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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02456844
• Other study ID #: IM006-003
• Status: Completed
• Phase: Phase 1
• First received: May 27, 2015
• Last updated: January 29, 2016
• Start date: May 2015
• Est. completion date: July 2015

Study information

• Verified date: January 2016
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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,.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142
Montelukast 10-mg tablet: On Days 1 and 8,Single oral dose Flurbiprofen 50-mg tablet: On Days 1 and 8,Single oral dose Midazolam syrup 2.5 mL × 2 mg/mL (5 mg): On Days 1 and 8,Single oral dose Digoxin (Lanoxin®) 0.25 mg tablet: On Days 1 and 8,Single oral dose Pravastatin 40-mg tablet: On Days 1 and 8,Single oral dose BMS-986142: On Days 6 through 12.
• Methotrexate, Leucovorin and BMS-986142
Methotrexate (MTX) single oral dose of 3 × 2.5-mg tablet (Days 1 and 8) Leucovorin single oral dose of 15-mg tablet (Days 2 and 9; 24 hours after MTX administration) BMS-986142 on Days 6 through 10.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed plasma concentration (Cmax)		Days 1 through 10	No
Primary	Area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration, AUC(0-T)		Days 1 through 10	No
Primary	Area under the plasma concentration-time curve from time zero extrapolated to infinite time, AUC(INF)		Days 1 through 10	No
Secondary	Time of maximum observed plasma concentration (Tmax)		Days 1 through 10	No
Secondary	Terminal plasma half-life (T-half)		Days 1 through 10	No
Secondary	Apparent total body clearance (parents only), CLT/F		Days 1 through 10	No
Secondary	Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight		Days 1 through 10	No
Secondary	Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight		Days 1 through 10	No
Secondary	Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight		Days 1 through 10	No
Secondary	Trough observed plasma concentration (For BMS-986142 only)		Days 1 through 10	No