A Study to Assess the Effect of Phenytoin on the Drug Levels of Afimetoran and the Effect of Afimetoran on the Drug Levels of Midazolam

An Open-label, Single-sequence, Drug-drug Interaction Study in Healthy Participants to Assess the Effect of Phenytoin on the Pharmacokinetics of a Single Oral Dose of Afimetoran (BMS-986256) (Part 1) and the Effect of Steady-state Afimetoran on the Pharmacokinetics of Midazolam (Part 2)

This study will consist of 2 parts. The study will evaluate whether administration of phenytoin impacts the single-dose drug levels of afimetoran and BMT-271199 (Part 1) and will evaluate whether multiple administrations of afimetoran impact the drug levels of midazolam and 1-hydroxymidazolam (Part 2).

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Afimetoran; Drug: Midazolam; Drug: Phenytoin

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Local Institution - 0001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body mass index (BMI) of 19.0 kilograms per meter squared (kg/m^2) to 32.0 kg/m2, inclusive, and body weight ≥ 55 kg, at screening.

Exclusion Criteria:

• Any significant acute or chronic medical illness or any other condition listed as a contraindication in the phenytoin (Part 1) or midazolam (Part 2) package inserts.
• History of seizure (including simple febrile seizure), epilepsy, severe head injury (including concussion), multiple sclerosis, or other known neurological condition which the investigator considers to be clinically significant.
• Current or recent (within 3 months of study intervention administration) GI disease that could impact upon the absorption of study intervention.

Other protocol-defined inclusion/exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Afimetoran followed by phenytoin + afimetoran	Drug: Afimetoran; Specified dose on specified days; Other Names: BMS-986256; Drug: Phenytoin; Specified dose on specified days
Experimental: Part 2: Midazolam followed by afimetoran + midazolam	Drug: Afimetoran; Specified dose on specified days; Other Names: BMS-986256; Drug: Midazolam; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma concentration (Cmax)	Parts 1 and 2	Up to 53 days
Area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration (AUC[0-T])	Parts 1 and 2	Up to 53 days
Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC[INF])	Parts 1 and 2	Up to 53 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to attain maximum observed plasma concentration (Tmax)	Parts 1 and 2	Up to 53 days
Terminal half-life (T-Half)	Parts 1 and 2	Up to 53 days
Apparent total body clearance of the drug from the plasma (CLT/F)	Parts 1 and 2	Up to 53 days
Number of participants with adverse events (AEs)	Parts 1 and 2	Up to 124 days
Number of participants with clinical laboratory abnormalities	Parts 1 and 2	Up to 66 days
Number of participants with physical examination abnormalities	Parts 1 and 2	Up to 66 days
Number of participants with vital sign abnormalities	Parts 1 and 2	Up to 66 days
Number of participants with electrocardiogram (ECG) abnormalities	Parts 1 and 2	Up to 66 days

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2023
• Primary Completion (Actual): April 11, 2024
• Study Completion (Actual): April 11, 2024

Study Registration Dates

• First Submitted: June 5, 2023
• First Submitted That Met QC Criteria: June 5, 2023
• First Posted (Actual): June 13, 2023

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Midazolam; BMS-986256; Afimetoran; CYP3A4; Phenytoin
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Midazolam; Phenytoin
• Other Study ID Numbers: IM026-026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myers Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html

Drug and device information, study documents

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