Clinical trial NCT02456844: Study to Investigate the Effect of BMS-986142 on the Pharmacokinetics (PK) of Methotrexate and Probe Substrate Cocktail in Healthy Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2015-05-29
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: To study the Pharmacokinetics (PK) parameters of montelukast, flurbiprofen, midazolam, digoxin, pravastatin, and MTX when coadministered with BMS-986142.


Eligibility criteria: Inclusion Criteria:

Groups 1 and 2:

1. Written informed consent from all subjects.
2. Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive
3. Non-smokers.
4. Normal renal function at screening as evidenced by an estimated glomerular filtration rate (GFR) of \> 90 mL/min/1.73 m2 .
5. Subject reenrollment.
6. 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-986142.
7. Male subjects must be willing to refrain from sperm donation during the entire study plus 5 half-lives of BMS-986142.

Group 1 only:

1. Healthy male and female (not of childbearing potential) subjects as determined by medical history, and clinical assessments.
2. Women must have documented proof that they are not of childbearing potential and must not be breast feeding.

Group 2 only:

1. Healthy male subjects as determined by medical history, and clinical assessments.

Exclusion Criteria:

1. 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.
2. Active tuberculosis (TB) requiring treatment within the previous 3 years.
3. History of herpes zoster.
4. Subjects who have experienced recent infection, upper respiratory infection,.

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Days 1 through 10
measure: Area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration, AUC(0-T)
timeFrame: Days 1 through 10
measure: Area under the plasma concentration-time curve from time zero extrapolated to infinite time, AUC(INF)
timeFrame: Days 1 through 10
Secondary outcomes:
measure: Time of maximum observed plasma concentration (Tmax)
timeFrame: Days 1 through 10
measure: Terminal plasma half-life (T-half)
timeFrame: Days 1 through 10
measure: Apparent total body clearance (parents only), CLT/F
timeFrame: Days 1 through 10
measure: Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight
timeFrame: Days 1 through 10
measure: Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight
timeFrame: Days 1 through 10
measure: Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight
timeFrame: Days 1 through 10
measure: Trough observed plasma concentration (For BMS-986142 only)
timeFrame: Days 1 through 10
Other outcomes:
Locations:
Study officials:
affiliation: PPD Development, LP
name: Thomas L Hunt, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: