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The Efavirenz (EFV) Central Nervous System Exposure Sub-study of Encore1 (ENCORE1-CNS)

This study has been completed.
Sponsor:
Collaborator:
Imperial College London
Information provided by (Responsible Party):
Kirby Institute
ClinicalTrials.gov Identifier:
NCT01451333
First received: January 5, 2011
Last updated: May 10, 2013
Last verified: May 2013
History of Changes

January 5, 2011
May 10, 2013
September 2011
October 2012   (final data collection date for primary outcome measure)
comparison of mean CSF concentration of EFV from both doses after week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
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.
Describe the CSF exposure of EFV from both doses [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
To describe the CSF exposure of EFV when dosed at 400mg and 600mg daily. Efavirenz plasma and CSF concentrations will be determined and CSF:plasma ratios expressed as a percentage. Associations between plasma and CSF concentrations and relationship to study clinical parameters will be undertaken.
Complete list of historical versions of study NCT01451333 on ClinicalTrials.gov Archive Site
  • CSF EFV exposure and plasma exposure (CSF:plasma ratio) using statistical analysis [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • The relationship between CSF EFV exposure and other study parameters such as race and sex. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • CSF HIV RNA measurement after 12 - 24 weeks of study therapy [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Relationship between plasma HIV RNA and CSF HIV RNA [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • CSF biomarker analysis after 12 - 24 weeks of study therapy [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • comparison between magnetic resonance (MR) spectroscopy findings and CSF HIV RNA and EFV concentration [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • CSF EFV exposure and plasma exposure (CSF:plasma ratio), both for protein bound and free plasma EFV exposure [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    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 (as assessed in main study protocol) [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • The relationship between CSF EFV exposure and other study parameters (such as race, sex, any allowed concomitant medication) [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • CSF HIV RNA measurement after 12 - 24 weeks of study therapy [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Relationship between plasma HIV RNA and CSF HIV RNA [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • CSF biomarker analysis after 12 - 24 weeks of study therapy [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • The relationship between magnetic resonance (MR) spectroscopy findings and CSF HIV RNA and EFV concentration [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
The Efavirenz (EFV) Central Nervous System Exposure Sub-study of Encore1
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

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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
HIV Infection
  • Drug: Efavirenz
    600mg qd; 3 x 200mg qd
  • Drug: Efavirenz
    400mg qd; 2 x 200mg
  • Experimental: Reduced dose Efavirenz arm
    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).
    Intervention: Drug: Efavirenz
  • Active Comparator: Normal Efavirenz dose arm
    Patient's on main study randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd)
    Intervention: Drug: Efavirenz
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
February 2013
October 2012   (final data collection date for primary outcome measure)

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
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany,   Thailand,   United Kingdom
 
NCT01451333
NCHECR-ENCORE1-CNS
Yes
Kirby Institute
Kirby Institute
Imperial College London
Principal Investigator: Alan Winston, Dr. Imperial College London
Kirby Institute
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP