Study to Determine the Effect of BMS-791325 on the ECG QTcF Interval in Healthy Subjects

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

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).

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: BMS-791325; Drug: Moxifloxacin; Drug: Placebo matching BMS-791325

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • Ppd Development, Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARM A: BMS-791325; 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
Active Comparator: ARM B: Moxifloxacin; Moxifloxacin 400mg tablet orally once on third day	Drug: Moxifloxacin; Other Names: Avelox®
Placebo Comparator: ARM C: Placebo matching BMS-791325; Placebo matching BMS-791325 0 mg tablet orally once daily for 3 days	Drug: Placebo matching BMS-791325

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: March 10, 2014
• First Submitted That Met QC Criteria: March 10, 2014
• First Posted (Estimate): March 12, 2014

Study Record Updates

• Last Update Posted (Estimate): July 28, 2014
• Last Update Submitted That Met QC Criteria: July 25, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: AI443-112