Rheumatoid Arthritis
Conditions
Brief summary
To study the Pharmacokinetics (PK) parameters of montelukast, flurbiprofen, midazolam, digoxin, pravastatin, and MTX when coadministered with BMS-986142.
Interventions
DRUGMontelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142
1. Montelukast 10-mg tablet: On Days 1 and 8,Single oral dose 2. Flurbiprofen 50-mg tablet: On Days 1 and 8,Single oral dose 3. Midazolam syrup 2.5 mL × 2 mg/mL (5 mg): On Days 1 and 8,Single oral dose 4. Digoxin (Lanoxin®) 0.25 mg tablet: On Days 1 and 8,Single oral dose 5. Pravastatin 40-mg tablet: On Days 1 and 8,Single oral dose 6. BMS-986142: On Days 6 through 12.
DRUGMethotrexate, Leucovorin and BMS-986142
1. Methotrexate (MTX) single oral dose of 3 × 2.5-mg tablet (Days 1 and 8) 2. Leucovorin single oral dose of 15-mg tablet (Days 2 and 9; 24 hours after MTX administration) 3. BMS-986142 on Days 6 through 10.
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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,.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum observed plasma concentration (Cmax) | Days 1 through 10 |
| Area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration, AUC(0-T) | Days 1 through 10 |
| Area under the plasma concentration-time curve from time zero extrapolated to infinite time, AUC(INF) | Days 1 through 10 |
Secondary
| Measure | Time frame |
|---|---|
| Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight | Days 1 through 10 |
| Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight | Days 1 through 10 |
| Time of maximum observed plasma concentration (Tmax) | Days 1 through 10 |
| Trough observed plasma concentration (For BMS-986142 only) | Days 1 through 10 |
| Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight | Days 1 through 10 |
| Terminal plasma half-life (T-half) | Days 1 through 10 |
| Apparent total body clearance (parents only), CLT/F | Days 1 through 10 |
Outcome results
None listed