A Study to Assess the Effect of BMS-986142 on Pharmacokinetics (PK) of Probe Substrates

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Rheumatoid Arthritis

Treatments: Drug: BMS Drug-drug interaction cocktail (montelukast, flurbiprofen, omeprazole, midazolam, and digoxin); Drug: BMS-986142 200mg; Drug: BMS-986142 350mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02762123

IM006-031

Details and patient eligibility

About

The study is being conducted to assess the effect of BMS-986142 on the single-dose PK parameters of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin, probe drugs for (cytochome P450) CYP2C8, CYP2C9, CYP2C19, CYP3A4, and P-glycoprotein (P-gp), respectively.

Enrollment: 28 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Signed Informed Consent
2. Target population: Healthy (current non-smokers) subjects as determined by medical history, surgical history, physical examination, vital signs, electrocardiogram (ECG), and clinical laboratory determinations.
3. Subjects with body mass index of 18 to 32 kg/m2, inclusive
4. Men, and women of nonchildbearing potential. Women must have documented proof that they are not of childbearing potential and must not be breastfeeding.
5. Males who are sexually active with women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of the study drug (3 days) plus 90 days (duration of sperm turnover) for a total of 93 days (approximately 14 weeks) after treatment completion. Female partners of male subjects are expected to use one of the highly effective methods of contraception listed in the protocol.

Exclusion criteria

1. History of any chronic or acute illness, recent infection, gastrointestinal disease, smoking and alcohol abuse, any significant drug allergy or allergy to digoxin, flurbiprofen, midazolam, omeprazole, or montelukast, Bruton's tyrosine kinase (BTK) inhibitors, immunologic or related compounds.
2. History of billiary disorder, asthma, bleeding disorder, cancer
3. Received live vaccine during last 12 weeks, active tuberculosis (TB) in last 3 years
4. Medical history indicative of an increased risk of arrhythmia.
5. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

Cohort 1 (BMS-986142: 200 mg)

Experimental group

Description:

200mg BMS-986142 administered orally once daily on specified days.

Treatment:

Drug: BMS-986142 200mg

Drug: BMS Drug-drug interaction cocktail (montelukast, flurbiprofen, omeprazole, midazolam, and digoxin)

Cohort 2 (BMS-986142: 350 mg)

Experimental group

Description:

350mg BMS-986142 administered orally once daily on specified days.

Treatment:

Drug: BMS-986142 350mg

Drug: BMS Drug-drug interaction cocktail (montelukast, flurbiprofen, omeprazole, midazolam, and digoxin)