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

Purpose

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	Intervention	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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	MK0869 and MK0517 Time-on-Target PET Study

Resource links provided by NLM:

MedlinePlus related topics: Nausea and Vomiting

Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone sodium phosphate Ondansetron hydrochloride Ondansetron Aprepitant Fosaprepitant Fosaprepitant dimeglumine

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Brain NK1-receptor Occupancy at 24 Hours Post Dose [ Time Frame: 24 hours post dose ] [ Designated as safety issue: No ]
Brain NK1-receptor Occupancy at 48 Hours Post Dose [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
Brain NK1-receptor Occupancy at 120 Hours Post Dose [ Time Frame: 120 hours post dose ] [ Designated as safety issue: No ]

Enrollment:	16
Study Start Date:	April 2010
Study Completion Date:	October 2010
Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Other Name: Ondansetron Drug: MK0999 I.V. infusion of MK0999 containing ~100 MBq (~3 mCi) containing ≤ 5 ug of MK0999) Other Name: 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 Other Name: Ondansetron Drug: MK0999 I.V. infusion of MK0999 containing ~100 MBq (~3 mCi) containing ≤ 5 ug of MK0999) Other Name: 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 Other Name: Ondansetron Drug: MK0999 I.V. infusion of MK0999 containing ~100 MBq (~3 mCi) containing ≤ 5 ug of MK0999) Other Name: MK0999

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

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01111851

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

No publications provided

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT01111851 History of Changes
Other Study ID Numbers:	MK-0869-183, 2010_531
Study First Received:	April 26, 2010
Results First Received:	September 29, 2011
Last Updated:	September 29, 2011
Health Authority:	Belgium: Directorate general for the protection of Public health: Medicines

Keywords provided by Merck:

NK1-receptor occupancy

Additional relevant MeSH terms:

Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Dexamethasone acetate
Dexamethasone
Ondansetron
Aprepitant
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents

Physiological Effects of Drugs
Central Nervous System Agents
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

ClinicalTrials.gov processed this record on May 22, 2013