HIV Infections
Conditions
Keywords
HIV-1, treatment experienced
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.
Interventions
DRUGElvucitabine
Elvucitabine 10 mg QD for 14days
DRUGLamivudine
Lamivudine 300 mg QD for 14 days
Sponsors
Achillion, a wholly owned subsidiary of Alexion
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Reduction In Viral Load | 14 days |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants with a Treatment Adverse Event | 14 days |
Countries
United States
Outcome results
None listed