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Clinical Trials

MainTitle

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

This study has been completed
Sponsor
Achillion Pharmaceuticals


Information provided by (Responsible Party)
Achillion Pharmaceuticals
ClinicalTrials.gov Identifier
NCT00350272

First received: July 6, 2006
Last updated: May 16, 2016
Last Verified: May 2016
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV Infections

Drug : elvucitabine
Drug : Lamivudine
Drug : Tenofovir
Drug : Efavirenz
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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.

Further study details as provided by Achillion Pharmaceuticals:

Primary Outcome Measures

  • The Proportion of Subjects With Virologic Response for 10 mg/Day Elvucitabine in HIV-1-infected Subjects by 12 Weeks Compared With the Proportion of Subjects With Lamivudine 300 mg/Day. [ Time Frame: 12 Weeks ]
    Proportion of subjects having achieved a virologic response for elvucitabine 10 mg/day in combination with efavirenz and tenofovir in HIV-1-infected subjects over 12 weeks compared with the proportion of subjects having achieved a virologic response for lamivudine 300 mg/day in combination with efavirenz and tenofovir. Virologic response was defined as having achieved undetectable (<50 copies/mL) HIV-1 RNA levels from baseline assessment.
  • The Safety Profile of Elvucitabine. [ Time Frame: 12 Weeks ]
    Determination of the safety profile of elvucitabine as defined by the frequency, type and severity of treatment-emergent adverse events and the frequency of Grade 3 and Grade 4 laboratory abnormalities.

Enrollment: 76
Study Start Date: May 2006
Study Completion Date: April 2009
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Elvucitabine, Efavirenz,Tenofovir
Elvucitabine (blinded) 10 mg/day in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible subjects continued with an additional 84 weeks of open-label treatment (through Week 96). Subjects who experienced at least a 2 log10 decrease in HIV-1 RNA from Baseline or who had an HIV-1 RNA level of less than 400 copies/mL at Week 10 and had not experienced any Grade 3 or 4 hematological toxicity as of the Week 10 measurement were considered eligible for an additional 84 weeks of open-label treatment after Week 12.
Drug: elvucitabine

elvucitabine 10 mg orally daily

Other Name: ACH-126,443
Drug: Tenofovir

tenofovir open-label 300 mg orally daily

Other Name: viread
Drug: Efavirenz

efavirenze open-label 600 mg orally daily

Other Name: Sustiva
Active Comparator: Lamivudine,Efavirenz,Tenofovir
Lamivudine (blinded) 300 mg daily in combination with open-label efavirenz 600 mg daily and open-label tenofovir 300 mg daily, all administered orally, over 12 weeks. Eligible subjects continued with an additional 84 weeks of open-label treatment (through Week 96). Subjects who experienced at least a 2 log10 decrease in HIV-1 RNA from Baseline or who had an HIV-1 RNA level of less than 400 copies/mL at Week 10 and had not experienced any Grade 3 or 4 hematological toxicity as of the Week 10 measurement were considered eligible for an additional 84 weeks of open-label treatment after Week 12.
Drug: Lamivudine

lamivudine 300 mg orally daily

Other Name: 3TC
Drug: Tenofovir

tenofovir open-label 300 mg orally daily

Other Name: viread
Drug: Efavirenz

efavirenze open-label 600 mg orally daily

Other Name: Sustiva

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 96.
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 post treatment 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 Weeks 4, 6, 8, 12, 16, 24, 48, 72, 96, 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, 48 and 96 determination of HIV-1 phenotype at Visit 1 and at Weeks 12, 24, 48, and 96 urine and serum pregnancy tests, as well as laboratory analyses that include hematology, chemistry, and urinalysis.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 60 Years  
Sexes Eligible for Study: All  
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:
  • Are hepatitis B surface antigen positive, and/or hepatitis B virus (HBV) DNA positive
  • 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
  • Have previous use or need for bone marrow colony-stimulating factors such as Epogen, Procrit, or Neupogen
  • Have had previous antiretroviral therapy
  • Have evidence or history of cirrhosis
  • 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
  • Have inability to tolerate oral medication
  • Are pregnant or breast-feeding if female
  • 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
  • Have received treatment with any other investigational drug within 30 days prior to Screening
  • 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

    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

    Locations

    United States, Arkansas
    Health for Life Clinic
    Little Rock, Arkansas, United States, 72207
    United States, California
    Living Hope Clinical Foundation, Inc.
    Long Beach, California, United States, 90813
    Anthony Mills
    Los Angeles, California, United States, 90069
    United States, District of Columbia
    Georgetown University
    Washington, District of Columbia, United States, 20007
    United States, Florida
    Clinical Research of West Florida
    Clearwater, Florida, United States, 33765
    Associates in Research, Inc.
    Fort Myers, Florida, United States, 33901
    Steinhart Medical Associates
    Miami, Florida, United States, 33133
    University of Miami School of Medicine
    Miami, Florida, United States, 33136
    Orlando Immunology Center
    Orlando, Florida, United States, 32803
    Hillsborough County Health Department
    Tampa, Florida, United States, 33602
    Infectious Disease Research Institute, Inc.
    Tampa, Florida, United States, 33614
    Triple O Medical Services
    West Palm Beach, Florida, United States, 33401
    United States, Illinois
    Northwestern University
    Chicago, Illinois, United States, 60611
    United States, Kansas
    University of Kansas School of Medicine Wichita
    Wichita, Kansas, United States, 67214
    United States, Maryland
    Georgetown University
    Washington D.C., Maryland, United States, 20007
    United States, Massachusetts
    CRI of New England
    Boston, Massachusetts, United States, 02215
    United States, New Jersey
    Saint Michael's Medical Center
    Newark, New Jersey, United States, 07102
    United States, New York
    Beth Israel Medical Center
    New York, New York, United States, 10003
    United States, Texas
    Central Texas Clinical Research
    Austin, Texas, United States, 78705
    Nicholaos C. Bellos, MD, PA
    Dallas, Texas, United States, 75204
    Therapeutic Concepts
    Houston, Texas, United States, 77004
    Univ. of Texas Health Science Center
    Houston, Texas, United States, 77009
    Thomas Street Clinic
    Houston, Texas, United States, 77030
    Montrose Clinic
    Houston, Texas, United States, 77098
    United States, Virginia
    Hampton Roads Medical Specialist
    Hampton, Virginia, United States, 23666
    Puerto Rico
    Clinical Research Puerto Rico
    San Juan, Puerto Rico, 00909

    Sponsors and Collaborators

    Achillion Pharmaceuticals

    Investigators

    Study Director: Ron Gugliotti, MPH Achillion Pharmaceuticals
    More Information

    More Information


    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: May 16, 2016  
    Individual Participant Data    
    Plan to Share IPD: Yes  

    Keywords provided by Achillion Pharmaceuticals:

    HIV-1 treatment naive

    Additional relevant MeSH terms:
    HIV Infections
    Tenofovir
    Lamivudine
    Efavirenz
    Zalcitabine

    ClinicalTrials.gov processed this data on October 16, 2017
    This information is provided by ClinicalTrials.gov.