Ignite Creation Date:
2025-12-24 @ 3:07 PM
Ignite Modification Date:
2026-01-22 @ 5:32 AM
Study NCT ID:
NCT02254759
Status:
COMPLETED
Last Update Posted:
2016-11-02
First Post:
2014-09-23
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study of RO5186582 Treatment on Cytochrome P450 (CYP) 3A4 Activity in Healthy Participants
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D008874', 'term': 'Midazolam'}], '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'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 12}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-11', 'completionDateStruct': {'date': '2014-11', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-11-01', 'studyFirstSubmitDate': '2014-09-23', 'studyFirstSubmitQcDate': '2014-09-29', 'lastUpdatePostDateStruct': {'date': '2016-11-02', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2014-10-02', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Bioavailability of Drug (F) for Oral Midazolam', 'timeFrame': 'Pre-dose [-0.5 hour (h)] and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 14 h post-dose (pd) on Day (D) 2 and 18, and 22 h pd on D3 and 19'}, {'measure': 'Total Plasma Clearence (CL) for IV Midazolam', 'timeFrame': 'Pre-dose [-10 minutes (min)] and 0.08 (5 min), 0.25 (15 min), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 14 h pd on D1 and D17, and 22 h pd on D2 and D18'}, {'measure': 'Apparent Volume of Distribution at Steady-State (Vss) for IV Midazolam', 'timeFrame': 'Pre-dose (-10 min) and 0.08 (5 min), 0.25 (15 min), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 14 h pd on D1 and D17, and 22 h pd on D2 and D18'}, {'measure': 'Maximum Observed Plasma Concentration (Cmax) for Oral Midazolam', 'timeFrame': 'Pre-dose (-0.5 h) and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 14 h pd on D2 and 18, and 22 h pd on D3 and D19'}], 'secondaryOutcomes': [{'measure': 'Apparent Volume of Distribution (V/F) for Oral Midazolam', 'timeFrame': 'Pre-dose (-0.5 h) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 14 h pd on D2 and D18, and 22 h pd on D3 and D19'}, {'measure': 'Area Under the Plasma Concentration Time Curve from Time Zero to Time Tau, Where Tau is the Dosing Interval (AUC0-tau) for RO5186582 and RO5271857 (metabolite of RO5186582)', 'timeFrame': 'D18: Pre-dose -0.17 h (10 min) and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 12 h pd'}, {'measure': 'Cmax for RO5186582 and RO5271857 (metabolite of RO5186582)', 'timeFrame': 'Pre-dose (10 min) and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 12 h pd on D18 (timepoints relative to oral midazolam dosing are (- 2 h 10 min), -1.5, -1, -0.5, 0 h pre-dose and 1, 2, 3, 4, 6, 8, and 10 h pd)'}, {'measure': 'Tmax for RO5186582 and RO5271857 (metabolite of RO5186582)', 'timeFrame': 'Pre-dose (10 min) and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 12 h pd on D18 (timepoints relative to oral midazolam dosing are (- 2 h 10 min), -1.5, -1, -0.5, 0 h pre-dose and 1, 2, 3, 4, 6, 8, and 10 h pd)'}, {'measure': 'Metabolic Ratio Based on AUC0-inf for IV Midazolam', 'timeFrame': 'Pre-dose (-10 min) and 0.08 (5 min), 0.25 (15 min), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 14 h pd on D1 and D17, and 22 h pd on D2 and D18'}, {'measure': 'Change From Baseline in Event-Related Potential (ERP) parameters Using Oddball Auditory', 'timeFrame': 'D-1 (Baseline) and D16 at 1 and 4 h pd, time-matched to planned time, and D2 and D8 at 1 and 4 h pd'}, {'measure': 'Change from Baseline in Electroencephalogram (EEG) Parameters', 'timeFrame': 'D-1 (Baseline) and D16 at 1 and 4 h pd, time-matched to planned time, and D2 and D8 at 1 and 4 h pd'}, {'measure': 'Change From Baseline in Saccadic Eye Movement (SEM) Parameters', 'timeFrame': 'D-1 (Baseline) and D16 at 1 h pd, time-matched to planned time, and D2 and D18 at 1 h pd'}, {'measure': 'Change From Baseline in Attention and Memory of Selected Domains of Repeatable Battery for the Assessment of Neuropyschological Status (RBANSTM)', 'timeFrame': 'D-1 (Baseline) and D16 at 2 and 5 h pd, time-matched to planned time, and D2 and D18 at 2 and 5 h pd'}, {'measure': 'Change from Baseline in Concentration of 4 Beta-Hydroxy Cholesterol', 'timeFrame': 'D1 (Baseline) and D17'}, {'measure': 'Area Under the Plasma Concentration Time Curve from Zero to Infinity (AUC0-inf) for Oral and IV Midazolam', 'timeFrame': 'Midazolam (MDZ)-oral: pre-dose (-0.5 h) and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 14 h pd on D2 and 18, and 22 h pd on D3 and 19; MDZ-IV: Pre-dose (-10 min) and 5, 15 min, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 14 h pd on D1 and 17, and 22 h pd on D2 and 18'}, {'measure': 'Cmax for IV Midazolam', 'timeFrame': 'Pre-dose (-10 min) and 5, 15 min, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 14 h pd on D1 and 17, and 22 h pd on D2 and 18'}, {'measure': 'Area Under the Plasma Concentration Time Curve from Zero to Last Measurable Concentration (AUC[0-last]) for Oral and IV Midazolam', 'timeFrame': 'MDZ-oral: pre-dose (-0.5 h) and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 14 h pd on D2 and 18, and 22 h pd on D3 and 19; MDZ-IV: Pre-dose (-10 min) and 5, 15 min, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 14 h pd on D1 and 17, and 22 h pd on D2 and 18'}, {'measure': 'Time to Maximum Observed Concentration (Tmax) for Oral and IV Midazolam', 'timeFrame': 'MDZ-oral: pre-dose (-0.5 h) and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 14 h pd on D2 and 18, and 22 h pd on D3 and 19; MDZ-IV: Pre-dose (-10 min) and 5, 15 min, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 14 h pd on D1 and 17, and 22 h pd on D2 and 18'}, {'measure': 'Terminal Elimination Half-Life (t1/2) for Oral and IV Midazolam', 'timeFrame': 'MDZ-oral: pre-dose (-0.5 h) and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10 and 14 h pd on D2 and 18, and 22 h pd on D3 and 19; MDZ-IV: Pre-dose (-10 min) and 5, 15 min, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 14 h pd on D1 and 17, and 22 h pd on D2 and 18'}, {'measure': 'Apparent Clearence (CL/F) for Oral Midazolam', 'timeFrame': 'Pre-dose (-0.5 h) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 14 h pd on D2 and D18, and 22 h pd on D3 and D19'}]}, 'conditionsModule': {'conditions': ['Healthy Volunteer']}, 'descriptionModule': {'briefSummary': 'This is a non-randomized, open-label, five treatment, fixed sequence cross-over study to investigate the effect of RO5186582 treatment on CYP3A activity using midazolam as a probe CYP3A substrate, and also to assess the pharmacodynamic measures of brain electrical activity and sedation to explore the pharmacodynamic interaction between the gama-amino butyric acid (GABA)A negative allosteric modulator RO5186582 and the prototypical GABAA positive allosteric modulator midazolam. The anticipated study duration is up to nine weeks.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Healthy participants with signed informed consent.\n\nExclusion Criteria:\n\n* A history of epilepsy, convulsions or significant head injury\n* Significant history of drug allergy, as determined by the Investigator, or a known hypersensitivity to any of the ingredients of any of the study treatments\n* Use of any drugs or substances, including herbal treatments such as St John's Wort, that are known to be substrates, inducers or inhibitors of CYP3A4 within 30 days of the first dose administration\n* Pregnant or lactating\n* Any other clinically relevant abnormalities, concomitant diseases or ongoing medical conditions"}, 'identificationModule': {'nctId': 'NCT02254759', 'briefTitle': 'A Study of RO5186582 Treatment on Cytochrome P450 (CYP) 3A4 Activity in Healthy Participants', 'organization': {'class': 'INDUSTRY', 'fullName': 'Hoffmann-La Roche'}, 'orgStudyIdInfo': {'id': 'WP29393'}, 'secondaryIdInfos': [{'id': '2014-001850-41', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'OTHER', 'label': 'IV Midazolam Alone', 'description': 'A single 1 milligram (mg) dose of IV Midazolam on Day 1.', 'interventionNames': ['Drug: Midazolam, IV']}, {'type': 'OTHER', 'label': 'Oral Midazolam Alone', 'description': 'A single 5 mg oral dose of midazolam on Day 2.', 'interventionNames': ['Drug: Midazolam, oral']}, {'type': 'EXPERIMENTAL', 'label': 'RO5186582 Alone', 'description': 'RO5186582 240 mg oral tablet twice daily (BID) for 14 days from Days 3 to 16.', 'interventionNames': ['Drug: RO5186582']}, {'type': 'EXPERIMENTAL', 'label': 'RO5186582 Plus IV Midazolam', 'description': 'RO5186582 240 mg BID oral tablet in combination with a single 1 mg IV dose of midazolam on Day 17.', 'interventionNames': ['Drug: Midazolam, IV', 'Drug: RO5186582']}, {'type': 'EXPERIMENTAL', 'label': 'RO5186582 Plus Oral Midazolam', 'description': 'RO5186582 240 mg BID in combination with a single 5 mg oral dose of midazolam on Day 18.', 'interventionNames': ['Drug: Midazolam, oral', 'Drug: RO5186582']}], 'interventions': [{'name': 'Midazolam, IV', 'type': 'DRUG', 'description': '2 milligrams per milliliter (mg/mL) midazolam solution for IV administration. For a 1 mg dose, the midazolam solution (0.5 mL of 2 mg/mL) will be injected at 2 milligrams per minute (mg/min).', 'armGroupLabels': ['IV Midazolam Alone', 'RO5186582 Plus IV Midazolam']}, {'name': 'Midazolam, oral', 'type': 'DRUG', 'description': '0.1 mg/mL midazolam for oral administration. For a 5 mg dose, participants will receive 50 mL of 0.1 mg/mL midazolam.', 'armGroupLabels': ['Oral Midazolam Alone', 'RO5186582 Plus Oral Midazolam']}, {'name': 'RO5186582', 'type': 'DRUG', 'description': 'RO5186582 120 mg film-coated release tablet.', 'armGroupLabels': ['RO5186582 Alone', 'RO5186582 Plus IV Midazolam', 'RO5186582 Plus Oral Midazolam']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'LS2 9LH', 'city': 'Leeds', 'country': 'United Kingdom', 'geoPoint': {'lat': 53.79648, 'lon': -1.54785}}], 'overallOfficials': [{'name': 'Clinical Trials', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Hoffmann-La Roche'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hoffmann-La Roche', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}