A Study to Assess the Effect of Itraconazole, Phenytoin and Gemfibrozil on the Drug Levels of BMS-986166 in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of itraconazole, phenytoin and gemfibrozil on the drug levels of BMS-986166 and its active metabolite BMT-121795. Participants will be randomly assigned to one of four groups and will remain in the study clinic for the duration of treatment.

Official Title
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A Phase 1, Single-Center, Parallel-Group, Open-Label, Randomized, Drug-Drug Interaction Study to Assess the Effect of Itraconazole, Phenytoin, and Gemfibrozil on the Pharmacokinetics of a Single Oral Dose of BMS-986166 in Healthy Participants

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: BMS-986166
* Drug: Itraconazole
* Drug: Extended Phenytoin Sodium
* Drug: Gemfibrozil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight of at least 55 kg. Body mass index (BMI) of 19.0 to 32.0 kg/m², inclusive. BMI = weight (kg)/(height [m])². Healthy female subjects of non-childbearing potential, or male subjects, as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory evaluations. Exclusion Criteria: Any significant acute or chronic medical illness or any other condition listed as a contraindication in the itraconazole, phenytoin, or gemfibrozil package inserts. History of any type of heart disease, including ischemia, infarction, clinically significant arrhythmias, sinus syndrome, hypertension, symptomatic orthostatic hypotension, atrioventricular block of any degree, bradycardia, syncope, clinically significant 12-lead ECG abnormalities, or any congenital heart disease. History of stroke or transient ischemic attacks. History of asthma or chronic obstructive pulmonary disease diagnosed or treated within the past 5 years. Other protocol-defined inclusion/exclusion criteria apply

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMS-986166<br> | Drug: BMS-986166<br>* Specified dose on specified days<br>|
| Experimental: BMS-986166 + Itraconazole<br> | Drug: BMS-986166<br>* Specified dose on specified days<br>Drug: Itraconazole<br>* Specified dose on specified days<br>* Other names: Sporanox;|
| Experimental: BMS-986166 + Phenytoin<br> | Drug: BMS-986166<br>* Specified dose on specified days<br>Drug: Extended Phenytoin Sodium<br>* Specified dose on specified days<br>* Other names: Dilantin;|
| Experimental: BMS-986166 + Gemfibrozil<br> | Drug: BMS-986166<br>* Specified dose on specified days<br>Drug: Gemfibrozil<br>* Specified dose on specified days<br>* Other names: Lopid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) of BMS-986166 |  | Up to Day 22 | 
| Cmax of BMT-121795 |  | Up to Day 22 | 
| Time of maximum observed plasma concentration (Tmax) of BMS-986166 |  | Up to Day 22 | 
| Tmax of BMT-121795 |  | Up to Day 22 | 
| Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) of BMS-986166 |  | Up to Day 22 | 
| AUC(0-T) of BMT-121795 |  | Up to Day 22 | 
| Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(INF))of BMS-986166 |  | Up to Day 22 | 
| AUC(INF) of BMT-121795 |  | Up to Day 22 | 
| Terminal plasma half-life (T-HALF) of BMS-986166 |  | Up to Day 22 | 
| T-HALF of BMT-121795 |  | Up to Day 22 | 
| Apparent total body clearance (CL/F) of BMS-986166 |  | Up to Day 22 | 
| Apparent volume of distribution (Vz/F) of BMS-986166 |  | Up to Day 22 | 
| Ratio of BMT-121795 Cmax to parent Cmax corrected for molecular weight (MR_Cmax) |  | Up to Day 22 | 
| Ratio of BMT-121795 AUC(0-T) to parent AUC(0-T) corrected for molecular weight (MR_AUC(0-T)) |  | Up to Day 22 | 
| Ratio of BMT-121795 AUC(INF) to parent AUC(INF) corrected for molecular weight (MR_AUC(INF)) |  | Up to Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events (AEs) |  | Up to Day 55 | 
| Number of participants with Serious Adverse Events (SAEs) |  | Up to Day 55 | 
| Number of participants with physical examination abnormalities |  | Up to Day 55 | 
| Number of participants with clinically significant changes in vital signs: Body temperature |  | Up to Day 55 | 
| Number of participants with clinically significant changes in vital signs: Respiratory rate |  | Up to Day 55 | 
| Number of participants with clinically significant changes in vital signs: Blood pressure |  | Up to Day 55 | 
| Number of participants with clinically significant changes in vital signs: Heart rate |  | Up to Day 55 | 
| Number of participants with clinically significant changes in ECG parameters: PR interval | PR interval is the time from the onset of the P wave to the start of the QRS complex | Up to Day 55 | 
| Number of participants with clinically significant changes in ECG parameters: QRS | QRS can be defined as the electrical impulse as it spreads through the ventricles, indicating ventricular depolarization | Up to Day 55 | 
| Number of participants with clinically significant changes in ECG parameters: QT interval | The QT interval is the time from the start of the Q wave to the end of the T wave | Up to Day 55 | 
| Number of participants with clinically significant changes in ECG parameters: QTcF | QTcF = Corrected QT interval using the Fridericia formula. QT interval is the time from the start of the Q wave to the end of the T wave | Up to Day 55 | 
| Number of participants with clinically significant changes in laboratory values: Hematology tests |  | Up to Day 55 | 
| Number of participants with clinically significant changes in laboratory values: Chemistry tests |  | Up to Day 55 | 
| Number of participants with clinically significant changes in laboratory values: Urinalysis |  | Up to Day 55 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Participants, BMS-986166