The Efavirenz (EFV) Central Nervous System Exposure Sub-study of Encore1 (ENCORE1-CNS)
Primary Purpose
HIV Infection
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Efavirenz
Efavirenz
Sponsored by

About this trial
This is an interventional treatment trial for HIV Infection focused on measuring HIV, Efavirenz, Central Nervous System (CNS), Lumbar puncture, Dose reduction
Eligibility Criteria
Inclusion Criteria:
- All subjects entering into the main study protocol at participating centres will be eligible to enter this sub-study.
Exclusion Criteria:
- Existing neurological disease which in the opinion of the investigator would be a contra-indication to lumbar puncture examination
- CNS opportunistic infections in the past 12 weeks of randomisation
- Bacterial or viral meningitis in the past 12 weeks of randomisation
- Head injury requiring medical assessment in the past 12 weeks of randomisation
Sites / Locations
- Medical Group Practice
- HIVNAT Research Collaboration
- Khon Kaen University
- Imperial College, St. Mary's Hospital
- Chelsea and Westminster Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Reduced dose Efavirenz arm
Normal Efavirenz dose arm
Arm Description
Patient's on main study that was randomised to receive TDF (300mg qd)/FTC (200mg qd) + EFV (400mg qd; 2 x 200mg + 1 x 200mg placebo qd).
Patient's on main study randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd)
Outcomes
Primary Outcome Measures
comparison of mean CSF concentration of EFV from both doses after week 24.
measure the CSF exposure of EFV when dosed at 400mg and 600mg daily. Efavirenz plasma and CSF concentrations will be analysed and CSF:plasma ratios will be compared. Associations between plasma and CSF concentrations and relationship to study clinical parameters will be assessed.
Secondary Outcome Measures
CSF EFV exposure and plasma exposure (CSF:plasma ratio) using statistical analysis
The relationship between CSF EFV exposure and plasma exposure (CSF:plasma ratio), both for protein bound and free plasma EFV exposure.
The relationship between CSF EFV exposure and neuropsychiatric side effects using questionnaires and medical assessments
The relationship between CSF EFV exposure and other study parameters such as race and sex.
The number of subjects with EFV CSF exposure greater than the postulated CSF IC50 for wild type virus (0.51ng/mL)
CSF HIV RNA measurement after 12 - 24 weeks of study therapy
Relationship between plasma HIV RNA and CSF HIV RNA
CSF biomarker analysis after 12 - 24 weeks of study therapy
comparison between magnetic resonance (MR) spectroscopy findings and CSF HIV RNA and EFV concentration
Full Information
NCT ID
NCT01451333
First Posted
January 5, 2011
Last Updated
May 10, 2013
Sponsor
Kirby Institute
Collaborators
Imperial College London
1. Study Identification
Unique Protocol Identification Number
NCT01451333
Brief Title
The Efavirenz (EFV) Central Nervous System Exposure Sub-study of Encore1
Acronym
ENCORE1-CNS
Official Title
The EFV Central Nervous System Exposure Sub-study of Encore1: A Randomised, Double-blind, Placebo-controlled, Clinical Trial to Compare the Safety and Efficacy of Reduced Dose Efavirenz (EFV) With Standard Dose EFV Plus Two Nucleotide Reverse Transcriptase Inhibitors (N(t)RTI) in Antiretroviral-naïve HIV-infected Individuals Over 96 Weeks
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
September 2011 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kirby Institute
Collaborators
Imperial College London
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Persistent HIV infection in the central nervous system (CNS) compartment may put subjects at risk of developing HIV-related brain disease. Important factors associated with the development of HIV-related brain disease include therapeutic concentrations of antiretroviral drugs in the CNS. Conflicting evidence regarding the CNS exposure of the antiretroviral drug used for the encore1 study, efavirenz (EFV) have been described in related studies. There were recent study of two small series assessment of EFV exposure in the cerebral spinal fluid (CSF); one group reported small detectable EFV concentrations, while another observed undetectable EFV exposure in the CSF. Also, in a larger reported series comprising of 80 subjects on EFV-containing antiretroviral therapy, a CSF to plasma concentration suggested that there is limited movement of EFV out of the CSF. In HIV-1 infected subjects at steady state, EFV plasma level parameters are dose proportional following 200mg, 400mg, and 600mg daily doses. The CNS exposure of EFV at different daily dosing has not been described.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection
Keywords
HIV, Efavirenz, Central Nervous System (CNS), Lumbar puncture, Dose reduction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Reduced dose Efavirenz arm
Arm Type
Experimental
Arm Description
Patient's on main study that was randomised to receive TDF (300mg qd)/FTC (200mg qd) + EFV (400mg qd; 2 x 200mg + 1 x 200mg placebo qd).
Arm Title
Normal Efavirenz dose arm
Arm Type
Active Comparator
Arm Description
Patient's on main study randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd)
Intervention Type
Drug
Intervention Name(s)
Efavirenz
Intervention Description
600mg qd; 3 x 200mg qd
Intervention Type
Drug
Intervention Name(s)
Efavirenz
Intervention Description
400mg qd; 2 x 200mg
Primary Outcome Measure Information:
Title
comparison of mean CSF concentration of EFV from both doses after week 24.
Description
measure the CSF exposure of EFV when dosed at 400mg and 600mg daily. Efavirenz plasma and CSF concentrations will be analysed and CSF:plasma ratios will be compared. Associations between plasma and CSF concentrations and relationship to study clinical parameters will be assessed.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
CSF EFV exposure and plasma exposure (CSF:plasma ratio) using statistical analysis
Description
The relationship between CSF EFV exposure and plasma exposure (CSF:plasma ratio), both for protein bound and free plasma EFV exposure.
Time Frame
24 weeks
Title
The relationship between CSF EFV exposure and neuropsychiatric side effects using questionnaires and medical assessments
Time Frame
24 weeks
Title
The relationship between CSF EFV exposure and other study parameters such as race and sex.
Time Frame
24 weeks
Title
The number of subjects with EFV CSF exposure greater than the postulated CSF IC50 for wild type virus (0.51ng/mL)
Time Frame
24 weeks
Title
CSF HIV RNA measurement after 12 - 24 weeks of study therapy
Time Frame
24 weeks
Title
Relationship between plasma HIV RNA and CSF HIV RNA
Time Frame
24 weeks
Title
CSF biomarker analysis after 12 - 24 weeks of study therapy
Time Frame
24 weeks
Title
comparison between magnetic resonance (MR) spectroscopy findings and CSF HIV RNA and EFV concentration
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All subjects entering into the main study protocol at participating centres will be eligible to enter this sub-study.
Exclusion Criteria:
Existing neurological disease which in the opinion of the investigator would be a contra-indication to lumbar puncture examination
CNS opportunistic infections in the past 12 weeks of randomisation
Bacterial or viral meningitis in the past 12 weeks of randomisation
Head injury requiring medical assessment in the past 12 weeks of randomisation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan Winston, Dr.
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical Group Practice
City
Berlin
ZIP/Postal Code
10777
Country
Germany
Facility Name
HIVNAT Research Collaboration
City
Patumwan
State/Province
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Khon Kaen University
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Imperial College, St. Mary's Hospital
City
Clinical Trials Centre, Winston Churchil Wing
State/Province
London
ZIP/Postal Code
W2 1NY
Country
United Kingdom
Facility Name
Chelsea and Westminster Hospital
City
HIV/GUM laboratory 5th floor St. Stephen Centre
State/Province
London
ZIP/Postal Code
SW10 9NH
Country
United Kingdom
12. IPD Sharing Statement
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The Efavirenz (EFV) Central Nervous System Exposure Sub-study of Encore1
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