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

NCT02456844 | Completed Phase 1

• 1 other identifier: IM006-003
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• Time of maximum observed plasma concentration (Tmax)

  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

• 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

Study Arms (2)

Group 1

EXPERIMENTAL

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

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

Group 2

EXPERIMENTAL

Methotrexate,Leucovorin and BMS-986142

Drug: Methotrexate, Leucovorin and BMS-986142

Interventions

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

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.

Group 1

Methotrexate, Leucovorin and BMS-986142 DRUG

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.

Group 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• \. Healthy male subjects as determined by medical history, and clinical assessments.

You may not qualify if:

• 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,.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

montelukast; Flurbiprofen; Midazolam; Digoxin; Pravastatin; Methotrexate; Leucovorin

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Aminopterin; Pterins; Pteridines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Enzymes and Coenzymes

Study Officials

• Thomas L Hunt, MD PhD

  PPD Development, LP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: May 29, 2015
• Study Start: May 1, 2015
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: February 1, 2016

Record last verified: 2016-01