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

Phase 1

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: BMS-986142 200mg; Drug: BMS Drug-drug interaction cocktail (montelukast, flurbiprofen, omeprazole, midazolam, and digoxin); Drug: BMS-986142 350mg

• Registration Number: NCT02762123
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05
• Study First Submitted: 2016-05-03
• Study First Submitted QC: 2016-05-03
• Study First Posted: 2016-05-04
• Primary Completion: 2016-08
• Study Completion: 2016-08
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-15
• Last Update Posted: 2016-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1 (BMS-986142: 200 mg)	BMS-986142 200mg	200mg BMS-986142 administered orally once daily on specified days.
Cohort 1 (BMS-986142: 200 mg)	BMS Drug-drug interaction cocktail (montelukast, flurbiprofen, omeprazole, midazolam, and digoxin)	200mg BMS-986142 administered orally once daily on specified days.
Cohort 2 (BMS-986142: 350 mg)	BMS Drug-drug interaction cocktail (montelukast, flurbiprofen, omeprazole, midazolam, and digoxin)	350mg BMS-986142 administered orally once daily on specified days.
Cohort 2 (BMS-986142: 350 mg)	BMS-986142 350mg	350mg BMS-986142 administered orally once daily on specified days.

Primary Outcome Measures

Name	Time	Method
Maximum observed plasma concentration (Cmax) of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin.	57 samples up to day 26
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T))of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin	57 samples up to day 26
Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) of montelukast, flurbiprofen, omeprazole, midazolam, and digoxin	57 samples up to day 26

Secondary Outcome Measures

Name	Time	Method
Safety endpoints include the incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and death	Days 1-26; for SAEs up to 30 days post discontinuation of dosing

Trial Locations

Locations (1)

Ppd Development, Lp; 🇺🇸 Austin, Texas, United States