Effects of Concomitant Administration of BMS-986195 on Methotrexate, Caffeine, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin

Study Overview
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Brief Summary
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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.

Official Title
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Effects of Concomitant Administration of BMS-986195 on the Single-dose Pharmacokinetics of Methotrexate and Probe Substrates for Cytochrome P450 1A2, 2C8, 2C9, 2C19, 3A4, Organic Anion Transporter Polypeptide 1B1 and P-glycoprotein in Healthy Participants

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: BMS-986195
* Drug: Methotrexate
* Drug: Leucovorin
* Drug: Caffeine
* Drug: Montelukast
* Drug: Flurbiprofen
* Drug: Omeprazole
* Drug: Midazolam
* Drug: Digoxin
* Drug: Pravastatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methotrexate<br>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 | Drug: BMS-986195<br>* Specified dose on specified days<br>Drug: Methotrexate<br>* Specified dose on specified days<br>Drug: Leucovorin<br>* Specified dose on specified days<br>|
| Experimental: Cytochrome P450 and Transporter Substrates<br>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. | Drug: BMS-986195<br>* Specified dose on specified days<br>Drug: Caffeine<br>* Specified dose on specified days<br>Drug: Montelukast<br>* Specified dose on specified days<br>Drug: Flurbiprofen<br>* Specified dose on specified days<br>Drug: Omeprazole<br>* Specified dose on specified days<br>Drug: Midazolam<br>* Specified dose on specified days<br>Drug: Digoxin<br>* Specified dose on specified days<br>Drug: Pravastatin<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) | Measured by plasma concentrations | Up to 26 days | 
| Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T)) | Measured by plasma concentrations | Up to 26 days | 
| Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) | Measured by plasma concentrations | Up to 26 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Measured by investigator assessment | Up to 28 days | 
| Number of participants with serious adverse events | Measured by investigator assessment | Up to 45 days | 
| Number of participants with adverse events leading to discontinuation | Measured by investigator assessment | Up to 28 days | 
| Number of participants with clinical laboratory test abnormalities |  | Up to 28 days | 
| Number of participants with vital sign measurement abnormalities |  | Up to 28 days | 
| Number of participants with electrocardiogram abnormalities |  | Up to 28 days | 
| Number of participants with physical examination abnormalities |  | Up to 28 days | 
| Number of participants with marked abnormalities in clinical laboratory test results |  | Up to 28 days |