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

Alexion Pharmaceuticals

Status and phase

Completed

Phase 2

Phase 1

Conditions

HIV Infections

Treatments

Drug: Lamivudine

Drug: Elvucitabine

Study type

Interventional

Funder types

Industry

Identifiers

NCT00312039

ACH443-014A

Details and patient eligibility

About

Human immunodeficiency virus (HIV)-1 infected participants 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 the concentration of drug producing 50% inhibition [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. Alexion Pharmaceuticals Inc. intention is to demonstrate that 10 milligrams (mg) of elvucitabine, administered once per day for 14 days with continued background anti-HIV-1 medications, will demonstrate a fall in HIV-1 ribonucleic acid (RNA) plasma levels, as compared to baseline. The data from this study will guide dosing in future long-term studies in HIV-1 infected participants with the M184V mutation.

Full description

This was a Phase 2a, 14-Day randomized, double-blind, comparative viral kinetic study of10 mg elvucitabine as compared to lamivudine that was administered once daily (QD) to HIV-1 infected participants with a documented M184V variant. This study also demonstrated the antiviral activity as well as the assessment of safety of the elvucitabine therapy

Participants 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; participants will continue to receive the other drugs in their prescribed regimen (background antiretroviral therapy) during the 72-hour washout period. Participants 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. Participants will be followed for an additional 14 days post-treatment for safety unless they enroll in the ACH443-018 extension study where they will continue to be treated and followed for safety.

Enrollment

20 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Clinically stable HIV-1 infected participants
Ages >18 and <65 years
Documented M184V mutation
CD4 cell count >100 cells/mL
Plasma HIV-1 RNA levels >5000 and <150,000 copies/milliliter (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.