Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of CYP2B6 Genetic Polymorphisms on Efavirenz Pharmacokinetics

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00668395
Recruitment Status : Completed
First Posted : April 29, 2008
Results First Posted : September 26, 2014
Last Update Posted : September 26, 2014
Sponsor:
Information provided by (Responsible Party):
Indiana University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition HIV
Intervention Drug: Efavirenz
Enrollment 73
Recruitment Details Healthy subjects from self -referrals, campus fliers, Indiana University's Clinical Trials Webpage, community bulletin boards and newspaper were enrolled. All subjects were studied at the Indiana Clinical Research Center. Recruitment was completed within 3 years (8/20/07 to 4/15/10).
Pre-assignment Details The study was initially designed to enroll subjects with prespecified CYP2B6 genotype (*1/*1, *1/*6, and *6/*6; n=20 each), but it was later modified in which subjects were enrolled without pregenotype information and genotype was performed post-hoc.
Arm/Group Title CYP2B6*1/*1 Genotype Group CYP2B6*1/*6 Genotype Group CYP2B6*6/*6 Genotype Group
Hide Arm/Group Description
  1. Efavirenz clearance following a single 600 mg oral dose of efavirenz and after multiple doses of efavirenz (600 mg/day orally for 17 days) was analyzed in normal metabolizer of CYP2B6 (CYP2B6*1/*1 genotype), intermediate metabolizer (CYP2B6*1/*6 genotype) and slow metabolizer (CYP2B6*6/*6).

    During the study, the design was slightly modified to sequentially enroll instead of allocation based on specific genotype, and genotype effect was analyzed post-hoc.

  2. The activities of CYP1A2, CYP2C9, CYP2C19, CYP3A were determined in all subjects (without regard to CYP2B6 genotype) using the metabolism of isoform selective probe substrates during the single dose (600 mg efavirenz orally) and after intake of multiple doses of efavirenz (600 mg/day efavirenz orally for 17 days) to assess efavirenz mediated drug interactions.
  1. Efavirenz clearance following a single 600 mg oral dose of efavirenz and after multiple doses of efavirenz (600 mg/day orally for 17 days) was analyzed in normal metabolizer of CYP2B6 (CYP2B6*1/*1 genotype), intermediate metabolizer (CYP2B6*1/*6 genotype) and slow metabolizer (CYP2B6*6/*6).

    During the study, the design was slightly modified to sequentially enroll instead of allocation based on specific genotype, and genotype effect was analyzed post-hoc.

  2. The activities of CYP1A2, CYP2C9, CYP2C19, CYP3A were determined in all subjects (without regard to CYP2B6 genotype) using the metabolism of isoform selective probe substrates during the single dose (600 mg efavirenz orally) and after intake of multiple doses of efavirenz (600 mg/day efavirenz orally for 17 days) to assess efavirenz mediated drug interactions.
  1. Efavirenz clearance following a single 600 mg oral dose of efavirenz and after multiple doses of efavirenz (600 mg/day orally for 17 days) was analyzed in normal metabolizer of CYP2B6 (CYP2B6*1/*1 genotype), intermediate metabolizer (CYP2B6*1/*6 genotype) and slow metabolizer (CYP2B6*6/*6).

    During the study, the design was slightly modified to sequentially enroll instead of allocation based on specific genotype, and genotype effect was analyzed post-hoc.

  2. The activities of CYP1A2, CYP2C9, CYP2C19, CYP3A were determined in all subjects (without regard to CYP2B6 genotype) using the metabolism of isoform selective probe substrates during the single dose (600 mg efavirenz orally) and after intake of multiple doses of efavirenz (600 mg/day efavirenz orally for 17 days) to assess efavirenz mediated drug interactions.
Period Title: Overall Study
Started 45 22 6
Completed 39 16 5
Not Completed 6 6 1
Reason Not Completed
Withdrawal by Subject             4             4             1
Adverse Event             1             1             0
Physician Decision             1             1             0
Arm/Group Title CYP2B6*1/*1 CYP2B6*1/*6 CYP2B6*6/*6 Total
Hide Arm/Group Description Normal metabolizer Intermediate metabolizer Slow metabolizer Total of all reporting groups
Overall Number of Baseline Participants 45 22 6 73
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 45 participants 22 participants 6 participants 73 participants
28.3  (10.2) 29.5  (9.9) 23.2  (3.9) 28.2  (9.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 22 participants 6 participants 73 participants
Female
17
  37.8%
6
  27.3%
4
  66.7%
27
  37.0%
Male
28
  62.2%
16
  72.7%
2
  33.3%
46
  63.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 22 participants 6 participants 73 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
2
   9.1%
0
   0.0%
2
   2.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
9
  20.0%
4
  18.2%
3
  50.0%
16
  21.9%
White
35
  77.8%
14
  63.6%
3
  50.0%
52
  71.2%
More than one race
1
   2.2%
2
   9.1%
0
   0.0%
3
   4.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
BMI   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 45 participants 22 participants 6 participants 73 participants
23.9  (3.5) 25.4  (4.1) 22.0  (3.0) 24.2  (3.7)
[1]
Measure Description: A number of demographic parameters were collected at screening and during the completion of the study (exit).
Body weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 45 participants 22 participants 6 participants 73 participants
73.6  (13) 77.2  (14.1) 65  (5.3) 74  (13.4)
1.Primary Outcome
Title Effect of CYP2B6 Genotype on Efavirenz Clearance
Hide Description Efavirenz clearance is a measure of rate of elimination of the drug from the body. We used this measure to evaluate differences in rate of elimination of efavirenz at a single dose and after multiple dosing within three CYP2B6 genotypes (CYP2B6*1/*1, *1/*6 and CYP2B6*6/*6). Efavirenz clearance was measured in normal metabolizer of CYP2B6 (CYP2B6*1/*1 genotype), intermediate metabolizer (CYP2B6*1/*6) and slow metabolizer (CYP2B6*6/*6) at a single 600 mg oral dose of efavirenz and then after multiple dosing (autoinduction), i.e., the administration of efavirenz (600 mg/day) for 17 days. Single and multiple dose efavirenz clearance was measured and compared to determine the extent of autoinduction within this genotype group.
Time Frame Efavirenz clearance at single dose and multiple dose stratified by CYP2B6 genotypes
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CYP2B6*1/*1 CYP2B6*1/*6 CYP2B6*6/*6
Hide Arm/Group Description:
Normal metabolizer
Intermediate metabolizer
Slow metabolizer
Overall Number of Participants Analyzed 38 17 5
Mean (Standard Deviation)
Unit of Measure: ml/h/kg
Single efavirenz dose 93.35  (21.74) 76.08  (21.59) 51.03  (12.06)
Multiple efavirenz dose 50.05  (36.04) 119.90  (39.15) 80.12  (38.12)
Time Frame Adverse events were collected during the study period which was approximately 30 days. I some case, follow-up assessment was carried out up to 2 months after completion of the study and subject was discharged from the study.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title CYP2B6*1/*1 CYP2B6*1/*6 CYP2B6*6/*6
Hide Arm/Group Description Normal metabolizer Intermediate metabolizer Slow metabolizer
All-Cause Mortality
CYP2B6*1/*1 CYP2B6*1/*6 CYP2B6*6/*6
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
CYP2B6*1/*1 CYP2B6*1/*6 CYP2B6*6/*6
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/45 (0.00%)   0/22 (0.00%)   0/6 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
CYP2B6*1/*1 CYP2B6*1/*6 CYP2B6*6/*6
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/45 (0.00%)   0/22 (0.00%)   0/6 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Zeruesenay Desta, PhD
Organization: Indiana University School of Medicine
Phone: 317-274-2823
EMail: zdesta@iu.edu
Layout table for additonal information
Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00668395    
Other Study ID Numbers: 1010002585 | 0704-14
First Submitted: November 27, 2007
First Posted: April 29, 2008
Results First Submitted: April 10, 2013
Results First Posted: September 26, 2014
Last Update Posted: September 26, 2014