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

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ClinicalTrials.gov Identifier: NCT02164812
Recruitment Status : Completed
First Posted : June 17, 2014
Last Update Posted : September 7, 2015
Sponsor:
Information provided by (Responsible Party):
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.

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

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


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: A Study to Determine the Concentration-Electrocardiographic Effects of Efavirenz in Healthy Subjects Enriched for CYP2B6 Polymorphisms
Study Start Date : July 2014
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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 ]
    QTcF = QT corrected for Fridericia's formula


Secondary Outcome Measures :
  1. 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 ]
    ECG = Electrocardiogram

  2. 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 ]
  3. 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 ]
  4. Time of maximum observed plasma concentration (Tmax) of EFV [ Time Frame: Days 1, 2, 19 and 20 ]
  5. Maximum observed plasma concentration (Cmax) of EFV [ Time Frame: Days 1, 2, 19 and 20 ]
  6. Trough observed plasma concentration 24 h after a dose (C24) of EFV [ Time Frame: Days 1, 2, 19 and 20 ]
  7. Area under the concentration-time curve in one dosing interval (AUC(TAU)) of EFV [ Time Frame: Days 1, 2, 19 and 20 ]
  8. 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) ]
    Serious AE (SAE)



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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02164812


Locations
United States, Maryland
Parexel International - Baltimore Epcu
Baltimore, Maryland, United States, 21225
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02164812     History of Changes
Other Study ID Numbers: AI266-959
First Posted: June 17, 2014    Key Record Dates
Last Update Posted: September 7, 2015
Last Verified: September 2015

Additional relevant MeSH terms:
Moxifloxacin
Fluoroquinolones
Efavirenz
Norgestimate, ethinyl estradiol drug combination
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers