Study to Investigate the Effect of BMS-986142 on the Pharmacokinetics (PK) of Methotrexate and Probe Substrate Cocktail in Healthy Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 8 February 2016
• Main ID: NCT02456844
• Date of registration: 27/05/2015
• Prospective Registration: No
• Primary sponsor: Bristol-Myers Squibb
• Public title: Study to Investigate the Effect of BMS-986142 on the Pharmacokinetics (PK) of Methotrexate and Probe Substrate Cocktail in Healthy Patients
• Scientific 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
• Date of first enrolment: May 2015
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02456844
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science
• Phase: Phase 1

Contacts

• Name: Thomas L Hunt, MD PhD
• Affiliation: PPD

Key inclusion & exclusion 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,.



Age minimum: 18 Years
Age maximum: 50 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142

Drug: Methotrexate, Leucovorin and BMS-986142

Primary Outcome(s)

Area under the plasma concentration-time curve from time zero extrapolated to infinite time, AUC(INF) [Time Frame: Days 1 through 10]

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]

Secondary Outcome(s)

Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight [Time Frame: Days 1 through 10]

Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight [Time Frame: Days 1 through 10]

Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight [Time Frame: Days 1 through 10]

Trough observed plasma concentration (For BMS-986142 only) [Time Frame: Days 1 through 10]

Apparent total body clearance (parents only), CLT/F [Time Frame: Days 1 through 10]

Time of maximum observed plasma concentration (Tmax) [Time Frame: Days 1 through 10]

Terminal plasma half-life (T-half) [Time Frame: Days 1 through 10]

Secondary ID(s)

IM006-003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors