Effects of Concomitant Administration of BMS-986195 on Methotrexate, Caffeine, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin

Effects of Concomitant Administration of BMS-986195 on the Single-dose Pharmacokinetics of Methotrexate and Probe Substrates for Cytochrome P450 1A2, 2C8, 2C9, 2C19, 3A4, Organic Anion Transporter Polypeptide 1B1 and P-glycoprotein in Healthy Participants

Drug-drug interaction study in healthy men and women not of childbearing potential. Assess the effect of BMS-986195 on the pharmacokinetics of methotrexate, caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin. Collect data on safety of BMS-986195 and methotrexate, caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin. Collect data on multiple-dose pharmacodynamics of BMS-986195.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Leucovorin; Drug: Methotrexate; Drug: Digoxin; Drug: BMS-986195; Drug: Caffeine; Drug: Montelukast; Drug: Flurbiprofen; Drug: Omeprazole; Drug: Midazolam; Drug: Pravastatin

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Development, LP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female (not of childbearing potential) participants as determined by medical and surgical history and assessments
• Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive
• Normal kidney function at screening

Exclusion Criteria:

• History of chronic headaches (eg, migraines, cluster headaches), defined as occurring 15 days or more a month, over the previous 3 months
• History of headaches related to caffeine withdrawal, including energy drinks
• History of syncope, orthostatic instability, or recurrent dizziness

Other protocol defined inclusion and exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methotrexate; Methotrexate single oral dose followed by leucovorin single oral dose on specified days followed by BMS-986195 coadministered with methotrexate single oral dose followed by leucovorin single oral dose on specified days	Drug: Leucovorin; Specified dose on specified days; Drug: Methotrexate; Specified dose on specified days; Drug: BMS-986195; Specified dose on specified days
Experimental: Cytochrome P450 and Transporter Substrates; Caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days, BMS-986195 multiple oral dose administration on specified days, and BMS-986195 coadministered with caffeine, montelukast, flurbiprofen, omeprazole, midazolam, digoxin, and pravastatin single oral dose on specified days.	Drug: Digoxin; Specified dose on specified days; Drug: BMS-986195; Specified dose on specified days; Drug: Caffeine; Specified dose on specified days; Drug: Montelukast; Specified dose on specified days; Drug: Flurbiprofen; Specified dose on specified days; Drug: Omeprazole; Specified dose on specified days; Drug: Midazolam; Specified dose on specified days; Drug: Pravastatin; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax)	Measured by plasma concentrations	Up to 26 days
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T))	Measured by plasma concentrations	Up to 26 days
Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF))	Measured by plasma concentrations	Up to 26 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with clinical laboratory test abnormalities		Up to 28 days
Number of participants with physical examination abnormalities		Up to 28 days
Number of participants with adverse events	Measured by investigator assessment	Up to 28 days
Number of participants with serious adverse events	Measured by investigator assessment	Up to 45 days
Number of participants with adverse events leading to discontinuation	Measured by investigator assessment	Up to 28 days
Number of participants with vital sign measurement abnormalities		Up to 28 days
Number of participants with electrocardiogram abnormalities		Up to 28 days
Number of participants with marked abnormalities in clinical laboratory test results		Up to 28 days

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2017
• Primary Completion (Actual): November 5, 2017
• Study Completion (Actual): November 10, 2017

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: April 25, 2017
• First Posted (Actual): April 27, 2017

Study Record Updates

• Last Update Posted (Actual): December 15, 2017
• Last Update Submitted That Met QC Criteria: December 13, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Purinergic Antagonists; Purinergic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Cardiotonic Agents; Dermatologic Agents; Micronutrients; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Protein Kinase Inhibitors; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Vitamins; Reproductive Control Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Antidotes; Vitamin B Complex; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Digoxin; Midazolam; Montelukast; Leucovorin; Methotrexate; Pravastatin; Branebrutinib; Caffeine; Omeprazole; Flurbiprofen
• Other Study ID Numbers: IM014-013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No