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

NCT ID: NCT01111851

Last Updated: 2015-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2010-10-31

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.

Conditions

Chemotherapy-Induced Nausea and Vomiting (CINV)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fosaprepitant 150 mg

Fosaprepitant 150 mg

Group Type: EXPERIMENTAL

Fosaprepitant 150 mg

Intervention Type: DRUG

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

Dexamethasone (12-8-16-16 mg)

Intervention Type: DRUG

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.

Ondansetron

Intervention Type: DRUG

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

MK0999

Intervention Type: DRUG

I.V. infusion of MK0999 containing \~100 MBq (\~3 mCi) containing ≤ 5 ug of MK0999)

Aprepitant 165 mg

Aprepitant 165 mg

Group Type: EXPERIMENTAL

Aprepitant 165 mg

Intervention Type: DRUG

a single oral 165 mg aprepitant capsule 15 minutes after consumption of a standard light breakfast meal

Dexamethasone (12-8-16-16 mg)

Intervention Type: DRUG

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.

Ondansetron

Intervention Type: DRUG

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

MK0999

Intervention Type: DRUG

I.V. infusion of MK0999 containing \~100 MBq (\~3 mCi) containing ≤ 5 ug of MK0999)

Aprepitant 250 mg

Aprepitant 250 mg

Group Type: EXPERIMENTAL

Aprepitant 250 mg

Intervention Type: DRUG

a single oral 250 mg dose achieved by administering two 125 mg aprepitant capsules 15 minutes after consumption of a standard light breakfast meal

Dexamethasone (12-8-8-16 mg)

Intervention Type: DRUG

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.

Ondansetron

Intervention Type: DRUG

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

MK0999

Intervention Type: DRUG

I.V. infusion of MK0999 containing \~100 MBq (\~3 mCi) containing ≤ 5 ug of MK0999)

Interventions

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

Intervention Type: DRUG

Aprepitant 165 mg

a single oral 165 mg aprepitant capsule 15 minutes after consumption of a standard light breakfast meal

Intervention Type: 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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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

Intervention Type: DRUG

MK0999

I.V. infusion of MK0999 containing \~100 MBq (\~3 mCi) containing ≤ 5 ug of MK0999)

Intervention Type: DRUG

Other Intervention Names

MK0517; MK0869; MK0869; Dexamethasone; Dexamethasone

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 22739139 (View on PubMed)

Other Identifiers

2010_531

Identifier Type: -

Identifier Source: secondary_id

0869-183

Identifier Type: -

Identifier Source: org_study_id