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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01111851
First received: April 26, 2010
Last updated: May 14, 2014
Last verified: May 2014
  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:


Further study details as provided by Merck Sharp & Dohme Corp.:

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01111851     History of Changes
Other Study ID Numbers: 0869-183, 2010_531
Study First Received: April 26, 2010
Results First Received: September 29, 2011
Last Updated: May 14, 2014
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP

Keywords provided by Merck Sharp & Dohme Corp.:
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 July 24, 2014