A Study to Investigate the Safety and Tolerability of MK-0517 in Healthy Subjects (MK-0517-012)

A Randomized, 5-Part, Intravenous Study of the Safety, Tolerability, Bioequivalence, and Drug Interaction Potential of Final Market Image Formulation of MK0517 in Young Healthy Subjects

This 5-part study will evaluate the safety, tolerability, and pharmacokinetics of two formulations of MK-0517 (with and without polysorbate 80) and aprepitant in healthy adults. Parts I to IV of this study will examine different doses of MK-0517 as well as two different formulations of MK-0517 (with and without polysorbate 80). Part V of the study will compare single doses of intravenous non-PS80 MK-0517 to oral 125-mg capsule of aprepitant. The primary hypothesis for Part V of the study is that a single intravenous dose of 100-mg or 115-mg MK-0517 is area under the plasma-time curve (AUC) equivalent to that of the 125-mg oral aprepitant capsule in young healthy participants.

Study Overview

• Status: Completed
• Conditions: Postoperative Nausea and Vomiting; Chemotherapy-Induced Nausea and Vomiting
• Intervention / Treatment: Drug: 100 MK-0517 (PS80) + 2 mg midazolam; Drug: 100 mg MK-0517 (non-PS80); Drug: 150 mg MK-0517 (Non-PS80); Drug: Placebo; Drug: 125 mg Aprepitant; Drug: 100 mg MK-0517 (PS80); Drug: 150 mg MK-0517 (PS80); Drug: 40 mg MK-0517 (non-PS80); Drug: 40 mg Aprepitant; Drug: 2 mg Midazolam; Drug: 90 mg MK-0517 (PS80); Drug: 115 mg MK-0517 (PS80)

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is neither grossly overweight nor underweight for his/her height and body build
• Subject is in good health -Subject is a nonsmoker
• Subject is willing to avoid excessive alcohol consumption for the duration of the study
• Subject is willing to avoid strenuous physical activity (i.e. unaccustomed weight lifting, running, bicycling) for the duration of the study
• Subject agrees to refrain from consumption of grapefruit (and grapefruit products) before and during the study

Exclusion Criteria:

• Subject has a history of multiple and/or severe allergies to drugs or food
• Subject has donated blood or taken an investigational drug in another clinical trial within the last 4 weeks
• Subject has an infection, including Human immunodeficiency virus (HIV) infection
• Subject is a regular user of any illicit drug
• Subject consumes excessive amounts of alcohol
• Subject drinks excessive amounts of coffee, tea, cola or other caffeinated beverages
• Subject currently uses on a regular basis, any prescription or non prescription medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part I, Panel A; 100 mg MK-0517 (nonpolysorbate 80 formulation [non-PS80]) or placebo → 150 mg MK-0517 (non- PS80) or placebo → 125 mg aprepitant	Drug: 100 MK-0517 (PS80) + 2 mg midazolam; MK-0517 (Non-PS80 formulation), 1 mg/mL, administered IV over 15 minutes. Midazolam is co-administered as a single oral 2-mg dose of midazolam with MK-0517.; Drug: 100 mg MK-0517 (non-PS80); MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.; Drug: 150 mg MK-0517 (Non-PS80); MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.; Drug: Placebo; Placebo matching MK-0517; Drug: 125 mg Aprepitant; Aprepitant oral tablet, single dose
EXPERIMENTAL: Part I, Panel B; 100 mg MK-0517 (PS80 formulation [PS80]) or placebo → 150 mg MK-0517 (PS80) or placebo → 125 mg aprepitant	Drug: Placebo; Placebo matching MK-0517; Drug: 125 mg Aprepitant; Aprepitant oral tablet, single dose; Drug: 100 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes; Drug: 150 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes
EXPERIMENTAL: Part I, Panel C; 40 mg MK-0517 (non-PS80) or placebo → 40 mg aprepitant	Drug: Placebo; Placebo matching MK-0517; Drug: 40 mg MK-0517 (non-PS80); MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.; Drug: 40 mg Aprepitant; Aprepitant, oral, tablet, single dose
EXPERIMENTAL: Part II; 2 mg midazolam → 100 mg MK-0517 (PS80) + 2 mg midazolam	Drug: 100 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes; Drug: 2 mg Midazolam; Midazolam oral tablet, single dose
EXPERIMENTAL: Part III, Panel 1, Treatment Sequence 1; 125 mg aprepitant → 90 mg MK-0517 (PS80)	Drug: 125 mg Aprepitant; Aprepitant oral tablet, single dose; Drug: 40 mg MK-0517 (non-PS80); MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.; Drug: 90 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered intravenous (IV) over 15 minutes
EXPERIMENTAL: Part III, Panel 1, Treatment Sequence 2; 40 mg MK-0517 (non-PS80) → 125 mg aprepitant	Drug: 125 mg Aprepitant; Aprepitant oral tablet, single dose; Drug: 40 mg MK-0517 (non-PS80); MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.
EXPERIMENTAL: Part III, Panel 2; 40 mg MK-0517 (non-PS80)	Drug: 40 mg MK-0517 (non-PS80); MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.
EXPERIMENTAL: Part IV; 40 mg MK-0517 (non-PS80 formulation)	Drug: 40 mg MK-0517 (non-PS80); MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.
EXPERIMENTAL: Part V, Treatment Sequence 1; 125 mg aprepitant → 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80 formulation)	Drug: 125 mg Aprepitant; Aprepitant oral tablet, single dose; Drug: 100 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes; Drug: 115 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes
EXPERIMENTAL: Part V, Treatment Sequence 2; 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80) → 125 mg aprepitant	Drug: 125 mg Aprepitant; Aprepitant oral tablet, single dose; Drug: 100 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes; Drug: 115 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes
EXPERIMENTAL: Part V, Treatment Sequence 3; 115 mg MK-0517 (PS80) → 125 mg aprepitant → 100 mg MK-0517 (PS80)	Drug: 125 mg Aprepitant; Aprepitant oral tablet, single dose; Drug: 100 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes; Drug: 115 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes
EXPERIMENTAL: Part V, Treatment Sequence 4; 125 mg aprepitant → 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80)	Drug: 125 mg Aprepitant; Aprepitant oral tablet, single dose; Drug: 100 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes; Drug: 115 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes
EXPERIMENTAL: Part V, Treatment Sequence 5; 100 mg MK-0517 (PS80) → 125 mg aprepitant → 115 mg MK-0517 (PS80)	Drug: 125 mg Aprepitant; Aprepitant oral tablet, single dose; Drug: 100 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes; Drug: 115 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes
EXPERIMENTAL: Part V, Treatment Sequence 6; 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80) → 125 mg aprepitant	Drug: 125 mg Aprepitant; Aprepitant oral tablet, single dose; Drug: 100 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes; Drug: 115 mg MK-0517 (PS80); MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma-Time Curve (AUC[0 to Infinity]) for Aprepitant and MK-0517 for Study Part V	AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time. The AUC(0-inf) bioequivalence was evaluated for single doses of 100 and 115 mg MK-0517 PS80, IV and that of an oral 125-mg capsule of aprepitant. Period I to IV populations are not included in the outcome analysis because those were formulation and dose-finding/dose confirmation arms.	Up to 72 Hours Post Dose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (ACTUAL): December 1, 2005
• Study Completion (ACTUAL): January 1, 2006

Study Registration Dates

• First Submitted: October 6, 2009
• First Submitted That Met QC Criteria: October 6, 2009
• First Posted (ESTIMATE): October 7, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): August 19, 2015
• Last Update Submitted That Met QC Criteria: August 18, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Antiemetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Neurokinin-1 Receptor Antagonists; Midazolam; Aprepitant; Fosaprepitant
• Other Study ID Numbers: 0517-012; MK-0517-012