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

MK0869 and MK0517 Time-on-Target PET Study

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.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-Induced Nausea and Vomiting (CINV)
• Intervention / Treatment: Drug: Fosaprepitant 150 mg; Drug: Dexamethasone (12-8-16-16 mg); Drug: Ondansetron; Drug: MK0999; Drug: Aprepitant 165 mg; Drug: Aprepitant 250 mg; Drug: Dexamethasone (12-8-8-16 mg)

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: April 26, 2010
• First Submitted That Met QC Criteria: April 26, 2010
• First Posted (Estimate): April 28, 2010

Study Record Updates

• Last Update Posted (Estimate): February 25, 2015
• Last Update Submitted That Met QC Criteria: February 6, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: NK1-receptor occupancy
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Antipruritics; Neurokinin-1 Receptor Antagonists; Dexamethasone; Dexamethasone acetate; BB 1101; Ondansetron; Aprepitant; Fosaprepitant
• Other Study ID Numbers: 0869-183; 2010_531