Clinical trial NCT01111851: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chemotherapy-Induced Nausea and Vomiting (CINV)
Keywords: NK1-receptor occupancy
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-04-28
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Brain NK1-receptor Occupancy at 24 Hours Post Dose
timeFrame: 24 hours post dose
measure: Brain NK1-receptor Occupancy at 48 Hours Post Dose
timeFrame: 48 hours post dose
Secondary outcomes:
measure: Brain NK1-receptor Occupancy at the Time of the Maximum Concentration (Tmax)
timeFrame: 30 minutes after the end of the 20-minute infusion of fosaprepitant or at 4 hours after oral dosing of aprepitant
measure: Brain NK1-receptor Occupancy at 120 Hours Post Dose
timeFrame: 120 hours post dose
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
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.