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

Study Overview
=================
Brief Summary
-----------------
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).

Official Title
-----------------
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)

Conditions
-----------------
Healthy Participants

Intervention / Treatment
-----------------
* Drug: Afimetoran
* Drug: Phenytoin
* Drug: Midazolam


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
BMS-986256, Afimetoran, Midazolam, CYP3A4, Phenytoin