Study to Determine the Effect of Efavirenz on the ECG QTcF Interval in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to determine whether multiple doses of Efavirenz has an effect on the QTc interval (corrected by Fridericia) in CYP2B6 *1/*6 and *6/*6 healthy subjects.

Detailed Description
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CYP = Cytochrome p-450 Primary Purpose: Other: This is a Phase 1 clinical pharmacology thorough QT study being conducted as a post marketing requirement

Official Title
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A Study to Determine the Concentration-Electrocardiographic Effects of Efavirenz in Healthy Subjects Enriched for CYP2B6 Polymorphisms

Conditions
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HIV/AIDS

Intervention / Treatment
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* Drug: Moxifloxacin
* Drug: Placebo
* Drug: Efavirenz


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Healthy volunteers, ages 18 to 49 years old BMI 18 to 32 kg/m2 Women must not be pregnant or breastfeeding Exclusion Criteria: A personal history of clinically relevant cardiac disease, symptomatic or asymptomatic arrhythmias, presyncope or syncopal episodes, or additional risk factors for torsades de pointes (eg, heart failure) History of hypokalemia, personal history or family history of prolonged QT interval, or family history of sudden cardiac death at a young age Any of the following on 12-lead electrocardiogram (ECG) prior to study drug administration: PR ≥210 msec, QRS ≥120 msec, QT ≥500 msec, QTcF ≥450 msec, HR <45 bpm Second or third degree heart block prior to study drug Positive urine screen for drugs of abuse Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or Human Immunodeficiency Virus (HIV)-1, -2 antibody Any of the following lab results outside of the ranges specified below prior to dosing: Alanine aminotransferase (ALT) >upper limit of normal (ULN), aspartate aminotransferase (AST) >ULN, Total bilirubin >ULN, Direct bilirubin >ULN, Creatinine >ULN, Serum potassium <lower limit of normal (LLN), Serum magnesium <LLN History of allergy to Moxifloxacin, Efavirenz or related compounds

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moxifloxacin, Placebo, Efavirenz<br>Moxifloxacin, Placebo, Efavirenz single dose as specified | Drug: Moxifloxacin<br> <br> * Other names: Avelox®;Drug: Placebo<br> <br> Drug: Efavirenz<br> <br> * Other names: BMS-561525;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference from placebo of Efavirenz (EFV) in change from period-specific baseline in the QT interval corrected for heart rate (HR) via Fridericia's method (QTcF) at postdose extraction times (ΔΔQTcF) | QTcF = QT corrected for Fridericia's formula | Days 1, 2, 5, 6, 19 and 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference from placebo of EFV in change from period-specific baseline in other ECG parameters: HR, PR, QRS, and uncorrected QT following 14 days of dosing | ECG = Electrocardiogram | Days 1, 5 and 19 | 
| Difference from placebo of Moxifloxacin in change from period-specific baseline in QTcF (ΔΔQTcF) following a single dose |  | Days 1, 5 and 19 | 
| Number and percent of subjects having a maximum QTcF, HR, PR, and QRS outside of pre-specified categories and those having a maximum ΔQTcF outside of pre-specified categories |  | Days 1, 5 and 19 | 
| Time of maximum observed plasma concentration (Tmax) of EFV |  | Days 1, 2, 19 and 20 | 
| Maximum observed plasma concentration (Cmax) of EFV |  | Days 1, 2, 19 and 20 | 
| Trough observed plasma concentration 24 h after a dose (C24) of EFV |  | Days 1, 2, 19 and 20 | 
| Area under the concentration-time curve in one dosing interval (AUC(TAU)) of EFV |  | Days 1, 2, 19 and 20 | 
| Safety based on incidence of AEs, SAEs, AEs leading to discontinuation, marked laboratory abnormalities, findings on 12-lead safety ECG measurements and physical examinations, and abnormalities in vital sign measurements exceeding pre-defined thresholds | Serious AE (SAE) | Up to 30 days after discontinuation of dose (approximately 52 days) |