Ignite Creation Date:
2025-12-25 @ 3:00 AM
Ignite Modification Date:
2025-12-31 @ 11:05 AM
Study NCT ID:
NCT01451333
Status:
COMPLETED
Last Update Posted:
2013-05-13
First Post:
2011-01-05
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Efavirenz (EFV) Central Nervous System Exposure Sub-study of Encore1
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015658', 'term': 'HIV Infections'}], 'ancestors': [{'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D003141', 'term': 'Communicable Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D015229', 'term': 'Sexually Transmitted Diseases, Viral'}, {'id': 'D012749', 'term': 'Sexually Transmitted Diseases'}, {'id': 'D016180', 'term': 'Lentivirus Infections'}, {'id': 'D012192', 'term': 'Retroviridae Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007153', 'term': 'Immunologic Deficiency Syndromes'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C098320', 'term': 'efavirenz'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 32}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-05', 'completionDateStruct': {'date': '2013-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2013-05-10', 'studyFirstSubmitDate': '2011-01-05', 'studyFirstSubmitQcDate': '2011-10-12', 'lastUpdatePostDateStruct': {'date': '2013-05-13', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2011-10-13', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'comparison of mean CSF concentration of EFV from both doses after week 24.', 'timeFrame': '24 weeks', '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.'}], 'secondaryOutcomes': [{'measure': 'CSF EFV exposure and plasma exposure (CSF:plasma ratio) using statistical analysis', 'timeFrame': '24 weeks', 'description': 'The relationship between CSF EFV exposure and plasma exposure (CSF:plasma ratio), both for protein bound and free plasma EFV exposure.'}, {'measure': 'The relationship between CSF EFV exposure and neuropsychiatric side effects using questionnaires and medical assessments', 'timeFrame': '24 weeks'}, {'measure': 'The relationship between CSF EFV exposure and other study parameters such as race and sex.', 'timeFrame': '24 weeks'}, {'measure': 'The number of subjects with EFV CSF exposure greater than the postulated CSF IC50 for wild type virus (0.51ng/mL)', 'timeFrame': '24 weeks'}, {'measure': 'CSF HIV RNA measurement after 12 - 24 weeks of study therapy', 'timeFrame': '24 weeks'}, {'measure': 'Relationship between plasma HIV RNA and CSF HIV RNA', 'timeFrame': '24 weeks'}, {'measure': 'CSF biomarker analysis after 12 - 24 weeks of study therapy', 'timeFrame': '24 weeks'}, {'measure': 'comparison between magnetic resonance (MR) spectroscopy findings and CSF HIV RNA and EFV concentration', 'timeFrame': '24 weeks'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['HIV', 'Efavirenz', 'Central Nervous System (CNS)', 'Lumbar puncture', 'Dose reduction'], 'conditions': ['HIV Infection']}, 'descriptionModule': {'briefSummary': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '16 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* All subjects entering into the main study protocol at participating centres will be eligible to enter this sub-study.\n\nExclusion Criteria:\n\n* Existing neurological disease which in the opinion of the investigator would be a contra-indication to lumbar puncture examination\n* CNS opportunistic infections in the past 12 weeks of randomisation\n* Bacterial or viral meningitis in the past 12 weeks of randomisation\n* Head injury requiring medical assessment in the past 12 weeks of randomisation'}, 'identificationModule': {'nctId': 'NCT01451333', 'acronym': 'ENCORE1-CNS', 'briefTitle': 'The Efavirenz (EFV) Central Nervous System Exposure Sub-study of Encore1', 'organization': {'class': 'OTHER_GOV', 'fullName': 'Kirby Institute'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'NCHECR-ENCORE1-CNS'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Reduced dose Efavirenz 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).", 'interventionNames': ['Drug: Efavirenz']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Normal Efavirenz dose 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)", 'interventionNames': ['Drug: Efavirenz']}], 'interventions': [{'name': 'Efavirenz', 'type': 'DRUG', 'description': '600mg qd; 3 x 200mg qd', 'armGroupLabels': ['Normal Efavirenz dose arm']}, {'name': 'Efavirenz', 'type': 'DRUG', 'description': '400mg qd; 2 x 200mg', 'armGroupLabels': ['Reduced dose Efavirenz arm']}]}, 'contactsLocationsModule': {'locations': [{'zip': '10777', 'city': 'Berlin', 'state': 'State of Berlin', 'country': 'Germany', 'facility': 'Medical Group Practice', 'geoPoint': {'lat': 52.52437, 'lon': 13.41053}}, {'zip': '10330', 'city': 'Patumwan', 'state': 'Bangkok', 'country': 'Thailand', 'facility': 'HIVNAT Research Collaboration'}, {'zip': '40002', 'city': 'Khon Kaen', 'state': 'Changwat Khon Kaen', 'country': 'Thailand', 'facility': 'Khon Kaen University', 'geoPoint': {'lat': 16.44671, 'lon': 102.833}}, {'zip': 'W2 1NY', 'city': 'Clinical Trials Centre, Winston Churchil Wing', 'state': 'London', 'country': 'United Kingdom', 'facility': "Imperial College, St. Mary's Hospital"}, {'zip': 'SW10 9NH', 'city': 'Hiv/gum Laboratory 5th Floor Saint Stephen Centre', 'state': 'London', 'country': 'United Kingdom', 'facility': 'Chelsea and Westminster Hospital'}], 'overallOfficials': [{'name': 'Alan Winston, Dr.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Imperial College London'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Kirby Institute', 'class': 'OTHER_GOV'}, 'collaborators': [{'name': 'Imperial College London', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}