Study to Determine the Effect of Efavirenz on the ECG QTcF Interval in Healthy Subjects

HIV/AIDS Clinical Trial

Official title:

A Study to Determine the Concentration-Electrocardiographic Effects of Efavirenz in Healthy Subjects Enriched for CYP2B6 Polymorphisms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02164812
• Other study ID #: AI266-959
• Status: Completed
• Phase: Phase 1
• First received: June 13, 2014
• Last updated: September 3, 2015
• Start date: July 2014
• Est. completion date: August 2015

Study information

• Verified date: September 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 49 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• HIV/AIDS

Intervention

Drug:
• Moxifloxacin

• Placebo

• Efavirenz

Locations

Country	Name	City	State
United States	Parexel International - Baltimore Epcu	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 (??QTcF)	QTcF = QT corrected for Fridericia's formula	Days 1, 2, 5, 6, 19 and 20	Yes
Secondary	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	ECG = Electrocardiogram	Days 1, 5 and 19	Yes
Secondary	Difference from placebo of Moxifloxacin in change from period-specific baseline in QTcF (??QTcF) following a single dose		Days 1, 5 and 19	No
Secondary	Number and percent of subjects having a maximum QTcF, HR, PR, and QRS outside of pre-specified categories and those having a maximum ?QTcF outside of pre-specified categories		Days 1, 5 and 19	Yes
Secondary	Time of maximum observed plasma concentration (Tmax) of EFV		Days 1, 2, 19 and 20	No
Secondary	Maximum observed plasma concentration (Cmax) of EFV		Days 1, 2, 19 and 20	No
Secondary	Trough observed plasma concentration 24 h after a dose (C24) of EFV		Days 1, 2, 19 and 20	No
Secondary	Area under the concentration-time curve in one dosing interval (AUC(TAU)) of EFV		Days 1, 2, 19 and 20	No
Secondary	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	Serious AE (SAE)	Up to 30 days after discontinuation of dose (approximately 52 days)	Yes

External Links

•   BMS clinical trial educational resource
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