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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Rheumatoid Arthritis

Treatments: Drug: Leucovorin; Drug: BMS-986195; Drug: Caffeine; Drug: Montelukast; Drug: Methotrexate; Drug: Pravastatin; Drug: Digoxin; Drug: Omeprazole; Drug: Midazolam; Drug: Flurbiprofen

Study type: Interventional

Funder types: Industry

Identifiers

NCT03131973

IM014-013

Details and patient eligibility

About

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.

Enrollment: 26 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

Methotrexate

Experimental group

Description:

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

Treatment:

Drug: Leucovorin

Drug: BMS-986195

Drug: Methotrexate

Cytochrome P450 and Transporter Substrates

Experimental group

Description:

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.

Treatment:

Drug: Pravastatin

Drug: BMS-986195

Drug: Flurbiprofen

Drug: Caffeine

Drug: Digoxin

Drug: Midazolam

Drug: Omeprazole

Drug: Montelukast