Comparison of Elvucitabine/Efavirenz/Tenofovir Versus Lamivudine/Efavirenz/Tenofovir in HIV-1 Infected, Treatment Naive Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Achillion Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00350272
First received: July 6, 2006
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: elvucitabine
Drug: Lamivudine
Drug: Tenofovir
Drug: Efavirenz
Phase 2

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Achillion Pharmaceuticals:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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 ]

Enrollment: 76
Study Start Date: April 2006
Study Completion Date: July 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Elvucitabine, Efavirenz,Tenofovir Drug: elvucitabine Drug: Tenofovir Drug: Efavirenz
Active Comparator: Lamivudine,Efavirenz,Tenofovir Drug: Lamivudine Drug: Tenofovir Drug: Efavirenz

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00350272

  Show 26 Study Locations
Sponsors and Collaborators
Achillion Pharmaceuticals
Investigators
Study Director: Ron Gugliotti, MPH Achillion Pharmaceuticals
  More Information

No publications provided

Responsible Party: Achillion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00350272     History of Changes
Other Study ID Numbers: ACH443-015
Study First Received: July 6, 2006
Last Updated: April 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Achillion Pharmaceuticals:
HIV-1 treatment naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Efavirenz
Lamivudine
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014