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

Study Overview
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Brief Summary
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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
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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.

Official Title
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MK0869 and MK0517 Time-on-Target PET Study

Conditions
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Chemotherapy-Induced Nausea and Vomiting (CINV)

Intervention / Treatment
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* Drug: Fosaprepitant 150 mg
* Drug: Aprepitant 165 mg
* Drug: Aprepitant 250 mg
* Drug: Dexamethasone (12-8-16-16 mg)
* Drug: Dexamethasone (12-8-8-16 mg)
* Drug: Ondansetron
* Drug: MK0999


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosaprepitant 150 mg<br>Fosaprepitant 150 mg | Drug: Fosaprepitant 150 mg<br>* 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<br>* Other names: MK0517;Drug: Dexamethasone (12-8-16-16 mg)<br>* 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.<br>* Other names: Dexamethasone;Drug: Ondansetron<br>* 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<br>Drug: MK0999<br>* I.V. infusion of MK0999 containing  100 MBq ( 3 mCi) containing ≤ 5 ug of MK0999)<br>|
| Experimental: Aprepitant 165 mg<br>Aprepitant 165 mg | Drug: Aprepitant 165 mg<br>* a single oral 165 mg aprepitant capsule 15 minutes after consumption of a standard light breakfast meal<br>* Other names: MK0869;Drug: Dexamethasone (12-8-16-16 mg)<br>* 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.<br>* Other names: Dexamethasone;Drug: Ondansetron<br>* 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<br>Drug: MK0999<br>* I.V. infusion of MK0999 containing  100 MBq ( 3 mCi) containing ≤ 5 ug of MK0999)<br>|
| Experimental: Aprepitant 250 mg<br>Aprepitant 250 mg | Drug: Aprepitant 250 mg<br>* a single oral 250 mg dose achieved by administering two 125 mg aprepitant capsules 15 minutes after consumption of a standard light breakfast meal<br>* Other names: MK0869;Drug: Dexamethasone (12-8-8-16 mg)<br>* 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.<br>* Other names: Dexamethasone;Drug: Ondansetron<br>* 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<br>Drug: MK0999<br>* I.V. infusion of MK0999 containing  100 MBq ( 3 mCi) containing ≤ 5 ug of MK0999)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain NK1-receptor Occupancy at 24 Hours Post Dose |  | 24 hours post dose | 
| Brain NK1-receptor Occupancy at 48 Hours Post Dose |  | 48 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain NK1-receptor Occupancy at the Time of the Maximum Concentration (Tmax) |  | 30 minutes after the end of the 20-minute infusion of fosaprepitant or at 4 hours after oral dosing of aprepitant | 
| Brain NK1-receptor Occupancy at 120 Hours Post Dose |  | 120 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NK1-receptor occupancy