Hepatitis C
Conditions
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.
Interventions
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 |
| 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 | 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 | — |
| Apparent total oral clearance (CLT/F) of BMS-791325, BMS-794712, and BMS-948158 | 43 timepoints up to day 26 | — |
Countries
United States
Outcome results
None listed