Study to Determine the Effect of BMS-791325 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 BMS-791325 has an effect on the electrocardiogram (ECG) interval QT corrected for Fridericia's method (QTcF).

Detailed Description
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Primary Purpose: Other: This Phase 1 study is a clinical pharmacology thorough QT study.

Official Title
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A Randomized, Double-Blinded, Positive-Controlled, Placebo-Controlled, 3-Way Crossover Study to Determine the Electrocardiographic Effects of BMS-791325 in Healthy Subjects

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: BMS-791325
* Drug: Moxifloxacin
* Drug: Placebo matching BMS-791325


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 men and women, ages 18 to 49 yr old BMI 18 to 32 Women must not be pregnant or breastfeeding Exclusion Criteria: Any significant acute or chronic medical illness 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 History of biliary disorders, including Gilbert's disease or Dubin-Johnson disease Inability to swallow multiple tablets consecutively 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, Heart Rate (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, BMS-791325, nonstructural protein 5B (NS5B) non-nucleoside inhibitors 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARM A: BMS-791325<br>BMS-791325 600 mg tablet orally on 1st and 2nd day, then 900 mg on the 3rd day once a day for 3 days | Drug: BMS-791325<br> <br> |
| Active Comparator: ARM B: Moxifloxacin<br>Moxifloxacin 400mg tablet orally once on third day | Drug: Moxifloxacin<br> <br> * Other names: Avelox®;|
| Placebo Comparator: ARM C: Placebo matching BMS-791325<br>Placebo matching BMS-791325 0 mg tablet orally once daily for 3 days | Drug: Placebo matching BMS-791325<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference from placebo of BMS-791325 in time-matched change from baseline (Day -1 on the study) to Day 3 of each period (ΔΔQTcF) at postdose extraction times for the QTcF |  | Approximately 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ΔΔHR, ΔΔPR, ΔΔQRS, ΔΔQT | Difference from placebo in time-matched change from baseline (Day -1) to Day 3 at postdose extraction times in the ECG-derived RR or HR and other ECG intervals (PR, QRS, QT). QT is the unadjusted QT interval | Approximately 28 days | 
| Number and percent of subjects having a within-period maximum HR, PR, QRS, QT, QTcF, ΔQT and ΔQTcF within prespecified categories |  | Approximately 28 days | 
| Relationship between plasma concentrations of BMS-791325, BMS-794712, and BMS-948158, and the corresponding ΔΔQTcF |  | Approximately 28 days | 
| Maximum observed concentration (Cmax) of BMS-791325, BMS-794712, and BMS-948158 |  | 43 timepoints up to day 26 | 
| Time of maximum observed concentration (Tmax) of BMS-791325, BMS-794712, and BMS-948158 |  | 43 timepoints up to day 26 | 
| Area under the concentration-time curve in one dosing interval (AUC(TAU)) of BMS-791325, BMS-794712, and BMS-948158 |  | 43 timepoints up to day 26 | 
| Apparent total oral clearance (CLT/F) of BMS-791325, BMS-794712, and BMS-948158 |  | 43 timepoints up to day 26 | 
| Terminal phase plasma half life (T-HALF) of BMS-791325, BMS-794712, and BMS-948158 |  | 43 timepoints up to day 26 | 
| AUC(TAU) metabolic ratios of BMS-791325, BMS-794712, and BMS-948158 |  | 43 timepoints up to day 26 | 
| Incidence of AEs, SAEs, AEs leading to discontinuation and death, marked laboratory abnormalities, findings on 12-lead safety ECG measurements and physical examination, and abnormalities in vital sign measurements exceeding pre-defined thresholds | Adverse event (AEs) Serious adverse event (SAEs) | Up to day 28 | 
| Difference from placebo of Moxifloxacin in change from baseline (Day -1) to Day 3 at postdose extraction times for the QTcF (ΔΔQTcF) |  | Approximately 28 days |