Study to Determine the Effect of BMS-791325 on the ECG QTcF Interval in Healthy Subjects
Phase 1
Completed
- Conditions
- Hepatitis C
- Interventions
- Registration Number
- NCT02084953
- Lead Sponsor
- Bristol-Myers Squibb
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 59
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description ARM A: BMS-791325 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 ARM C: Placebo matching BMS-791325 Placebo matching BMS-791325 Placebo matching BMS-791325 0 mg tablet orally once daily for 3 days ARM B: Moxifloxacin Moxifloxacin Moxifloxacin 400mg tablet orally once on third day
- Primary Outcome Measures
Name Time Method 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
Name Time Method ΔΔHR, ΔΔPR, ΔΔQRS, ΔΔQT Approximately 28 days 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
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 Adverse event (AEs)
Serious adverse event (SAEs)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
Trial Locations
- Locations (1)
Ppd Development, Llc
🇺🇸Austin, Texas, United States