Clinical trial NCT02084953: Study to Determine the Effect of BMS-791325 on the ECG QTcF Interval in Healthy Subjects
Official title: A Randomized, Double-Blinded, Positive-Controlled, Placebo-Controlled, 3-Way Crossover Study to Determine the Electrocardiographic Effects of BMS-791325 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2014-03-12
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Approximately 28 days
Secondary outcomes:
measure: ΔΔHR, ΔΔPR, ΔΔQRS, ΔΔQT
timeFrame: Approximately 28 days
measure: Number and percent of subjects having a within-period maximum HR, PR, QRS, QT, QTcF, ΔQT and ΔQTcF within prespecified categories
timeFrame: Approximately 28 days
measure: Relationship between plasma concentrations of BMS-791325, BMS-794712, and BMS-948158, and the corresponding ΔΔQTcF
timeFrame: Approximately 28 days
measure: Maximum observed concentration (Cmax) of BMS-791325, BMS-794712, and BMS-948158
timeFrame: 43 timepoints up to day 26
measure: Time of maximum observed concentration (Tmax) of BMS-791325, BMS-794712, and BMS-948158
timeFrame: 43 timepoints up to day 26
measure: Area under the concentration-time curve in one dosing interval (AUC(TAU)) of BMS-791325, BMS-794712, and BMS-948158
timeFrame: 43 timepoints up to day 26
measure: Apparent total oral clearance (CLT/F) of BMS-791325, BMS-794712, and BMS-948158
timeFrame: 43 timepoints up to day 26
measure: Terminal phase plasma half life (T-HALF) of BMS-791325, BMS-794712, and BMS-948158
timeFrame: 43 timepoints up to day 26
measure: AUC(TAU) metabolic ratios of BMS-791325, BMS-794712, and BMS-948158
timeFrame: 43 timepoints up to day 26
measure: 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
timeFrame: Up to day 28
measure: Difference from placebo of Moxifloxacin in change from baseline (Day -1) to Day 3 at postdose extraction times for the QTcF (ΔΔQTcF)
timeFrame: Approximately 28 days
Other outcomes:
Locations:
city: Austin
country: United States
facility: Ppd Development, Llc
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: