HIV/AIDS
Conditions
Brief summary
The purpose of this study is to determine whether multiple doses of Efavirenz has an effect on the QTc interval (corrected by Fridericia) in CYP2B6 \*1/\*6 and \*6/\*6 healthy subjects.
Detailed description
CYP = Cytochrome p-450 Primary Purpose: Other: This is a Phase 1 clinical pharmacology thorough QT study being conducted as a post marketing requirement
Interventions
DRUGMoxifloxacin
DRUGPlacebo
DRUGEfavirenz
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
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 volunteers, ages 18 to 49 years old * BMI 18 to 32 kg/m2 * Women must not be pregnant or breastfeeding
Exclusion criteria
* 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 * 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, 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, Efavirenz or related compounds
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference from placebo of Efavirenz (EFV) in change from period-specific baseline in the QT interval corrected for heart rate (HR) via Fridericia's method (QTcF) at postdose extraction times (ΔΔQTcF) | Days 1, 2, 5, 6, 19 and 20 | QTcF = QT corrected for Fridericia's formula |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference from placebo of Moxifloxacin in change from period-specific baseline in QTcF (ΔΔQTcF) following a single dose | Days 1, 5 and 19 | — |
| Number and percent of subjects having a maximum QTcF, HR, PR, and QRS outside of pre-specified categories and those having a maximum ΔQTcF outside of pre-specified categories | Days 1, 5 and 19 | — |
| Time of maximum observed plasma concentration (Tmax) of EFV | Days 1, 2, 19 and 20 | — |
| Difference from placebo of EFV in change from period-specific baseline in other ECG parameters: HR, PR, QRS, and uncorrected QT following 14 days of dosing | Days 1, 5 and 19 | ECG = Electrocardiogram |
| Trough observed plasma concentration 24 h after a dose (C24) of EFV | Days 1, 2, 19 and 20 | — |
| Area under the concentration-time curve in one dosing interval (AUC(TAU)) of EFV | Days 1, 2, 19 and 20 | — |
| Safety based on incidence of AEs, SAEs, AEs leading to discontinuation, marked laboratory abnormalities, findings on 12-lead safety ECG measurements and physical examinations, and abnormalities in vital sign measurements exceeding pre-defined thresholds | Up to 30 days after discontinuation of dose (approximately 52 days) | Serious AE (SAE) |
| Maximum observed plasma concentration (Cmax) of EFV | Days 1, 2, 19 and 20 | — |
Countries
United States
Outcome results
None listed