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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT02164812
First received: June 13, 2014
Last updated: July 9, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
HIV/AIDS
Drug: Moxifloxacin
Drug: Placebo
Drug: Efavirenz
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Study to Determine the Concentration-Electrocardiographic Effects of Efavirenz in Healthy Subjects Enriched for CYP2B6 Polymorphisms

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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) [ Time Frame: Days 1, 2, 5, 6, 19 and 20 ] [ Designated as safety issue: Yes ]
    QTcF = QT corrected for Fridericia's formula


Secondary Outcome Measures:
  • 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 [ Time Frame: Days 1, 5 and 19 ] [ Designated as safety issue: Yes ]
    ECG = Electrocardiogram

  • Difference from placebo of Moxifloxacin in change from period-specific baseline in QTcF (ΔΔQTcF) following a single dose [ Time Frame: Days 1, 5 and 19 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Days 1, 5 and 19 ] [ Designated as safety issue: Yes ]
  • Time of maximum observed plasma concentration (Tmax) of EFV [ Time Frame: Days 1, 2, 19 and 20 ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration (Cmax) of EFV [ Time Frame: Days 1, 2, 19 and 20 ] [ Designated as safety issue: No ]
  • Trough observed plasma concentration 24 h after a dose (C24) of EFV [ Time Frame: Days 1, 2, 19 and 20 ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve in one dosing interval (AUC(TAU)) of EFV [ Time Frame: Days 1, 2, 19 and 20 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Up to 30 days after discontinuation of dose (approximately 52 days) ] [ Designated as safety issue: Yes ]
    Serious AE (SAE)


Estimated Enrollment: 60
Study Start Date: July 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Moxifloxacin, Placebo, Efavirenz
Moxifloxacin, Placebo, Efavirenz single dose as specified
Drug: Moxifloxacin
Other Name: Avelox®
Drug: Placebo Drug: Efavirenz
Other Names:
  • Sustiva®
  • BMS-561525

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

  Eligibility

Ages Eligible for Study:   18 Years to 49 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02164812

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

Locations
United States, Maryland
Parexel International - Baltimore Epcu Recruiting
Baltimore, Maryland, United States, 21225
Contact: Azra Hussaini, Site 0001    410-350-7979      
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02164812     History of Changes
Other Study ID Numbers: AI266-959
Study First Received: June 13, 2014
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Efavirenz
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014