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

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03131973
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arms: 2
• Actual Duration (Months): 5.9
• Patients Per Site Per Month: 4.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: BMS-986195; Drug: Methotrexate; Drug: Leucovorin; Drug: Caffeine; Drug: Montelukast; Drug: Flurbiprofen; Drug: Omeprazole; Drug: Midazolam; Drug: Digoxin; Drug: Pravastatin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: May 13, 2017
• Actual Primary Completion Date: Nov 5, 2017
• Actual Study Completion Date: Nov 10, 2017

Arms and Interventions

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: BMS-986195; Specified dose on specified days; Drug: Methotrexate; Specified dose on specified days; Drug: Leucovorin; 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: 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: Digoxin; Specified dose on specified days; Drug: Pravastatin; Specified dose on specified days

Outcome Measures

Primary Outcome Measures

1. Maximum observed plasma concentration (Cmax) [Up to 26 days]

   Measured by plasma concentrations

2. Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T)) [Up to 26 days]

   Measured by plasma concentrations

3. Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) [Up to 26 days]

   Measured by plasma concentrations

Secondary Outcome Measures

1. Number of participants with adverse events [Up to 28 days]

   Measured by investigator assessment

2. Number of participants with serious adverse events [Up to 45 days]

   Measured by investigator assessment

3. Number of participants with adverse events leading to discontinuation [Up to 28 days]

   Measured by investigator assessment

4. Number of participants with clinical laboratory test abnormalities [Up to 28 days]

5. Number of participants with vital sign measurement abnormalities [Up to 28 days]

6. Number of participants with electrocardiogram abnormalities [Up to 28 days]

7. Number of participants with physical examination abnormalities [Up to 28 days]

8. Number of participants with marked abnormalities in clinical laboratory test results [Up to 28 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PPD Development, LP	Austin	Texas	United States	78744

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT03131973
• Other Study ID Numbers: IM014-013
• First Posted: Apr 27, 2017
• Last Update Posted: Dec 15, 2017
• Last Verified: Dec 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Leucovorin; Flurbiprofen; Methotrexate; Digoxin; Midazolam; Caffeine; Omeprazole; Pravastatin; Montelukast; Branebrutinib

Study Results

No Results Posted as of Dec 15, 2017