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

• ClinicalTrials.gov Identifier: NCT01111851
• Recruitment Status: Completed
• First Posted: April 28, 2010
• Results First Posted: November 3, 2011
• Last Update Posted: February 25, 2015
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

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.

Condition or disease	Intervention/treatment	Phase
Chemotherapy-Induced Nausea and Vomiting (CINV)	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	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: MK0869 and MK0517 Time-on-Target PET Study
• Study Start Date: April 2010
• Actual Primary Completion Date: October 2010
• Actual Study Completion Date: October 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fosaprepitant 150 mg; 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 Name: 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 Name: 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; Aprepitant 165 mg	Drug: Aprepitant 165 mg; a single oral 165 mg aprepitant capsule 15 minutes after consumption of a standard light breakfast meal; Other Name: MK0869; 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 Name: 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 250 mg; Aprepitant 250 mg	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 Name: 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 Name: 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)

Outcome Measures

Primary Outcome Measures :

1. Brain NK1-receptor Occupancy at 24 Hours Post Dose [ Time Frame: 24 hours post dose ]
2. Brain NK1-receptor Occupancy at 48 Hours Post Dose [ Time Frame: 48 hours post dose ]

Secondary Outcome Measures :

1. 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 ]
2. Brain NK1-receptor Occupancy at 120 Hours Post Dose [ Time Frame: 120 hours post dose ]

Eligibility Criteria

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

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

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Monitor; Merck Sharp & Dohme Corp.

More Information

Publications of Results:

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.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT01111851
• Other Study ID Numbers: 0869-183; 2010_531
• First Posted: April 28, 2010
• Results First Posted: November 3, 2011
• Last Update Posted: February 25, 2015
• Last Verified: February 2015

Keywords provided by Merck Sharp & Dohme Corp.:

NK1-receptor occupancy

Additional relevant MeSH terms:

Vomiting; Signs and Symptoms, Digestive; Dexamethasone; Dexamethasone acetate; Ondansetron; Aprepitant; Fosaprepitant; BB 1101; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antipruritics; Dermatologic Agents; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants