Comparison of Elvucitabine/Efavirenz/Tenofovir Versus Lamivudine/Efavirenz/Tenofovir in HIV-1 Infected, Treatment Naive Subjects
Elvucitabine is a novel nucleoside analog that is being studied as a teatment for patients infected with HIV-1. This Phase II study will enroll 60 HIV-1 naive subjects to assess the efficacy and safety of elvucitabine compared to lamivudine in combination with tenofovir and efavirenz measured by changes in the patient's HIV-RNA level and CD4 cell count. The study teatment will be 12 weeks of blinded study medication followed by an additional 36 weeks of open label treatment if the patient's response to teatment meets certain endpoints. Also there will be assessment of the pharmacokinetics of elvucitabine during the study.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Randomized, Blinded, 12-week Comparison of Elvucitabine/Efavirenz/Tenofovir Versus Lamivudine/Efavirenz/Tenofovir in HIV-1 Infected, Treatment Naive Subjects. There is a 36 Week, Open Label, Extension Phase for Eligible Subjects.|
- Primary: [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Determination of the proportion of subjects having achieved a virologic response for 10 mg/day elvucitabine in combination with efavirenz and tenofovir in human immunodeficiency virus type 1 (HIV-1)-infected subjects by 12 weeks compared with the propor [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
- Determination of the safety profile of elvucitabine. [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]
- Secondary: [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
- Determination of the pharmacokinetics (PK) of 10-mg/day elvucitabine over 12 weeks as measured by concentrations of elvucitabine in plasma and of elvucitabine triphosphate in peripheral blood mononuclear cells [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
- Determination of the efficacy of the study treatment regimen compared with the standard regimen, as measured by the change in HIV 1¬ RNA and helper T cell (CD4) count. [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
|Study Start Date:||April 2006|
|Study Completion Date:||July 2009|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
|Active Comparator: Elvucitabine, Efavirenz,Tenofovir||Drug: elvucitabine Drug: Tenofovir Drug: Efavirenz|
|Active Comparator: Lamivudine,Efavirenz,Tenofovir||Drug: Lamivudine Drug: Tenofovir Drug: Efavirenz|
Sixty HIV-1-infected, clinically stable, treatment-naïve adults with no acquired immunodeficiency syndrome (AIDS)-defining events during the 3 months prior to screening will be randomly assigned to 1 of 2 treatment groups. Subject plasma HIV-1 RNA levels must be greater than or equal to 5000 copies/mL and CD4 cell counts must be greater than 200 cells/mL and less than 500 cells/mL at Screening. Subjects must be sensitive to elvucitabine, lamivudine, and emtricitabine as demonstrated by the absence of the M184V, M184I, and D237E mutations by TRUGENE HIV-1 Genotyping Kit. Subjects must be genotypically sensitive to efavirenz (negative for K103 or Y188L mutations) and tenofovir (negative for K65R mutation) as demonstrated by TRUGENE HIV-1 Genotyping Kit. They must have acceptable hematologic and chemistry parameters.
Subjects whose HIV-1 RNA levels have decreased at least 2 logs or to below 400 copies/mL by Week 10 may be considered eligible to enter the extension phase of up to 36 weeks of additional treatment. Subjects in the extension phase will be evaluated at Weeks 14, 16, and every 4 weeks until week 48.
Once all subjects have completed 12 weeks of treatment, and the data are available for all visits through Week 12, the database will be locked and the treatment assignments will be unblinded. Any subject who has had less than 48 weeks of treatment will be allowed to continue on the same treatment as initially assigned on an open-label basis through 48 weeks. All subjects will have 2 posttreatment follow-up visits, at 1 and 4 weeks after the end of treatment. Concentrations of elvucitabine in plasma will be measured on Day 1, at Week 4, Week 6, Week 8, Week 12, Week 16, Week 24, and at Follow-up
Efficacy will be assessed by measuring plasma HIV-1 RNA levels and CD4 counts at each study visit.
Safety evaluation will include vital signs, physical examinations, electrocardiograms, assessments of adverse events (AEs), measurement of plasma HIV-1 RNA levels and CD4 counts, determination of HIV-1 genotype at Screening, and at Weeks 12, 24, and 48 determination of HIV-1 phenotype at Visit 1 and at Weeks 12, 24, and 48 urine and serum pregnancy tests, as well as laboratory analyses that include hematology, chemistry, and urinalysis.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00350272
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|Study Director:||Ron Gugliotti, MPH||Achillion Pharmaceuticals|