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by a single oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '0.750', 'groupId': 'OG000', 'lowerLimit': '0.500', 'upperLimit': '1.00'}, {'value': '0.500', 'groupId': 'OG001', 'lowerLimit': '0.500', 'upperLimit': '0.750'}]}]}, {'title': 'Metabolite: 1-OH-midazolam', 'categories': [{'measurements': [{'value': '0.750', 'groupId': 'OG000', 'lowerLimit': '0.500', 'upperLimit': '1.00'}, {'value': '0.500', 'groupId': 'OG001', 'lowerLimit': '0.500', 'upperLimit': '1.00'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: tmax of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.', 'unitOfMeasure': 'Hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of oral midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Apparent Terminal Elimination Rate Constant (Lambda [λ] z) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: Oral Midazolam 500 mcg (Day 3)', 'description': 'Participants who received a single oral dose of midazolam 500 mcg syrup on Day 3.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by a single oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '0.316', 'spread': '50.7', 'groupId': 'OG000'}, {'value': '0.227', 'spread': '50.2', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-midazolam', 'categories': [{'measurements': [{'value': '0.441', 'spread': '35.4', 'groupId': 'OG000'}, {'value': '0.419', 'spread': '61.2', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: λz of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.', 'unitOfMeasure': 'one per hour (1/h)', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of oral midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Apparent Systemic Clearance (CL/F) of Midazolam Following Oral Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: Oral Midazolam 500 mcg (Day 3)', 'description': 'Participants who received a single oral dose of midazolam 500 mcg syrup on Day 3.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by a single oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'categories': [{'measurements': [{'value': '94.2', 'spread': '43.1', 'groupId': 'OG000'}, {'value': '55.5', 'spread': '44.0', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: CL/F of midazolam following oral dose administration was reported.', 'unitOfMeasure': 'Liters per hour (L/h)', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of oral midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Apparent Volume of Distribution (Vz/F) of Midazolam Following Oral Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: Oral Midazolam 500 mcg (Day 3)', 'description': 'Participants who received a single oral dose of midazolam 500 mcg syrup on Day 3.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by a single oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'categories': [{'measurements': [{'value': '298', 'spread': '29.7', 'groupId': 'OG000'}, {'value': '244', 'spread': '29.6', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: Vz/F of midazolam following oral dose administration was reported.', 'unitOfMeasure': 'Liters', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of oral midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Apparent Plasma Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: Oral Midazolam 500 mcg (Day 3)', 'description': 'Participants who received a single oral dose of midazolam 500 mcg syrup on Day 3.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by a single oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '2.20', 'spread': '50.7', 'groupId': 'OG000'}, {'value': '3.05', 'spread': '50.2', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-midazolam', 'categories': [{'measurements': [{'value': '1.57', 'spread': '35.4', 'groupId': 'OG000'}, {'value': '1.65', 'spread': '61.2', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: t½ of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.', 'unitOfMeasure': 'hours', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of oral midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Total Clearance (CL) of Midazolam Following Intravenous Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: IV Midazolam 250 mcg (Day 1)', 'description': 'Participants who received a single IV bolus dose of midazolam 250 mcg solution on Day 1.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}], 'classes': [{'categories': [{'measurements': [{'value': '26.0', 'spread': '21.4', 'groupId': 'OG000'}, {'value': '23.1', 'spread': '26.5', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: CL of midazolam following intravenous dose administration was reported.', 'unitOfMeasure': 'L/h', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of IV midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Volume of Distribution (Vz) of Midazolam Following Intravenous Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: IV Midazolam 250 mcg (Day 1)', 'description': 'Participants who received a single IV bolus dose of midazolam 250 mcg solution on Day 1.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}], 'classes': [{'categories': [{'measurements': [{'value': '113', 'spread': '34.2', 'groupId': 'OG000'}, {'value': '105', 'spread': '37.8', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: Vz of midazolam following intravenous dose administration was reported.', 'unitOfMeasure': 'Liters', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of IV midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Volume of Distribution at Steady State (Vss) of Midazolam Following Intravenous Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: IV Midazolam 250 mcg (Day 1)', 'description': 'Participants who received a single IV bolus dose of midazolam 250 mcg solution on Day 1.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}], 'classes': [{'categories': [{'measurements': [{'value': '78.2', 'spread': '29.4', 'groupId': 'OG000'}, {'value': '76.1', 'spread': '31.0', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: Vss of midazolam following intravenous dose administration was reported.', 'unitOfMeasure': 'Liters', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of IV midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: IV Midazolam 250 mcg (Day 1)', 'description': 'Participants who received a single IV bolus dose of midazolam 250 mcg solution on Day 1.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '8.89', 'spread': '21.6', 'groupId': 'OG000'}, {'value': '10.1', 'spread': '25.1', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-medazolam', 'categories': [{'measurements': [{'value': '1.39', 'spread': '41.7', 'groupId': 'OG000'}, {'value': '1.21', 'spread': '35.7', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: AUC0-t of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.', 'unitOfMeasure': 'h*ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of IV midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Area Under the Concentration-Time From Time 0 Extrapolated To Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: IV Midazolam 250 mcg (Day 1)', 'description': 'Participants who received a single IV bolus dose of midazolam 250 mcg solution on Day 1.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}], 'classes': [{'title': 'Midazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '9.62', 'spread': '21.4', 'groupId': 'OG000'}, {'value': '10.8', 'spread': '26.5', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-medazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '2.13', 'spread': '43.0', 'groupId': 'OG000'}, {'value': '1.62', 'spread': '25.2', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: AUC0-inf of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.', 'unitOfMeasure': 'h*ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': "All participants who received at least 1 dose of IV midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Here, 'Number analyzed' signifies participants with available data for each specified category."}, {'type': 'PRIMARY', 'title': 'PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: IV Midazolam 250 mcg (Day 1)', 'description': 'Participants who received a single IV bolus dose of midazolam 250 mcg solution on Day 1.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}], 'classes': [{'title': 'Midazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '7.13', 'spread': '37.1', 'groupId': 'OG000'}, {'value': '6.44', 'spread': '42.0', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-medazolam', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '19.6', 'spread': '24.7', 'groupId': 'OG000'}, {'value': '24.7', 'spread': '11.5', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: %AUCextrap of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.', 'unitOfMeasure': 'percentage of AUC0-inf', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': "All participants who received at least 1 dose of IV midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed. Here, 'Number analyzed' signifies participants with available data for each specified category."}, {'type': 'PRIMARY', 'title': 'PK: Maximum Observed Plasma Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: IV Midazolam 250 mcg (Day 1)', 'description': 'Participants who received a single IV bolus dose of midazolam 250 mcg solution on Day 1.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '6.96', 'spread': '34.8', 'groupId': 'OG000'}, {'value': '6.91', 'spread': '27.8', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-medazolam', 'categories': [{'measurements': [{'value': '0.512', 'spread': '31.7', 'groupId': 'OG000'}, {'value': '0.475', 'spread': '28.6', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: Cmax of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of IV midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Time to Maximum Observed Plasma Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: IV Midazolam 250 mcg (Day 1)', 'description': 'Participants who received a single IV bolus dose of midazolam 250 mcg solution on Day 1.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '0.0833', 'groupId': 'OG000', 'lowerLimit': '0.0833', 'upperLimit': '0.250'}, {'value': '0.0833', 'groupId': 'OG001', 'lowerLimit': '0.0833', 'upperLimit': '0.0833'}]}]}, {'title': 'Metabolite: 1-OH-medazolam', 'categories': [{'measurements': [{'value': '0.750', 'groupId': 'OG000', 'lowerLimit': '0.500', 'upperLimit': '1.00'}, {'value': '0.750', 'groupId': 'OG001', 'lowerLimit': '0.500', 'upperLimit': '1.00'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: tmax of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of IV midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Apparent Terminal Elimination Rate Constant (λz) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: IV Midazolam 250 mcg (Day 1)', 'description': 'Participants who received a single IV bolus dose of midazolam 250 mcg solution on Day 1.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '0.229', 'spread': '37.0', 'groupId': 'OG000'}, {'value': '0.221', 'spread': '49.5', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-medazolam', 'categories': [{'measurements': [{'value': '0.224', 'spread': '55.7', 'groupId': 'OG000'}, {'value': '0.282', 'spread': '47.8', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: λz of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.', 'unitOfMeasure': '1/h', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of IV midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'PRIMARY', 'title': 'PK: Apparent Plasma Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 1: IV Midazolam 250 mcg (Day 1)', 'description': 'Participants who received a single IV bolus dose of midazolam 250 mcg solution on Day 1.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}], 'classes': [{'title': 'Midazolam', 'categories': [{'measurements': [{'value': '3.02', 'spread': '37.0', 'groupId': 'OG000'}, {'value': '3.13', 'spread': '49.5', 'groupId': 'OG001'}]}]}, {'title': 'Metabolite: 1-OH-medazolam', 'categories': [{'measurements': [{'value': '3.09', 'spread': '55.7', 'groupId': 'OG000'}, {'value': '2.46', 'spread': '47.8', 'groupId': 'OG001'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: t1/2 of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.', 'unitOfMeasure': 'hours', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of IV midazolam had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'SECONDARY', 'title': 'PK: Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '15', 'groupId': 'OG002'}, {'value': '15', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 2: Pirtobrutinib 200 mg (Day 5)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally on Day 5.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg (Day 14)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally on Day 14.'}, {'id': 'OG002', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}, {'id': 'OG003', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'categories': [{'measurements': [{'value': '54800', 'spread': '20.0', 'groupId': 'OG000'}, {'value': '114000', 'spread': '26.0', 'groupId': 'OG001'}, {'value': '115000', 'spread': '25.0', 'groupId': 'OG002'}, {'value': '211000', 'spread': '33.8', 'groupId': 'OG003'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)', 'description': 'PK: AUC0-t of Pirtobrutinib was reported.', 'unitOfMeasure': 'h*ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK population included all participants who received at least 1 dose of pirtobrutinib had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'SECONDARY', 'title': 'PK: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '15', 'groupId': 'OG002'}, {'value': '15', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 2: Pirtobrutinib 200 mg (Day 5)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally on Day 5.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg (Day 14)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally on Day 14.'}, {'id': 'OG002', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}, {'id': 'OG003', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'categories': [{'measurements': [{'value': '55000', 'spread': '20.0', 'groupId': 'OG000'}, {'value': '114000', 'spread': '26.1', 'groupId': 'OG001'}, {'value': '116000', 'spread': '25.0', 'groupId': 'OG002'}, {'value': '118000', 'spread': '25.5', 'groupId': 'OG003'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)', 'description': 'PK: AUCtau of Pirtobrutinib was reported.', 'unitOfMeasure': 'h*ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK population included all participants who received at least 1 dose of pirtobrutinib had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'SECONDARY', 'title': 'PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '15', 'groupId': 'OG002'}, {'value': '15', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 2: Pirtobrutinib 200 mg (Day 5)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally on Day 5.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg (Day 14)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally on Day 14.'}, {'id': 'OG002', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}, {'id': 'OG003', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally in followed by oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'categories': [{'measurements': [{'value': '4880', 'spread': '18.5', 'groupId': 'OG000'}, {'value': '8120', 'spread': '27.1', 'groupId': 'OG001'}, {'value': '8620', 'spread': '23.1', 'groupId': 'OG002'}, {'value': '8750', 'spread': '27.2', 'groupId': 'OG003'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)', 'description': 'PK: Cmax of Pirtobrutinib was reported.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK population included all participants who received at least 1 dose of pirtobrutinib had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'SECONDARY', 'title': 'PK: Concentration Observed at the End Of the Dosing Interval (Ctrough) of Pirtobrutinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '15', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 2: Pirtobrutinib 200 mg (Day 14)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally on Day 14.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}, {'id': 'OG002', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'categories': [{'measurements': [{'value': '3060', 'spread': '32.1', 'groupId': 'OG000'}, {'value': '3180', 'spread': '36.4', 'groupId': 'OG001'}, {'value': '3050', 'spread': '32.7', 'groupId': 'OG002'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 2: 24-hour post-dose on Day 14, Day 15, and Day 17', 'description': 'PK: Ctrough of Pirtobrutinib before multiple oral doses administration was reported.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK population included all participants who received at least 1 dose of pirtobrutinib had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'SECONDARY', 'title': 'PK: Time To Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '15', 'groupId': 'OG002'}, {'value': '15', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 2: Pirtobrutinib 200 mg (Day 5)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally on Day 5.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg (Day 14)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally on Day 14.'}, {'id': 'OG002', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}, {'id': 'OG003', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'categories': [{'measurements': [{'value': '2.50', 'groupId': 'OG000', 'lowerLimit': '1.00', 'upperLimit': '4.00'}, {'value': '3.00', 'groupId': 'OG001', 'lowerLimit': '2.00', 'upperLimit': '4.00'}, {'value': '3.00', 'groupId': 'OG002', 'lowerLimit': '0.750', 'upperLimit': '6.00'}, {'value': '3.00', 'groupId': 'OG003', 'lowerLimit': '1.00', 'upperLimit': '4.00'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)', 'description': 'PK: tmax of Pirtobrutinib was reported.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK population included all participants who received at least 1 dose of pirtobrutinib had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'SECONDARY', 'title': 'PK: Apparent Systemic Plasma Clearance at Steady State (CL,ss/F) of Pirtobrutinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}, {'value': '15', 'groupId': 'OG001'}, {'value': '15', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 2: Pirtobrutinib 200 mg (Day 14)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally on Day 14.'}, {'id': 'OG001', 'title': 'Period 2: Pirtobrutinib 200 mg + IV Midazolam 250 mcg (Day 15)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by IV bolus dose of midazolam 250 mcg solution on Day 15.'}, {'id': 'OG002', 'title': 'Period 2: Pirtobrutinib 200 mg + Oral Midazolam 500 mcg (Day 17)', 'description': 'Participants who received pirtobrutinib 200 mg tablets orally followed by oral dose of midazolam 500 mcg syrup on Day 17.'}], 'classes': [{'categories': [{'measurements': [{'value': '1.75', 'spread': '26.1', 'groupId': 'OG000'}, {'value': '1.72', 'spread': '25.0', 'groupId': 'OG001'}, {'value': '1.69', 'spread': '25.5', 'groupId': 'OG002'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 2: Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)', 'description': 'PK: CL,ss/F of Pirtobrutinib was reported.', 'unitOfMeasure': 'L/h', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK population included all participants who received at least 1 dose of pirtobrutinib had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}, {'type': 'SECONDARY', 'title': 'PK: Accumulation Ratio (RAUC) of Pirtobrutinib', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Period 2: Pirtobrutinib 200 mg', 'description': 'Participants received Pirtobrutinib 200 mg tablets orally once daily (QD) in the morning from Day 5 through Day 17.'}], 'classes': [{'categories': [{'measurements': [{'value': '2.08', 'spread': '15.9', 'groupId': 'OG000'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Period 2: Day 5 and Day 14 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose)', 'description': 'RAUC was ratio of Day 14 AUCtau to Day 5 AUCtau.', 'unitOfMeasure': 'Ratio', 'dispersionType': 'Geometric Coefficient of Variation', 'reportingStatus': 'POSTED', 'populationDescription': 'The PK population included all participants who received at least 1 dose of pirtobrutinib had at least 1 quantifiable PK concentration, and for whom at least 1 PK parameter was computed.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Period 1: All Participants: Midazolam (IV + Oral Dose)', 'description': '* Day 1: Participants received a single intravenous (IV) bolus dose of midazolam 250 micrograms (mcg) solution on Day 1.\n* Day 3: Participants received a single oral dose of midazolam 500 mcg syrup on Day 3.\n\nA washout period of 2 days between midazolam IV dose and midazolam oral dose on Day 1 and Day 3 was observed.'}, {'id': 'FG001', 'title': 'Period 2: All Participants: Pirtobrutinib + Midazolam (IV + Oral Dose)', 'description': '* Day 5-17: Participants received Pirtobrutinib 200 mg tablets orally once daily (QD) in the morning from Day 5 through Day 17;\n* Day 15: Participants received single IV bolus dose of Midazolam 250 mcg followed by Pirtobrutinib intake on Day 15.\n* Day 17: Participants received a single oral dose of midazolam 500 mcg syrup followed by Pirtobrutinib intake on Day 17.\n\nA washout period of 2 days between midazolam IV dose and midazolam oral dose on Day 15 and Day 17 was observed.'}], 'periods': [{'title': 'Period 1: Day 1 to Day 4', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '15'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Received at Least 1 Dose of Study Drug', 'achievements': [{'groupId': 'FG000', 'numSubjects': '15'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '15'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Period 2: Day 5 to Day 20', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'comment': 'Participants who completed Period 1 continued to receive treatment in Period 2.', 'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'Received at Least 1 Dose of Study Drug', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '15'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': 'The study consisted of 2 periods: Period 1 and Period 2. A total of 15 healthy participants were enrolled in the study.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'All Participants: Midazolam (IV + Oral Dose) + Pirtobrutinib', 'description': 'All participants in the study who received:\n\n* Period 1, Day 1: Participants received a single intravenous (IV) bolus dose of midazolam 250 micrograms (mcg) solution on Day 1.\n* Period 1 Day 3: Participants received a single oral dose of midazolam 500 mcg syrup on Day 3. A washout period of 2 days between midazolam IV dose and midazolam oral dose on Day 1 and Day 3 was observed.\n* Period 2, Day 5-17: Participants received Pirtobrutinib 200 mg tablets orally once daily (QD) in the morning from Day 5 through Day 17\n* Period 2, Day 15: Participants received single IV bolus dose of Midazolam 250 mcg followed by Pirtobrutinib intake on Day 15.\n* Period 2, Day 17: Participants received a single oral dose of midazolam 500 mcg syrup followed by Pirtobrutinib intake on Day 17. A washout period of 2 days between midazolam IV dose and midazolam oral dose on Day 15 and Day 17 was observed.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '33.9', 'spread': '9.50', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '12', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'calculatePct': False, 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '7', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '8', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'calculatePct': False, 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'calculatePct': False, 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '15', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'calculatePct': False, 'unitOfMeasure': 'Participants'}], 'populationDescription': 'All participants who received at least 1 dose of study drug.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2020-09-13', 'size': 10301943, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2025-01-21T11:15', 'hasProtocol': True}, {'date': '2020-10-16', 'size': 28080382, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2025-01-21T11:18', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'SEQUENTIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 15}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-09-03', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2020-10-20', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-01-31', 'studyFirstSubmitDate': '2023-12-13', 'resultsFirstSubmitDate': '2025-01-31', 'studyFirstSubmitQcDate': '2023-12-13', 'lastUpdatePostDateStruct': {'date': '2025-02-24', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-01-31', 'studyFirstPostDateStruct': {'date': '2023-12-26', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2025-02-24', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-10-20', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam) Following Oral Dose Administration', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: AUC0-t of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.'}, {'measure': 'PK: Area Under the Concentration-Time From Time 0 Extrapolated To Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: AUC(0-inf) of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.'}, {'measure': 'PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: %AUCextrap of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.'}, {'measure': 'PK: Maximum Observed Plasma Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: Cmax of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.'}, {'measure': 'PK: Time to Maximum Observed Plasma Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: tmax of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.'}, {'measure': 'PK: Apparent Terminal Elimination Rate Constant (Lambda [λ] z) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: λz of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.'}, {'measure': 'PK: Apparent Systemic Clearance (CL/F) of Midazolam Following Oral Dose Administration', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: CL/F of midazolam following oral dose administration was reported.'}, {'measure': 'PK: Apparent Volume of Distribution (Vz/F) of Midazolam Following Oral Dose Administration', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: Vz/F of midazolam following oral dose administration was reported.'}, {'measure': 'PK: Apparent Plasma Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-Midazolam Following Oral Dose Administration', 'timeFrame': 'Period 1: Day 3 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: t½ of midazolam and its metabolite 1-OH-midazolam following oral dose administration was reported.'}, {'measure': 'PK: Total Clearance (CL) of Midazolam Following Intravenous Dose Administration', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: CL of midazolam following intravenous dose administration was reported.'}, {'measure': 'PK: Volume of Distribution (Vz) of Midazolam Following Intravenous Dose Administration', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: Vz of midazolam following intravenous dose administration was reported.'}, {'measure': 'PK: Volume of Distribution at Steady State (Vss) of Midazolam Following Intravenous Dose Administration', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: Vss of midazolam following intravenous dose administration was reported.'}, {'measure': 'PK: Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: AUC0-t of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.'}, {'measure': 'PK: Area Under the Concentration-Time From Time 0 Extrapolated To Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: AUC0-inf of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.'}, {'measure': 'PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: %AUCextrap of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.'}, {'measure': 'PK: Maximum Observed Plasma Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: Cmax of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.'}, {'measure': 'PK: Time to Maximum Observed Plasma Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: tmax of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.'}, {'measure': 'PK: Apparent Terminal Elimination Rate Constant (λz) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: λz of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.'}, {'measure': 'PK: Apparent Plasma Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam Following Intravenous Dose Administration', 'timeFrame': 'Period 1: Day 1 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose); Period 2: Day 15 (pre-dose, 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose)', 'description': 'PK: t1/2 of midazolam and its metabolite 1-OH-midazolam following intravenous dose administration was reported.'}], 'secondaryOutcomes': [{'measure': 'PK: Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib', 'timeFrame': 'Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)', 'description': 'PK: AUC0-t of Pirtobrutinib was reported.'}, {'measure': 'PK: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib', 'timeFrame': 'Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)', 'description': 'PK: AUCtau of Pirtobrutinib was reported.'}, {'measure': 'PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib', 'timeFrame': 'Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)', 'description': 'PK: Cmax of Pirtobrutinib was reported.'}, {'measure': 'PK: Concentration Observed at the End Of the Dosing Interval (Ctrough) of Pirtobrutinib', 'timeFrame': 'Period 2: 24-hour post-dose on Day 14, Day 15, and Day 17', 'description': 'PK: Ctrough of Pirtobrutinib before multiple oral doses administration was reported.'}, {'measure': 'PK: Time To Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib', 'timeFrame': 'Period 2: Day 5, Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)', 'description': 'PK: tmax of Pirtobrutinib was reported.'}, {'measure': 'PK: Apparent Systemic Plasma Clearance at Steady State (CL,ss/F) of Pirtobrutinib', 'timeFrame': 'Period 2: Day 14 and Day 15 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose), Day 17 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 100 hours post-dose)', 'description': 'PK: CL,ss/F of Pirtobrutinib was reported.'}, {'measure': 'PK: Accumulation Ratio (RAUC) of Pirtobrutinib', 'timeFrame': 'Period 2: Day 5 and Day 14 (pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours post-dose)', 'description': 'RAUC was ratio of Day 14 AUCtau to Day 5 AUCtau.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Healthy']}, 'descriptionModule': {'briefSummary': 'The main purpose of this study is to assess the effect of Pirtobrutinib (LOXO-305) on how fast different formulations of midazolam gets into the blood stream and how long it takes the body to remove it when administered in healthy participants. The study will also access how much endogenous coproporphyrins I and III as biomarkers of OATP1B1 and OATP1B3 is in the bloodstream and how the body handles and eliminates them following single and multiple oral doses of Pirtobrutinib. Safety and tolerability of Pirtobrutinib will also be evaluated. For each participant, the total duration of the study will be 59 days, including screening.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '55 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive\n* Male and female participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign measurements, or clinical laboratory evaluations as assessed by the investigator\n* Female participants of non-childbearing potential and male participants who follow standard contraceptive methods\n* Must have comply with all study procedures, including the 8-night stay at the Clinical Research Unit (CRU) and follow-up phone call\n\nExclusion Criteria:\n\n* History or presence of any diseases or conditions of clinical significance by the Investigator (or designee) and/or Sponsor\n* Positive serologic test for hepatitis B surface antigen (HBsAg), hepatitis B virus immunoglobulin M (HBV IgM) core antibody, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening\n* Positive polymerase chain reaction (PCR) test for COVID-19 at Screening or Check-in (Day -1)\n* Known ongoing alcohol and/or drug abuse within 2 years prior to Screening\n* History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee)\n* Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product'}, 'identificationModule': {'nctId': 'NCT06180967', 'briefTitle': 'A Drug Drug Interaction (DDI) Study of Pirtobrutinib (LOXO-305) and Different Formulations of Midazolam in Healthy Participants', 'organization': {'class': 'INDUSTRY', 'fullName': 'Eli Lilly and Company'}, 'officialTitle': 'A Phase I, Open Label, Fixed-sequence Drug Interaction Study to Investigate the Effect of Multiple Oral Doses of LOXO-305 on the Pharmacokinetics of a Single Dose of Intravenous and Oral Midazolam (CYP3A4 Substrate) in Healthy Subjects', 'orgStudyIdInfo': {'id': 'LOXO-BTK-20008'}, 'secondaryIdInfos': [{'id': 'J2N-OX-JZND', 'type': 'OTHER', 'domain': 'Eli Lilly and Company'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Midazolam (Intravenous [IV] Bolus)', 'description': 'A single IV bolus dose of midazolam will be administered in the morning following a 10-hour fast prior to dosing and a 4-hour fast postdose on Day 1 and Day 15.', 'interventionNames': ['Drug: Midazolam Solution']}, {'type': 'EXPERIMENTAL', 'label': 'Midazolam Oral', 'description': 'A single oral dose of midazolam will be administered in the morning following a 10-hour fast prior to dosing and a 4-hour fast postdose on Day 3 and Day 17.', 'interventionNames': ['Drug: Midazolam Syrup']}, {'type': 'EXPERIMENTAL', 'label': 'Pirtobrutinib', 'description': 'Multiple oral doses of Pirtobrutinib once a day (QD) will be administered on Days 5 through Day 17.', 'interventionNames': ['Drug: Pirtobrutinib']}], 'interventions': [{'name': 'Midazolam Syrup', 'type': 'DRUG', 'description': 'Administered Orally.', 'armGroupLabels': ['Midazolam Oral']}, {'name': 'Midazolam Solution', 'type': 'DRUG', 'description': 'Administered IV bolus.', 'armGroupLabels': ['Midazolam (Intravenous [IV] Bolus)']}, {'name': 'Pirtobrutinib', 'type': 'DRUG', 'otherNames': ['LOXO-305', 'LY3527727'], 'description': 'Administered Orally.', 'armGroupLabels': ['Pirtobrutinib']}]}, 'contactsLocationsModule': {'locations': [{'zip': '32117', 'city': 'Daytona Beach', 'state': 'Florida', 'country': 'United States', 'facility': 'Covance Clinical Research Unit', 'geoPoint': {'lat': 29.21081, 'lon': -81.02283}}], 'overallOfficials': [{'name': 'Renee Ward, MD, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Loxo Oncology, Inc.'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Eli Lilly and Company', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Loxo Oncology, Inc.', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}