Clinical trial NCT00312039: Study of Once Daily Elvucitabine Versus Lamivudine in Participants With a Documented M184V Mutation
Official title: A 14 Day Randomized, Double-blind, Study of Once Daily Elvucitabine Versus Lamivudine in Participants With a Documented M184V Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infections
Keywords: HIV-1
treatment experienced
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Achillion, a wholly owned subsidiary of Alexion
First posted: 2006-04-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Reduction In Viral Load
timeFrame: 14 days
Secondary outcomes:
measure: Number of Participants with a Treatment Adverse Event
timeFrame: 14 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Trial Site
state: Alabama
city: Sacramento
country: United States
facility: Clinical Trial Site
state: California
city: Miami
country: United States
facility: Clinical Trial Site
state: Florida
city: Orlando
country: United States
facility: Clinical Trial Site
state: Florida
city: West Palm Beach
country: United States
facility: Clinical Trial Site
state: Florida
city: Atlanta
country: United States
facility: Clinical Trial Site
state: Georgia
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Cincinnati
country: United States
facility: Clinical Trial Site
state: Ohio
Study officials:
References: