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Clinical Trials/NCT02084953
NCT02084953CompletedPhase 1

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

Bristol-Myers Squibb1 site in 1 country59 target enrollmentStarted: April 2014Last updated:
Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 1
Status
Completed
Sponsor
Enrollment
59
Locations
1
Primary Endpoint
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

Study Overview

Brief Summary

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

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

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Eligibility Criteria

Ages
18 Years to 49 Years (Adult)
Sex
All
Accepts Healthy Volunteers
Yes

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

Arms & Interventions

ARM A: BMS-791325

Experimental

BMS-791325 600 mg tablet orally on 1st and 2nd day, then 900 mg on the 3rd day once a day for 3 days

Intervention: BMS-791325 (Drug)

ARM B: Moxifloxacin

Active Comparator

Moxifloxacin 400mg tablet orally once on third day

Intervention: Moxifloxacin (Drug)

ARM C: Placebo matching BMS-791325

Placebo Comparator

Placebo matching BMS-791325 0 mg tablet orally once daily for 3 days

Intervention: Placebo matching BMS-791325 (Drug)

Outcomes

Primary Outcomes

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

Time Frame: Approximately 28 days

Secondary Outcomes

  • ΔΔHR, ΔΔPR, ΔΔQRS, ΔΔQT(Approximately 28 days)
  • 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)
  • 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)
  • 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(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)
  • Time of maximum observed concentration (Tmax) 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)

Investigators

Sponsor
Bristol-Myers Squibb
Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (1)

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