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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Itraconazole; Drug: BMS-986166; Drug: Extended Phenytoin Sodium; Drug: Gemfibrozil

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2021
• Primary Completion (Actual): April 27, 2022
• Study Completion (Actual): April 27, 2022

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 9, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Healthy Participants; BMS-986166
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites; Hormones, Hormone Substitutes, and Hormone Antagonists; Hypolipidemic Agents; Lipid Regulating Agents; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C8 Inhibitors; Itraconazole; Gemfibrozil; Phenytoin
• Other Study ID Numbers: IM018-004

Drug and device information, study documents

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