NCT02456844CompletedPhase 1
Effects of BMS-986142 on the Single-dose Pharmacokinetics of Methotrexate and Probe Substrates Montelukast (CYP2C8), Flurbiprofen (CYP2C9), Midazolam (CYP3A4), Digoxin (P-gp), and Pravastatin (OATP1B1) in Healthy Subjects
Bristol-Myers Squibb0 sites24 target enrollmentStarted: May 2015Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 24
- Primary Endpoint
- Maximum observed plasma concentration (Cmax)
Study Overview
Brief Summary
To study the Pharmacokinetics (PK) parameters of montelukast, flurbiprofen, midazolam, digoxin, pravastatin, and MTX when coadministered with BMS-986142.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Groups 1 and 2:
- •Written informed consent from all subjects.
- •Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive
- •Non-smokers.
- •Normal renal function at screening as evidenced by an estimated glomerular filtration rate (GFR) of > 90 mL/min/1.73 m2 .
- •Subject reenrollment.
- •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 plus 5 half-lives of BMS-
- •Male subjects must be willing to refrain from sperm donation during the entire study plus 5 half-lives of BMS-
- •Group 1 only:
- •Healthy male and female (not of childbearing potential) subjects as determined by medical history, and clinical assessments.
- •Women must have documented proof that they are not of childbearing potential and must not be breast feeding.
- •Group 2 only:
- •Healthy male subjects as determined by medical history, and clinical assessments.
Exclusion Criteria
- •Administration of live vaccine including polio vaccine during the course of the study, 12 weeks prior to the first dose of study drug, or 30 days after the last dose of study drug.
- •Active tuberculosis (TB) requiring treatment within the previous 3 years.
- •History of herpes zoster.
- •Subjects who have experienced recent infection, upper respiratory infection,.
Arms & Interventions
Group 1
Experimental
Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142
Intervention: Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142 (Drug)
Group 2
Experimental
Methotrexate,Leucovorin and BMS-986142
Intervention: Methotrexate, Leucovorin and BMS-986142 (Drug)
Outcomes
Primary Outcomes
Maximum observed plasma concentration (Cmax)
Time Frame: Days 1 through 10
Area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration, AUC(0-T)
Time Frame: Days 1 through 10
Area under the plasma concentration-time curve from time zero extrapolated to infinite time, AUC(INF)
Time Frame: Days 1 through 10
Secondary Outcomes
- Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight(Days 1 through 10)
- Trough observed plasma concentration (For BMS-986142 only)(Days 1 through 10)
- Apparent total body clearance (parents only), CLT/F(Days 1 through 10)
- Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight(Days 1 through 10)
- Time of maximum observed plasma concentration (Tmax)(Days 1 through 10)
- Terminal plasma half-life (T-half)(Days 1 through 10)
- Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight(Days 1 through 10)
Investigators
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