Effects of Concomitant Administration of BMS-986195 on Methotrexate, Caffeine, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin
Phase 1
Completed
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT03131973
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Drug-drug interaction study in healthy men and women not of childbearing potential. Assess the effect of BMS-986195 on the pharmacokinetics of methotrexate, caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin. Collect data on safety of BMS-986195 and methotrexate, caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin. Collect data on multiple-dose pharmacodynamics of BMS-986195.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
Inclusion Criteria
- Healthy male and female (not of childbearing potential) participants as determined by medical and surgical history and assessments
- Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive
- Normal kidney function at screening
Exclusion Criteria
- History of chronic headaches (eg, migraines, cluster headaches), defined as occurring 15 days or more a month, over the previous 3 months
- History of headaches related to caffeine withdrawal, including energy drinks
- History of syncope, orthostatic instability, or recurrent dizziness
Other protocol defined inclusion and exclusion criteria could apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cytochrome P450 and Transporter Substrates Montelukast Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days. Methotrexate BMS-986195 Methotrexate single oral dose followed by leucovorin single oral dose on specified days followed by BMS-986195 coadministered with methotrexate single oral dose followed by leucovorin single oral dose on specified days Cytochrome P450 and Transporter Substrates Digoxin Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days. Methotrexate Methotrexate Methotrexate single oral dose followed by leucovorin single oral dose on specified days followed by BMS-986195 coadministered with methotrexate single oral dose followed by leucovorin single oral dose on specified days Methotrexate Leucovorin Methotrexate single oral dose followed by leucovorin single oral dose on specified days followed by BMS-986195 coadministered with methotrexate single oral dose followed by leucovorin single oral dose on specified days Cytochrome P450 and Transporter Substrates Caffeine Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days. Cytochrome P450 and Transporter Substrates Omeprazole Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days. Cytochrome P450 and Transporter Substrates Flurbiprofen Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days. Cytochrome P450 and Transporter Substrates Midazolam Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days. Cytochrome P450 and Transporter Substrates Pravastatin Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days. Cytochrome P450 and Transporter Substrates BMS-986195 Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days.
- Primary Outcome Measures
Name Time Method Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) Up to 26 days Measured by plasma concentrations
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T)) Up to 26 days Measured by plasma concentrations
Maximum observed plasma concentration (Cmax) Up to 26 days Measured by plasma concentrations
- Secondary Outcome Measures
Name Time Method Number of participants with serious adverse events Up to 45 days Measured by investigator assessment
Number of participants with adverse events leading to discontinuation Up to 28 days Measured by investigator assessment
Number of participants with marked abnormalities in clinical laboratory test results Up to 28 days Number of participants with adverse events Up to 28 days Measured by investigator assessment
Number of participants with vital sign measurement abnormalities Up to 28 days Number of participants with clinical laboratory test abnormalities Up to 28 days Number of participants with physical examination abnormalities Up to 28 days Number of participants with electrocardiogram abnormalities Up to 28 days
Trial Locations
- Locations (1)
PPD Development, LP
🇺🇸Austin, Texas, United States