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

HIV Infections Clinical Trial

— Resistance  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00312039
• Other study ID #: ACH443-014A
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 31, 2006
• Est. completion date: October 31, 2007

Study information

• Verified date: August 2023
• Source: Alexion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 31, 2007
• Est. primary completion date: October 31, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Elvucitabine
Elvucitabine 10 mg QD for 14days
• Lamivudine
Lamivudine 300 mg QD for 14 days

Locations

Country	Name	City	State
United States	Clinical Trial Site	Atlanta	Georgia
United States	Clinical Trial Site	Birmingham	Alabama
United States	Clinical Trial Site	Cincinnati	Ohio
United States	Clinical Trial Site	Miami	Florida
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Orlando	Florida
United States	Clinical Trial Site	Sacramento	California
United States	Clinical Trial Site	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Alexion	Achillion, a wholly owned subsidiary of Alexion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction In Viral Load		14 days
Secondary	Number of Participants with a Treatment Adverse Event		14 days