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

A 14 Day Randomized, Double-blind, Study of Once Daily Elvucitabine Versus Lamivudine in Participants With a Documented M184V Mutation

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.

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.

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.