Effects of Treatment With Aprepitant (Emend®) in HIV Infected Individuals
The investigators' in vitro data suggest that Neurokinin-1 receptor antagonists like aprepitant will decrease the expression of CCR5, an essential co-receptor in the life cycle of HIV, in the surface of macrophages and lymphocytes to levels at least similar to those observed in patients heterozygous for the CCR5 32 mutation. Together with a direct potential antiviral effect this could alter disease progression in patients with HIV infection.
The investigators' hypothesis is that aprepitant is safe, tolerable and has antiviral activity in HIV infected individuals.
This is randomized, placebo controlled, double blind study to determine the safety and antiviral activity of aprepitant by comparing the change in HIV RNA viral load after 2 weeks of aprepitant monotherapy.
27 HIV infected males and females ≥ 18 years old who have early infection with CD4 cell counts ≥ 350 cells/mm3. Subjects will be randomized 1:1:1 to receive two different doses of aprepitant (Emend®) or placebo.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase Ib, Randomized, Placebo Controlled, Double Blind Study to Determine the Safety, Viral Suppression, Pharmacokinetics and Immune Modulatory Effects of Treatment With Aprepitant (Emend®) in HIV Infected Individuals|
- Virologic: Change in log10 HIV-1 RNA from baseline to Day 14 [ Time Frame: 14 days ] [ Designated as safety issue: No ]
- Safety: Incidence of Grade 2, 3, and 4 adverse events [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
- Pharmacokinetic [ Time Frame: 14 days ] [ Designated as safety issue: No ]
- Immunologic [ Time Frame: 14 days ] [ Designated as safety issue: No ]
- Neurologic [ Time Frame: 14 days ] [ Designated as safety issue: No ]
|Study Start Date:||January 2007|
|Study Completion Date:||December 2009|
|Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
|Placebo Comparator: 1||
Placebo for 14 days
|Active Comparator: 2||
Aprepitant at a dose of 125 mg daily for 14 days
|Active Comparator: 3||
Aprepitant at a dose of 250 mg daily for 14 days
Randomized, placebo controlled, double blind study to determine the safety and antiviral activity of aprepitant by comparing the change in HIV RNA viral load after 2 weeks of aprepitant monotherapy.
SAMPLE SIZE and POPULATION
27 HIV infected males and females ≥ 18 years old who have early infection with CD4 cell counts ≥ 350 cells/mm3.
Subjects will be randomized 1:1:1 to receive two different doses of aprepitant (Emend®) or placebo.
- Arm A: Aprepitant placebo
- Arm B: Aprepitant 125 mg QD
- Arm C: Aprepitant 250 mg QD
HYPOTHESIS AND STUDY OBJECTIVES
- Hypothesis : Aprepitant is safe, tolerable, and has antiviral activity in HIV infected individuals.
- To assess the safety and tolerability of aprepitant for 2 weeks at two different doses.
- To assess the response of plasma HIV-1 RNA to two different doses of aprepitant compared with baseline.
- To investigate the course and duration of antiretroviral response to 2 different doses of aprepitant given over a 14-day period.
- To evaluate the dose-response and pharmacokinetic and pharmacodynamic relationship between viral RNA change and aprepitant plasma levels.
- To evaluate aprepitant effects on CD4+ and CD8+ T-cell counts, circulating SP levels, natural killer cell number and function and CCR5 expression in peripheral PBMCs.
- To evaluate the effects of aprepitant in the viral tropism and envelope sequence of the main HIV-1 population of the participants.
- To assess viral drug susceptibility in conjunction with baseline coreceptor tropism phenotype and changes in coreceptor phenotype after the exposure to aprepitant.
- To evaluate aprepitant effects on fasting plasma glucose, insulin, HDL, free fatty acids, and triglyceride concentrations after 14 days of treatment.
- To provide preliminary description of any change from baseline in sleep quality, anxious mood, depressed mood and neurocognitive measures after 2 weeks of aprepitant therapy.
|United States, Pennsylvania|
|Clinical Trials Unit. University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Pablo Tebas, MD||University of Pennsylvania|