Effects of Treatment With Aprepitant (Emend®) in HIV Infected Individuals. 375 mg Dose
|ClinicalTrials.gov Identifier: NCT01300988|
Recruitment Status : Completed
First Posted : February 23, 2011
Last Update Posted : June 3, 2016
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.
18 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 to receive 375 mg of aprepitant (Emend®) or placebo.
|Condition or disease||Intervention/treatment||Phase|
|HIV Infection||Drug: Aprepitant Drug: Aprepitant placebo||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|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|
|Study Start Date :||December 2010|
|Actual Primary Completion Date :||August 2013|
|Actual Study Completion Date :||August 2013|
Active Comparator: Aprepitant
Aprepitant (Emend®) 375 mg daily for 14 days
Aprepitant (Emend®) 375 mg daily for 14 days
Placebo Comparator: Placebo
Aprepitant (Emend®) placebo for 14 days
Drug: Aprepitant placebo
Aprepitant(Emend®) placebo for 14 days
- Virologic: Change in log10 HIV-1 RNA from baseline to Day 14 [ Time Frame: 14 days ]For the purposes of assessing the primary analysis of efficacy of aprepitant in reducing viral load we will be assessing the difference between the log10 viral load at baseline and at 4 weeks, and constructing a 95% confidence interval around this mean difference within each dose group.
- Safety: Incidence of Grade 2, 3, and 4 adverse events [ Time Frame: 42 days ]The frequency of grade 2,3 and 4 adverse events for the duration of the study will be measured to assess the safety of the compund in this population. Exact binomial confidence intervals will be calculated around the event rates for any individual adverse events that occur and for the overall rate of adverse events within each body system. For each patient the highest grade occurring adverse event within each body system will be assessed. Tables for adverse events by body system and severity of adverse event will be constructed.
- Pharmacokinetic [ Time Frame: 14 days ]Individual patient data will be summarized using a noncompartmental analysis (NCA) approach as well as a model-based approach.
- Immunologic [ Time Frame: 14 days ]
A descriptive analysis of the following parameters by arm at each time point will be done:
- CCR5 mRNA copy number per cell and CCR5 density by flow cytometry.
- CD4+ cell count at baseline, Days 3, 7, 10, 14, and 42.
- Time to permanent discontinuation of study treatment for any reason.
- Baseline coreceptor phenotype (CCR5, CXCR4, or mixed).
- Time to change from CCR5-only virus to mixed CCR5/CXCR4 or CXCR4-only virus as detected by the phenotype/genotype assays that will be used in this study.
- Neurologic [ Time Frame: 14 days ]Evaluate individual changes from baseline to 14 days for these subjects in the HAM-D 17 Depression Rating Scale score, the HAM-A, and the PSQI
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01300988
|United States, Pennsylvania|
|Clinical Trials Unit. University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104--607|
|Principal Investigator:||Pablo Tebas, MD||University of Pennsylvania|