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

Effects of Concomitant Administration of BMS-986142 on the Single-dose Pharmacokinetics of Probe Substrates for CYP2C8, CYP2C9, CYP2C19, CYP3A4, and P-gp in Healthy Subjects

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Development, LP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Education Resource
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: May 3, 2016
• First Submitted That Met QC Criteria: May 3, 2016
• First Posted (Estimate): May 4, 2016

Study Record Updates

• Last Update Posted (Estimate): September 16, 2016
• Last Update Submitted That Met QC Criteria: September 15, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Cardiotonic Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Anti-Ulcer Agents; Proton Pump Inhibitors; Digoxin; Midazolam; Montelukast; Omeprazole; Flurbiprofen
• Other Study ID Numbers: IM006-031