Study of Once Daily Elvucitabine Versus Lamivudine in Subjects With a Documented M184V Mutation (Resistance)

This study has been completed.
Sponsor:
Information provided by:
Achillion Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00312039
First received: April 5, 2006
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

HIV-1 infected patients receiving long-term therapy with lamivudine or emtricitabine (nucleoside reverse transcriptase inhibitors [NRTIs]) are at risk for the development of a mutation at position M184 on the HIV reverse transcriptase gene. This mutation confers resistance to both drugs (> 100 fold increase in IC50).

In-vitro studies with elvucitabine have shown that HIV-1 isolates with the M184V mutation show only a 10-fold increase in IC50 as compared to wild type HIV-1. Achillion Pharmaceutical's intention is to demonstrate that 10 mg of elvucitabine, administered once per day for 14 days with continued background anti-HIV-1 medications, will demonstrate a fall in HIV-1 RNA plasma levels, as compared to baseline. The data from this study will guide dosing in future long-term studies in HIV-1 infected patients with the M184V mutation.


Condition Intervention Phase
HIV Infections
Drug: elvucitabine
Drug: Lamivudine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 14 Day Randomized, Double Blind, Study of Once Daily Elvucitabine Versus Lamivudine in Subjects With a Documented M184V Mutation

Resource links provided by NLM:


Further study details as provided by Achillion Pharmaceuticals:

Primary Outcome Measures:
  • Reduction in viral load [ Time Frame: 14 days ]

Secondary Outcome Measures:
  • safety [ Time Frame: 14 days ]

Estimated Enrollment: 20
Study Start Date: March 2006
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: elvucitabine
Elvucitabine 10 mg QD for 14days
Active Comparator: B Drug: Lamivudine
Lamivudine 300 mg QD for 14 days

Detailed Description:

Protocol Title: A 14-Day, Randomized, Double-Blind, Comparative Viral Kinetic Study of Elvucitabine Versus Lamivudine Administered Once Daily to HIV-1 Infected Subjects With a Documented M184V Variant Protocol Number: ACH443-014A Clinical Phase: 2a Primary Objectives: • To assess the viral kinetics of 10 mg of elvucitabine administered once daily (QD) for 14 days in combination with background antiretroviral therapy in HIV-1-infected subjects with a documented M184V variant

  • To demonstrate the antiviral activity of 10 mg of elvucitabine administered QD for 14 days in combination with background antiretroviral therapy as compared with lamivudine in combination with background antiretroviral therapy in HIV-1 infected subjects with a documented M184V variant
  • To assess the safety of elvucitabine therapy in HIV-1 infected subjects with a documented M184V variant Number of Subjects: 20 Number of Study Centers: Multi-center study Study Population: HIV-1 infected subjects who are presently failing an antiretroviral therapy regimen containing lamivudine or emtricitabine, genotypically demonstrate a MI84V variant, and have an HIV RNA plasma level ≥ 2,000 and ≤ 150,000 copies/mL. Study Design: HIV-1 infected subjects, with a documented M184V variant, will be randomized to receive elvucitabine 10 mg QD or lamivudine 300 mg QD for 14 days. Subjects must be receiving a stable antiretroviral regimen (defined as no change in antiretroviral therapy for at least 4 weeks prior to randomization) that includes lamivudine or emtricitabine. At 72 hours prior to randomization, only lamivudine or emtricitabine will be stopped for washout; subjects will continue to receive the other drugs in their prescribed regimen (background antiretroviral therapy) during the 72-hour washout period. Subjects will then be randomized to receive blinded elvucitabine or lamivudine in a 1:1 ratio and continue to receive their prescribed background antiretroviral therapy for 14 days on an outpatient basis. Subjects will be followed for an additional 14 days post-treatment for safety, unless they enroll into the ACH443-018 extension study where they will continue to be treated and followed for safety.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinically stable HIV-1 infected patients
  • Ages > 18 and < 65 years
  • Documented M184V mutation
  • CD4 cell count > 100 cells/mL
  • Plasma HIV-1 RNA levels > 5000 and < 150,000 copies/mL
  • Currently receiving lamivudine or emtricitabine
  • Other hematologic and metabolic parameters must be met.
  • Provide written informed consent
  • Other inclusion criteria apply.

Exclusion Criteria:

  • Hepatitis B antigen positive
  • HIV-1 genotype positive for more than or equal to 4 protease mutations
  • HIV-1 genotype positive for more than or equal to 2 non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations
  • Previous therapy with cytotoxic or myelosuppressive drugs in the past 3 months
  • Evidence or history of cirrhosis
  • Women who are pregnant or breast feeding
  • Other exclusion criteria apply.
  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: NCT00312039

Locations
United States, Alabama
UAB Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of California at Davis
Sacramento, California, United States, 95817
United States, Florida
University of Miami School of Medicine
Miami, Florida, United States, 33136
Orlando Immunology Center
Orlando, Florida, United States, 32803
Olayemi Osiyemi
West Palm Beach, Florida, United States, 33401
United States, Georgia
ACRA
Atlanta, Georgia, United States, 30308
United States, New York
Beth Israel Medical Center
New York, New York, United States, 10003
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45242
Sponsors and Collaborators
Achillion Pharmaceuticals
Investigators
Principal Investigator: Judith Feinberg, MD University of Cincinnati College of Pharmacy, Cincinnati, OH
Principal Investigator: Donna Mildvan, MD Beth Israel Medical Center, Infectious Diseases, Baird Hall, NY, NY
Principal Investigator: Richard Pollard, MD UC Davis Medical Center, Div. of Infectious Diseases, Sacramento, CA
Principal Investigator: Michael Saag, MD UAB Medical Center, AIDS Outpatient Clinic, Birmingham, AL
Principal Investigator: Dushyantha Jayaweera, MD University of Miami School of Medicine, Infectious Disease Research Unit, Miami, FL
Principal Investigator: Edwin DeJesus, MD Orlando Immunology Center
Principal Investigator: Melanie Thompson, MD ACRA Atlanta Georgia
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00312039     History of Changes
Other Study ID Numbers: ACH443-014A
Study First Received: April 5, 2006
Last Updated: January 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Achillion Pharmaceuticals:
HIV-1
treatment experienced

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

ClinicalTrials.gov processed this record on July 22, 2014