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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

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ClinicalTrials.gov Identifier: NCT02456844
Recruitment Status : Completed
First Posted : May 29, 2015
Last Update Posted : February 1, 2016
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

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

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142 Drug: Methotrexate, Leucovorin and BMS-986142 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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 Start Date : May 2015
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015


Arm Intervention/treatment
Experimental: Group 1
Montelukast, Flurbiprofen, Midazolam, Digoxin, Pravastatin and BMS-986142
Drug: Montelukast, 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.

Experimental: Group 2
Methotrexate,Leucovorin and BMS-986142
Drug: Methotrexate, 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.




Primary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) [ Time Frame: Days 1 through 10 ]
  2. 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 ]
  3. Area under the plasma concentration-time curve from time zero extrapolated to infinite time, AUC(INF) [ Time Frame: Days 1 through 10 ]

Secondary Outcome Measures :
  1. Time of maximum observed plasma concentration (Tmax) [ Time Frame: Days 1 through 10 ]
  2. Terminal plasma half-life (T-half) [ Time Frame: Days 1 through 10 ]
  3. Apparent total body clearance (parents only), CLT/F [ Time Frame: Days 1 through 10 ]
  4. Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight [ Time Frame: Days 1 through 10 ]
  5. Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight [ Time Frame: Days 1 through 10 ]
  6. Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight [ Time Frame: Days 1 through 10 ]
  7. Trough observed plasma concentration (For BMS-986142 only) [ Time Frame: Days 1 through 10 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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,.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02456844


Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Principal Investigator: Thomas L Hunt, MD PhD PPD
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02456844    
Other Study ID Numbers: IM006-003
First Posted: May 29, 2015    Key Record Dates
Last Update Posted: February 1, 2016
Last Verified: January 2016
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Leucovorin
Flurbiprofen
Methotrexate
Digoxin
Midazolam
Pravastatin
Montelukast
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors