Clinical Trials


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

This study has been completed
Achillion Pharmaceuticals

Information provided by (Responsible Party)
Achillion Pharmaceuticals Identifier

First received: April 5, 2006
Last updated: January 20, 2014
Last Verified: January 2014
History of Changes


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
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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

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 ]

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.



Ages Eligible for Study: 18 Years to 65 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  


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

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 identifier: NCT00312039


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
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


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

More Information

Responsible Party: Achillion Pharmaceuticals Identifier: NCT00312039   History of Changes  
Other Study ID Numbers: ACH443-014A  
Study First Received: April 5, 2006  
Last Updated: January 20, 2014  

Keywords provided by Achillion Pharmaceuticals:

treatment experienced

Additional relevant MeSH terms:
HIV Infections
Dexelvucitabine processed this data on January 23, 2020
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