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Aprepitant and Fosaprepitant Time-on-Target PET (Positron Emission Tomography) Study (0869-183)

Primary Purpose

Chemotherapy-Induced Nausea and Vomiting (CINV)

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Fosaprepitant 150 mg
Aprepitant 165 mg
Aprepitant 250 mg
Dexamethasone (12-8-16-16 mg)
Dexamethasone (12-8-8-16 mg)
Ondansetron
MK0999
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chemotherapy-Induced Nausea and Vomiting (CINV) focused on measuring NK1-receptor occupancy

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Generally healthy
  • Female participants must be of non-childbearing potential
  • Non-smoker or has not used nicotine or nicotine-containing products for at least 6 months

Exclusion Criteria:

  • History of a clinically significant psychiatric disorder over the last 5 to 10 years
  • History of stroke, chronic seizures, or major neurological disorder
  • History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
  • History of neoplastic disease
  • Excessive consumption of alcohol (3 drinks/day) or caffeinated beverages (6 servings/day)
  • Major surgery, donated or lost 1 unit of blood within 4 weeks
  • Participated in another investigational study within 4 weeks
  • History of significant drug allergy or any clinically significant adverse

experiences related to EMEND™, dexamethasone, or ondansetron

  • History of significant multiple and/or severe allergies
  • History of anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
  • Current drug/alcohol abuse, or history of such within 2 years
  • Participation in a PET study or other study involving administration of a radioactive substance or ionizing radiation within the prior 12 months
  • Extensive radiological examination within the prior 12 months
  • Magnetizable metal prostheses or devices (Magnetic Resonance Imaging (MRI) hazard)
  • History of claustrophobia

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Fosaprepitant 150 mg

    Aprepitant 165 mg

    Aprepitant 250 mg

    Arm Description

    Fosaprepitant 150 mg

    Aprepitant 165 mg

    Aprepitant 250 mg

    Outcomes

    Primary Outcome Measures

    Brain NK1-receptor Occupancy at 24 Hours Post Dose
    Brain NK1-receptor Occupancy at 48 Hours Post Dose

    Secondary Outcome Measures

    Brain NK1-receptor Occupancy at the Time of the Maximum Concentration (Tmax)
    Brain NK1-receptor Occupancy at 120 Hours Post Dose

    Full Information

    First Posted
    April 26, 2010
    Last Updated
    February 6, 2015
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01111851
    Brief Title
    Aprepitant and Fosaprepitant Time-on-Target PET (Positron Emission Tomography) Study (0869-183)
    Official Title
    MK0869 and MK0517 Time-on-Target PET Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    April 2010 (undefined)
    Primary Completion Date
    October 2010 (Actual)
    Study Completion Date
    October 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This study will evaluate if the mean value of brain neurokinin 1 (NK1)-receptor occupancy of participants treated with aprepitant is similar to that of participants treated with fosaprepitant at certain timepoints.
    Detailed Description
    The third arm of the study (Aprepitant 250 mg) will only be conducted if the real-time assessment of the NK1-receptor occupancy data between fosaprepitant 150 mg & aprepitant 165 mg reveals that the primary hypothesis will not be supported.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chemotherapy-Induced Nausea and Vomiting (CINV)
    Keywords
    NK1-receptor occupancy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    16 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Fosaprepitant 150 mg
    Arm Type
    Experimental
    Arm Description
    Fosaprepitant 150 mg
    Arm Title
    Aprepitant 165 mg
    Arm Type
    Experimental
    Arm Description
    Aprepitant 165 mg
    Arm Title
    Aprepitant 250 mg
    Arm Type
    Experimental
    Arm Description
    Aprepitant 250 mg
    Intervention Type
    Drug
    Intervention Name(s)
    Fosaprepitant 150 mg
    Other Intervention Name(s)
    MK0517
    Intervention Description
    a single intravenous infusion of 150 mg fosaprepitant dimeglumine over 20 minutes on Day 1 15 minutes after consumption of a standard light breakfast meal
    Intervention Type
    Drug
    Intervention Name(s)
    Aprepitant 165 mg
    Other Intervention Name(s)
    MK0869
    Intervention Description
    a single oral 165 mg aprepitant capsule 15 minutes after consumption of a standard light breakfast meal
    Intervention Type
    Drug
    Intervention Name(s)
    Aprepitant 250 mg
    Other Intervention Name(s)
    MK0869
    Intervention Description
    a single oral 250 mg dose achieved by administering two 125 mg aprepitant capsules 15 minutes after consumption of a standard light breakfast meal
    Intervention Type
    Drug
    Intervention Name(s)
    Dexamethasone (12-8-16-16 mg)
    Other Intervention Name(s)
    Dexamethasone
    Intervention Description
    Dexamethasone 12 mg will be administered orally 30 minutes after the start of fosaprepitant dimeglumine or 30 minutes after aprepitant on Day 1; Oral doses of dexamethasone will be administered on Day 2 (8 mg), Day 3 (8 mg twice daily), and Day 4 (8 mg twice daily) with or without a meal.
    Intervention Type
    Drug
    Intervention Name(s)
    Dexamethasone (12-8-8-16 mg)
    Other Intervention Name(s)
    Dexamethasone
    Intervention Description
    Dexamethasone 12 mg will be administered orally 30 minutes after after aprepitant on Day 1; Oral doses of dexamethasone will be administered on Day 2 (8 mg), Day 3 (8 mg), and Day 4 (8 mg twice daily) with or without a meal.
    Intervention Type
    Drug
    Intervention Name(s)
    Ondansetron
    Intervention Description
    The intravenous (I.V.) infusion of ondansetron 32 mg will begin 30 minutes after the start of fosaprepitant dimeglumine or 30 minutes after aprepitant on Day 1 and will be administered as a 15-minute infusion
    Intervention Type
    Drug
    Intervention Name(s)
    MK0999
    Intervention Description
    I.V. infusion of MK0999 containing ~100 MBq (~3 mCi) containing ≤ 5 ug of MK0999)
    Primary Outcome Measure Information:
    Title
    Brain NK1-receptor Occupancy at 24 Hours Post Dose
    Time Frame
    24 hours post dose
    Title
    Brain NK1-receptor Occupancy at 48 Hours Post Dose
    Time Frame
    48 hours post dose
    Secondary Outcome Measure Information:
    Title
    Brain NK1-receptor Occupancy at the Time of the Maximum Concentration (Tmax)
    Time Frame
    30 minutes after the end of the 20-minute infusion of fosaprepitant or at 4 hours after oral dosing of aprepitant
    Title
    Brain NK1-receptor Occupancy at 120 Hours Post Dose
    Time Frame
    120 hours post dose

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Generally healthy Female participants must be of non-childbearing potential Non-smoker or has not used nicotine or nicotine-containing products for at least 6 months Exclusion Criteria: History of a clinically significant psychiatric disorder over the last 5 to 10 years History of stroke, chronic seizures, or major neurological disorder History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases History of neoplastic disease Excessive consumption of alcohol (3 drinks/day) or caffeinated beverages (6 servings/day) Major surgery, donated or lost 1 unit of blood within 4 weeks Participated in another investigational study within 4 weeks History of significant drug allergy or any clinically significant adverse experiences related to EMEND™, dexamethasone, or ondansetron History of significant multiple and/or severe allergies History of anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food Current drug/alcohol abuse, or history of such within 2 years Participation in a PET study or other study involving administration of a radioactive substance or ionizing radiation within the prior 12 months Extensive radiological examination within the prior 12 months Magnetizable metal prostheses or devices (Magnetic Resonance Imaging (MRI) hazard) History of claustrophobia
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Monitor
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    22739139
    Citation
    Van Laere K, De Hoon J, Bormans G, Koole M, Derdelinckx I, De Lepeleire I, Declercq R, Sanabria Bohorquez SM, Hamill T, Mozley PD, Tatosian D, Xie W, Liu Y, Liu F, Zappacosta P, Mahon C, Butterfield KL, Rosen LB, Murphy MG, Hargreaves RJ, Wagner JA, Shadle CR. Equivalent dynamic human brain NK1-receptor occupancy following single-dose i.v. fosaprepitant vs. oral aprepitant as assessed by PET imaging. Clin Pharmacol Ther. 2012 Aug;92(2):243-50. doi: 10.1038/clpt.2012.62. Epub 2012 Jun 27.
    Results Reference
    result

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    Aprepitant and Fosaprepitant Time-on-Target PET (Positron Emission Tomography) Study (0869-183)

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