Pharmacokinetic (PK) Characteristics and Anti-Inflammatory Effects of the NK-1R Antagonist, Aprepitant, In HIV-Infected Subjects With Undetectable Viral Load Receiving Atazanavir/Ritonavir Or Darunavir/Ritonavir-Containing Antiretroviral Therapy (Emend IV)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Pennsylvania
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT02154360
First received: May 22, 2014
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

This is an open-label, single arm, phase I study to determine the safety, PK characteristics and anti-inflammatory effects of the NK-R1 coadministered with ritonavir-containing antiretroviral therapy in individuals with well-controlled viral replication.

Our hypothesis is that Aprepitant will be safe, well tolerated, and will have anti-inflammatory properties when administered concomitantly with the protease inhibitor ritonavir.


Condition Intervention Phase
HIV Infection
Drug: Aprepitant
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: EMEND IV A Phase IB, Open Label Study to Examine the Safety, Pharmacokinetic (PK) Characteristics and Anti-Inflammatory Effects of the NK-1R Antagonist, Aprepitant, In HIV-Infected Subjects With Undetectable Viral Load Receiving Atazanavir/Ritonavir Or Darunavir/Ritonavir-Containing Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Inflammatory [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Change in levels of Soluble CD163 from baseline to Day 14.

  • Safety [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Incidence of Grade 2, 3, and 4 adverse events (using the DAIDS grading scale) by body system and by type. Lack of virologic control is considered a safety event for the purpose of this trial.

  • Pharmacokinetic Cmin: [ Time Frame: day 1, 14 and 28 ] [ Designated as safety issue: No ]
    Trough plasma aprepitant concentration.

  • Pharmacokinetic Cmax [ Time Frame: day 1, 14 and 28 ] [ Designated as safety issue: No ]
    Maximum plasma concentration.

  • Pharmacokinetic Tmax [ Time Frame: day 1, 14 and 28 ] [ Designated as safety issue: No ]
    Time to maximum plasma concentration

  • Pharmacokinetic AUCss [ Time Frame: day 1, 14 and 28 ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve at steady-state (based on steady-state assessment of trough concentrations or via modeling).


Secondary Outcome Measures:
  • Inflammatory markers [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    • Change in levels of Soluble CD163 from baseline to Day 28 and 58
    • Plasma SP levels
    • CD4/PD-1 expression

  • Lipids [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    • Triglycerides
    • Total cholesterol
    • HDL
    • LDL
    • Insulin

  • Neurological [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    • Hamilton-17 Depression Rating Scale (HAM-D-17) score
    • Hamilton- Anxiety Symptoms (HAM-A) score
    • Pittsburgh Sleep Quality Index (PSQI) score


Estimated Enrollment: 12
Study Start Date: May 2014
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aprepitant

Subjects will add 375 mg daily dosing of aprepitant (Emend®) to their current antiretroviral therapy for 28 days.

  • 6 participants will be receiving an antiretroviral regimen containing atazanavir/ritonavir (300/100 mg) daily plus two other antiretrovirals.
  • 6 participants will be receiving an antiretroviral regimen containing darunavir/ritonavir (800/100 mg) daily plus two other antiretrovirals.
Drug: Aprepitant
Subjects will add 375 mg daily dosing of aprepitant (Emend®) to their current antiretroviral therapy for 28 days
Other Name: Emend

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Antiretroviral treatment with a regimen that includes either atazanavir 300 mg daily with ritonavir 100 mg daily or darunavir/ritonavir on a combination of 800/100 mg daily for at least 6 months prior to enrollment.
  3. CD4+ cell count ≥ 350/mm3 for at least 6 months prior to enrollment and performed at any CLIA-certified laboratory.
  4. Plasma HIV-1 RNA below the limit of quantification of an ultrasensitive assay as measured by any standard assay (the Roche Amplicor, the UltraSensitive HIV-1 Monitor assay (Roche Molecular Systems), or Version 3 bDNA assay or other) for at least 6 months prior to enrollment by any laboratory that is CLIA-certified (or its equivalent) for the assay.
  5. Laboratory values obtained within 30 days prior to study entry, as follows:

    • Absolute neutrophil count (ANC) greater or equal than 750/mm3
    • Hemoglobin greater or equal than 10.0 g/dL
    • Platelet count greater or equal than 100,000/mm3
    • Creatinine less or equal than 2 x ULN (fasting)
    • AST (SGOT), ALT (SGPT), and alkaline phosphatase less or equal than 2 x ULN
    • Total bilirubin less or equal than 2.5 x ULN
    • Albumin greater or equal than 3 g/dL
  6. 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.
  7. All subjects must agree not to participate in a conception process while on study drug and for 30 days after stopping the medication.

    If participating in sexual activity that could lead to pregnancy, the female study subject must use at least one of the forms of contraception listed below while receiving the protocol-specified medication and for 30 days after stopping the medication.

    • Condoms (male or female) with or without a spermicidal agent
    • Diaphragm or cervical cap with spermicide
    • IUD

    Female subjects, who are not of reproductive potential defined as women who have been post-menopausal for at least 24 consecutive months, or women who have undergone surgical sterilization, (e.g. hysterectomy, bilateral oophorectomy, or salpingotomy) are eligible without requiring the use of contraception. Subject reported history is acceptable for documentation of sterilization, other contraceptive methods, menopause and a female's reproductive potential.

  8. Karnofsky performance score greater or equal than 80 within 30 days prior to study entry (Appendix I).
  9. Men and women greater or equal than 18 years of age.
  10. Ability and willingness of subject or legal guardian/representative to give written informed consent.
  11. Willing to return for a follow-up visit on day 58.
  12. 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:

  1. Diabetes requiring treatment with oral hypoglycemics or insulin therapy.
  2. Pregnancy within 90 days prior to study entry.
  3. Use of inhibitors of metabolism by the cytochrome P450 3A4 with the exception of ritonavir, atazanavir and darunavir (i.e. Diltiazem, Ketoconazole, Clarithromycin, Nelfinavir, Itraconazole, Nefazodone, Troleandomycin)
  4. Use of inducers of metabolism by the cytochrome P450 3A4 (i.e.: Rifampin, Carbamazepine, Phenytoin) with the exception of the protease inhibitors considered in this trial.
  5. Breast-feeding.
  6. Use of systemic corticosteroids or hormonal agents within 90 days prior to study entry.
  7. Use of any immunomodulator, HIV vaccines, or investigational therapy within 90 days prior to study entry. However, if the experimental agent has a short half life, as determined by the Principal Investigator, the required wash out period can be reduced to 30 days.
  8. Any vaccination within 30 days prior to study entry.
  9. Use of systemic cytotoxic chemotherapy within 90 days prior to study entry.
  10. History of allergy to aprepitant or its formulations.
  11. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
  12. History of chronic active hepatitis B or C infection or severe hepatic dysfunction (Child-Pugh score > 9) regardless of etiology
  13. 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.
  14. Weight < 40 kg or 88 lbs. within 90 days prior to study entry.
  15. History of severe psychiatric comorbidities, such as depression, schizophrenia, mania, psychosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02154360

Locations
United States, Pennsylvania
Hospital of the University of Pennsylvania Clinical Research Site Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Wayne Wagner, RN    215-349-8091    Wayne.Wagner@uphs.upenn.edu   
Contact: Joseph Quinn, RN    2153498091    joseph.quinn@uphs.upenn.edu   
Principal Investigator: Pablo Tebas, MD         
Sponsors and Collaborators
University of Pennsylvania
  More Information

Publications:
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02154360     History of Changes
Other Study ID Numbers: UPenn 819693
Study First Received: May 22, 2014
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
HIV infection
NK-1R antagonists
aprepitant
ritonavir boosting

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Anti-Inflammatory Agents
Ritonavir
Atazanavir
Darunavir
Fosaprepitant
Aprepitant
Therapeutic Uses
Pharmacologic Actions
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on August 27, 2014