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
About this trial
This is an interventional treatment trial for Chemotherapy-Induced Nausea and Vomiting (CINV) focused on measuring NK1-receptor occupancy
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
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
NCT ID
NCT01111851
First Posted
April 26, 2010
Last Updated
February 6, 2015
Sponsor
Merck Sharp & Dohme LLC
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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