Elvucitabine/Efavirenz/Tenofovir vs. Lamivudine/Efavirenz/Tenofovir in HIV-1 Infected, Treatment Naive Subjects

• Status: Completed
• Trial end date: 2009-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Elvucitabine is a novel nucleoside analog that is being studied as a treatment 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 treatment will be 12 weeks of blinded study medication followed by an additional 84 weeks of open label treatment if the patient's response to treatment meets certain endpoints. Also there will be assessment of the pharmacokinetics of elvucitabine during the study.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Achillion Pharmaceuticals; Alexion Pharmaceuticals
• Treatments: Dexelvucitabine; Efavirenz; Lamivudine; Tenofovir; Zalcitabine

Criteria

Inclusion Criteria:

A subject 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 (eg, oral contraceptives, double-barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or vasectomy) during participation in the study. Female subjects 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 (eg, 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 an 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, 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 11g/dL

• Absolute neutrophil count greater than or equal to 2000 cells/mm3

• Platelets greater than or equal to 125 000/mm3

• 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:

Subjects 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) 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, 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 subject 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 (eg, severe depression, schizophrenia, history of suicidal ideations, or suicide attempts).