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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Elvucitabine
* Drug: Lamivudine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: Elvucitabine<br>* Elvucitabine 10 mg QD for 14days<br>|
| Active Comparator: B<br> | Drug: Lamivudine<br>* Lamivudine 300 mg QD for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction In Viral Load |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with a Treatment Adverse Event |  | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, treatment experienced