NCT01451333

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Sep 2011

Geographic Reach
3 countries

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 5, 2011

Completed
8 months until next milestone

Study Start

First participant enrolled

September 1, 2011

Completed
1 month until next milestone

First Posted

Study publicly available on registry

October 13, 2011

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2013

Completed
Last Updated

May 13, 2013

Status Verified

May 1, 2013

Enrollment Period

1.1 years

First QC Date

January 5, 2011

Last Update Submit

May 10, 2013

Conditions

HIV Infection

Keywords

HIVEfavirenzCentral Nervous System (CNS)Lumbar punctureDose reduction

Outcome Measures

Primary Outcomes (1)

  • 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.

    24 weeks

Secondary Outcomes (8)

  • CSF EFV exposure and plasma exposure (CSF:plasma ratio) using statistical analysis

    24 weeks

  • The relationship between CSF EFV exposure and neuropsychiatric side effects using questionnaires and medical assessments

    24 weeks

  • The relationship between CSF EFV exposure and other study parameters such as race and sex.

    24 weeks

  • The number of subjects with EFV CSF exposure greater than the postulated CSF IC50 for wild type virus (0.51ng/mL)

    24 weeks

  • CSF HIV RNA measurement after 12 - 24 weeks of study therapy

    24 weeks

  • +3 more secondary outcomes

Study Arms (2)

Reduced dose Efavirenz arm

EXPERIMENTAL

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).

Drug: Efavirenz

Normal Efavirenz dose arm

ACTIVE COMPARATOR

Patient's on main study randomised to receive tenofovir (TDF) (300mg qd)/emtricitabine (FTC) (200mg qd) + EFV (600mg qd; 3 x 200mg qd)

Drug: Efavirenz

Interventions

EfavirenzDRUG

600mg qd; 3 x 200mg qd

Normal Efavirenz dose arm

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • All subjects entering into the main study protocol at participating centres will be eligible to enter this sub-study.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Medical Group Practice

Berlin, State of Berlin, 10777, Germany

Location

HIVNAT Research Collaboration

Patumwan, Bangkok, 10330, Thailand

Location

Khon Kaen University

Khon Kaen, Changwat Khon Kaen, 40002, Thailand

Location

Imperial College, St. Mary's Hospital

Clinical Trials Centre, Winston Churchil Wing, London, W2 1NY, United Kingdom

Location

Chelsea and Westminster Hospital

Hiv/gum Laboratory 5th Floor Saint Stephen Centre, London, SW10 9NH, United Kingdom

Location

MeSH Terms

Conditions

HIV Infections

Interventions

efavirenz

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Alan Winston, Dr.

    Imperial College London

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 5, 2011

First Posted

October 13, 2011

Study Start

September 1, 2011

Primary Completion

October 1, 2012

Study Completion

February 1, 2013

Last Updated

May 13, 2013

Record last verified: 2013-05

Locations

TH(2)GB(2)DE(1)