Study to Determine the Effect of Efavirenz on the ECG QTcF Interval in Healthy Subjects
- Registration Number
- NCT02164812
- Lead Sponsor
- Bristol-Myers Squibb
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 58
Inclusion Criteria
- Healthy volunteers, ages 18 to 49 years old
- BMI 18 to 32 kg/m2
- Women must not be pregnant or breastfeeding
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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
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Moxifloxacin, Placebo, Efavirenz Placebo Moxifloxacin, Placebo, Efavirenz single dose as specified Moxifloxacin, Placebo, Efavirenz Moxifloxacin Moxifloxacin, Placebo, Efavirenz single dose as specified Moxifloxacin, Placebo, Efavirenz Efavirenz Moxifloxacin, Placebo, Efavirenz single dose as specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 Difference from placebo of Moxifloxacin in change from period-specific baseline in QTcF (ΔΔQTcF) following a single dose Days 1, 5 and 19 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
Trial Locations
- Locations (1)
Parexel International - Baltimore Epcu
🇺🇸Baltimore, Maryland, United States