Effects of Treatment With Aprepitant (Emend®) in HIV Infected Individuals. 375 mg Dose

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01300988
Recruitment Status : Completed
First Posted : February 23, 2011
Last Update Posted : June 3, 2016
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
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
Study Start Date : December 2010
Actual Primary Completion Date : August 2013
Actual Study Completion Date : August 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: Aprepitant
Aprepitant (Emend®) 375 mg daily for 14 days
Drug: Aprepitant
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

Primary Outcome Measures :
  1. 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.

  2. 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.

Secondary Outcome Measures :
  1. Pharmacokinetic [ Time Frame: 14 days ]
    Individual patient data will be summarized using a noncompartmental analysis (NCA) approach as well as a model-based approach.

  2. 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.

  3. 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

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • HIV-1 infection, as documented by a rapid HIV test or any FDA-Approved HIV-1 Enzyme or Chemiluminescence Immunoassay (E/CIA) test kit and confirmed by Western blot at any time prior to study entry.
  • CD4+ cell count >= 350/mm3 obtained within 90 days prior to study entry
  • Plasma HIV-1 RNA of >=2,000 copies/mL as measured by any standard assay and performed within 90 days prior to study entry.
  • CCR5 tropic virus exclusively as determined by the Monogram tropism assay (PhenoSense Entry™) to be performed within 90 days of study entry.
  • Laboratory values obtained within 30 days prior to study entry, as follows:

    • Absolute neutrophil count (ANC) >= 750/mm3
    • Hemoglobin >= 10.0 g/dL
    • Platelet count >= 100,000/mm3
    • Creatinine <= 2 x ULN
    • AST (SGOT), ALT (SGPT), and alkaline phosphatase <= 2 x ULN
    • Total bilirubin <= 2.5 x ULN
    • Albumin >= 3 g/dL
  • Female subjects of reproductive potential must have a negative spot urine pregnancy test result (with a sensitivity of at least 50 mIU/mL) performed at entry, prior to starting initial study treatment.
  • All subjects must agree not to participate in a conception process while on study drug and for 30 days after stopping the medication.
  • Karnofsky performance score >= 80 within 30 days prior to study entry.
  • Men and women > 18 years of age.
  • Ability and willingness of subject to give written informed consent.
  • Willing to return for a follow-up visit on day 42.
  • Subjects taking any precautionary concomitant medications must be on stable doses for >8 weeks prior to study entry and have no plans to change medications or doses for the duration of the study.

Exclusion Criteria:

  • Receipt of antiretroviral treatment within the 16 weeks prior to study entry or intent to initiate antiretroviral therapy within 60 days after entry.
  • Diabetes requiring treatment with oral hypoglycemics or insulin therapy.
  • Pregnancy within 90 days prior to study entry.
  • Breast-feeding.
  • Use of drugs that are inhibitors or inducers of metabolism by the cytochrome P450 CYP3A4 or CYP2C9 (such as warfarin and phenytoin) within 7 days of study entry.
  • Use of systemic corticosteroids or hormonal agents within 90 days prior to study entry.
  • Use of any immunomodulator, HIV vaccines, or investigational therapy within 90 days prior to study entry.
  • Any vaccination within 30 days prior to study entry.
  • Use of systemic cytotoxic chemotherapy within 90 days prior to study entry.
  • History of allergy to aprepitant or its formulations.
  • Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
  • History of chronic active hepatitis B or C infection or severe hepatic dysfunction (Child-Pugh score > 9) regardless of etiology
  • Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 14 days prior to study entry.
  • Weight < 40 kg or 88 lbs. within 90 days prior to study entry.
  • History of severe psychiatric comorbidities, such as depression, schizophrenia, mania, psychosis.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01300988

United States, Pennsylvania
Clinical Trials Unit. University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104--607
Sponsors and Collaborators
University of Pennsylvania
National Institute of Mental Health (NIMH)
Principal Investigator: Pablo Tebas, MD University of Pennsylvania

Responsible Party: University of Pennsylvania Identifier: NCT01300988     History of Changes
Other Study ID Numbers: 811938
U01MH090325 ( U.S. NIH Grant/Contract )
First Posted: February 23, 2011    Key Record Dates
Last Update Posted: June 3, 2016
Last Verified: June 2016

Keywords provided by University of Pennsylvania:
HIV infection
Neurokinin-1 receptor antagonist
CCR5 expression
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Neurokinin-1 Receptor Antagonists
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action