Elvucitabine/Efavirenz/Tenofovir Versus Lamivudine/Efavirenz/Tenofovir in Human Immunodeficiency Virus (HIV)-1 Infected, Treatment-naive Participants
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Elvucitabine; Lamivudine; Tenofovir; Efavirenz
Intervention description: Elvucitabine 10 mg orally daily; Lamivudine 300 mg orally daily; Tenofovir open-label 300 mg orally daily; Efavirenze open-label 600 mg orally daily
Intervention MeSH terms: Tenofovir; Lamivudine; Efavirenz; Dexelvucitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: HIV-1 treatment naive

Summary:

      Elvucitabine, a novel nucleoside analog, is being studied as a treatment for participants
      with human immunodeficiency virus (HIV)-1. This Phase 2 study will enroll 60 HIV-1-naive
      participants to assess the efficacy and safety of elvucitabine compared to lamivudine in
      combination with tenofovir and efavirenz as measured by changes in the participant's
      HIV-ribonucleic acid (RNA) level and CD4 cell count. The study treatment will be 12 weeks of
      blinded study medication followed by an additional 84 weeks of open-label treatment if the
      participant's response to treatment meets certain endpoints. The pharmacokinetics of
      elvucitabine will also be assessed during the study.
    

Eligibility criteria:

        Inclusion Criteria:

        A participant must meet the following criteria at Screening to be enrolled in this study:

          1. Are male or female. Sexually active men with partners of childbearing potential must
             agree to use an acceptable form of contraception as determined by the investigator
             (for example, oral contraceptives, double-barrier methods, hormonal injectable or
             implanted contraceptives, tubal ligation, or vasectomy) during participation in the
             study. Female participants cannot be pregnant or lactating/breast-feeding and must be
             surgically sterile, postmenopausal as defined later, or practicing an effective method
             of birth control as determined by the investigator (for example oral contraceptives,
             double-barrier methods, hormonal injectable or implanted contraceptives, tubal
             ligation, or partner with vasectomy). A woman may be considered postmenopausal if she
             is at least 50 years or older, has a history of no menses for at least 12 months, and
             has a follicle-stimulating hormone (FSH) level over the upper limit of normal for
             reproductive aged women.

          2. Are 18 through 65 years old

          3. Have documented HIV-1 infection by written prior history and clinically stable with no
             AIDS-defining events in the 3 months prior to Screening

          4. Have plasma HIV-1 RNA levels greater than or equal to 5000 copies/mL at Screening

          5. Are HIV-1 strain sensitive to elvucitabine, lamivudine, or emtricitabine as
             demonstrated by the absence of the M184V, M184I, and D237E mutations by TRUGENE HIV-1
             Genotyping Kit

          6. Are HIV-1 strain genotypically sensitive to efavirenz (negative for K103 and Y188L
             mutations) and tenofovir (negative for K65R mutation) by TRUGENE HIV-1 Genotyping Kit

          7. Have a CD4 count greater than or equal to 200 cells/mL and less than 500 cells/mL

          8. Have acceptable hematologic and chemistry parameters, including the following:

               -  Hemoglobin (Hgb) greater than or equal to 11 grams (g)/deciliter (dL)

               -  Absolute neutrophil count greater than or equal to 2000 cells/mm^3

               -  Platelets greater than or equal to 125 000/mm^3

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or
                  equal to 1.5 times the upper limit of normal

               -  Total bilirubin less than or equal to 1.5 times the upper limit of normal

               -  Creatinine within normal range

          9. Are capable of understanding and has signed the informed consent document

         10. Are able and willing to comply with protocol requirements

        Exclusion Criteria:

        Participants meeting any of the following criteria at Screening will be excluded from the
        study:

          1. Are hepatitis B surface antigen positive, and/or hepatitis B virus (HBV)
             deoxyribonucleic acid (DNA) positive

          2. Have previous therapy with agents with significant systemic myelosuppressive or
             cytotoxic potential within the 3 months prior to Screening or the expected need for
             such therapy during the study

          3. Have previous use or need for bone marrow colony-stimulating factors such as Epogen,
             Procrit, or Neupogen

          4. Have had previous antiretroviral therapy

          5. Have evidence or history of cirrhosis

          6. Have recent (within 3 months of Screening) history of alcohol abuse, physical
             dependence to any opioid, cocaine, lysergic acid diethylamide (LSD) or amphetamines,
             or history of drug addiction within the last 12 months

          7. Have inability to tolerate oral medication

          8. Are pregnant or breast-feeding if female

          9. Have any clinical condition or prior therapy that, in the investigator's opinion,
             would make the participant unsuitable for the study or unable to comply with the
             dosing requirements

         10. Have received treatment with any other investigational drug within 30 days prior to
             Screening

         11. Have current active mental illness or a history of significant mental illness (for
             example, severe depression, schizophrenia, history of suicidal ideations, or suicide
             attempts)