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

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

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

Methotrexate, Leucovorin and BMS-986142

About this trial

This is an interventional basic science trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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-986142.
Male subjects must be willing to refrain from sperm donation during the entire study plus 5 half-lives of BMS-986142.

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:

1. 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,.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Group 1

Group 2

Arm Description

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

Methotrexate,Leucovorin and BMS-986142

Outcomes

Primary Outcome Measures

Maximum observed plasma concentration (Cmax)

Area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration, AUC(0-T)

Area under the plasma concentration-time curve from time zero extrapolated to infinite time, AUC(INF)

Secondary Outcome Measures

Time of maximum observed plasma concentration (Tmax)

Terminal plasma half-life (T-half)

Apparent total body clearance (parents only), CLT/F

Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight

Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight

Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight

Trough observed plasma concentration (For BMS-986142 only)

Full Information

NCT ID

NCT02456844

First Posted

May 27, 2015

Last Updated

January 29, 2016

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT02456844

Brief Title

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

2. Study Status

Record Verification Date

January 2016

Overall Recruitment Status

Completed

Study Start Date

May 2015 (undefined)

Primary Completion Date

July 2015 (Actual)

Study Completion Date

July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1

Arm Type

Experimental

Arm Description

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

Arm Title

Group 2

Arm Type

Experimental

Arm Description

Methotrexate,Leucovorin and BMS-986142

Intervention Type

Drug

Intervention Name(s)

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

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Methotrexate, Leucovorin and BMS-986142

Intervention Description

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.

Primary Outcome Measure Information:

Title

Maximum observed plasma concentration (Cmax)

Time Frame

Days 1 through 10

Title

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

Title

Area under the plasma concentration-time curve from time zero extrapolated to infinite time, AUC(INF)

Time Frame

Days 1 through 10

Secondary Outcome Measure Information:

Title

Time of maximum observed plasma concentration (Tmax)

Time Frame

Days 1 through 10

Title

Terminal plasma half-life (T-half)

Time Frame

Days 1 through 10

Title

Apparent total body clearance (parents only), CLT/F

Time Frame

Days 1 through 10

Title

Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight

Time Frame

Days 1 through 10

Title

Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight

Time Frame

Days 1 through 10

Title

Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight

Time Frame

Days 1 through 10

Title

Trough observed plasma concentration (For BMS-986142 only)

Time Frame

Days 1 through 10

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

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-986142. Male subjects must be willing to refrain from sperm donation during the entire study plus 5 half-lives of BMS-986142. 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: 1. 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,.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas L Hunt, MD PhD

Organizational Affiliation

PPD

Official's Role

Principal Investigator

12. IPD Sharing Statement

Learn more about this trial

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

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