Effects of Treatment With Aprepitant (Emend®) in HIV Infected Individuals

NCT00428519 | Completed Phase 1 DMC

• 2 other identifiers: 75558U01MH090325
• Study Type: interventional
• Target: 30
• 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. 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.

Conditions

HIV Infections

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

  14 days

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

  42 days

Secondary Outcomes (3)

• Pharmacokinetic

  14 days

• Immunologic

  14 days

• Neurologic

  14 days

Study Arms (3)

1

PLACEBO COMPARATOR

Drug: Placebo

2

ACTIVE COMPARATOR

Drug: Aprepitant

3

ACTIVE COMPARATOR

Drug: Aprepitant

Interventions

Placebo DRUG

Placebo for 14 days

1

Aprepitant DRUG

Aprepitant at a dose of 125 mg daily for 14 days

2

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 any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
• CD4+ cell count ≥ 350/mm3 obtained within 90 days prior to study entry and performed at any CLIA-certified laboratory.
• Plasma HIV-1 RNA of ≥ 2000 copies/mL as measured by any standard assay (the Roche UltraSensitive HIV-1 Monitor assay (Roche Molecular Systems), or Version 3 bDNA assay or other) and performed within 90 days prior to study entry by any laboratory that is CLIA-certified (or its equivalent) for the assay.
• CCR5 tropic virus exclusively as determined by the Monogram tropism assay (PhenoSense Entry™).
• Laboratory values obtained within 30 days prior to study entry, as follows:
• Absolute neutrophil count (ANC) greater than 750/mm3
• Hemoglobin greater than 10.0 g/dL
• Platelet count greater than 100,000/mm3
• Creatinine less than 2 x ULN (fasting)
• AST (SGOT), ALT (SGPT), and alkaline phosphatase less than 2 x ULN
• Total bilirubin less than 2.5 x ULN
• Albumin greater than 3 g/dL
• Serum lipase less than 1.5 x ULN
• 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.

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-Plug 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, United States

Location

Related Publications (7)

• 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

• Tebas P, Tuluc F, Barrett JS, Wagner W, Kim D, Zhao H, Gonin R, Korelitz J, Douglas SD. A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults. PLoS One. 2011;6(9):e24180. doi: 10.1371/journal.pone.0024180. Epub 2011 Sep 8.

  PMID: 21931661 RESULT

• Tebas P, Spitsin S, Barrett JS, Tuluc F, Elci O, Korelitz JJ, Wagner W, Winters A, Kim D, Catalano R, Evans DL, Douglas SD. Reduction of soluble CD163, substance P, programmed death 1 and inflammatory markers: phase 1B trial of aprepitant in HIV-1-infected adults. AIDS. 2015 May 15;29(8):931-9. doi: 10.1097/QAD.0000000000000638.

  PMID: 25915168 RESULT

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2007
• First Posted: January 30, 2007
• Study Start: January 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: March 30, 2017

Record last verified: 2017-03

Locations

US (1)