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

NCT01300988 | Completed Phase 1 DMC

• 2 other identifiers: 811938U01MH090325
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infection

Keywords

HIV infection; Neurokinin-1 receptor antagonist; CCR5 expression; Treatment Naive

Outcome Measures

Primary Outcomes (2)

• Virologic: Change in log10 HIV-1 RNA from baseline to Day 14

  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.

  14 days

• Safety: Incidence of Grade 2, 3, and 4 adverse events

  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.

  42 days

Secondary Outcomes (3)

• Pharmacokinetic

  14 days

• Immunologic

  14 days

• Neurologic

  14 days

Study Arms (2)

Aprepitant

ACTIVE COMPARATOR

Aprepitant (Emend®) 375 mg daily for 14 days

Drug: Aprepitant

Placebo

PLACEBO COMPARATOR

Aprepitant (Emend®) placebo for 14 days

Drug: Aprepitant placebo

Interventions

Aprepitant DRUG

Aprepitant (Emend®) 375 mg daily for 14 days

Aprepitant

Aprepitant placebo DRUG

Aprepitant(Emend®) placebo for 14 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Clinical Trials Unit. University of Pennsylvania

Philadelphia, Pennsylvania, 19104--607, United States

Location

Related Publications (5)

• Lai JP, Ho WZ, Zhan GX, Yi Y, Collman RG, Douglas SD. Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3970-5. doi: 10.1073/pnas.071052298.

  PMID: 11274418 BACKGROUND

• Lai JP, Ho WZ, Kilpatrick LE, Wang X, Tuluc F, Korchak HM, Douglas SD. Full-length and truncated neurokinin-1 receptor expression and function during monocyte/macrophage differentiation. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7771-6. doi: 10.1073/pnas.0602563103. Epub 2006 May 4.

  PMID: 16675550 BACKGROUND

• Ho WZ, Evans DL, Douglas SD. Substance P and Human Immunodeficiency Virus Infection: Psychoneuroimmunology. CNS Spectr. 2002 Dec;7(12):867-874. doi: 10.1017/s1092852900022483.

  PMID: 12766696 BACKGROUND

• Ho WZ, Lai JP, Li Y, Douglas SD. HIV enhances substance P expression in human immune cells. FASEB J. 2002 Apr;16(6):616-8. doi: 10.1096/fj.01-0655fje.

  PMID: 11919172 BACKGROUND

• Li Y, Douglas SD, Song L, Sun S, Ho WZ. Substance P enhances HIV-1 replication in latently infected human immune cells. J Neuroimmunol. 2001 Dec 3;121(1-2):67-75. doi: 10.1016/s0165-5728(01)00439-8.

  PMID: 11730941 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

Aprepitant

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pablo Tebas, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2010
• First Posted: February 23, 2011
• Study Start: December 1, 2010
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: June 3, 2016

Record last verified: 2016-06

Locations

US (1)