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

Phase 1

Completed

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

• Registration Number: NCT00990821
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-01
• Primary Completion: 2005-12
• Study Completion: 2006-01
• Study First Submitted: 2009-10-06
• Study First Submitted QC: 2009-10-06
• Study First Posted: 2009-10-07
• Results First Submitted: 2010-04-09
• Results First Submitted QC: 2013-10-21
• Results First Posted: 2013-12-12
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-18
• Last Update Posted: 2015-08-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 188

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part I, Panel B	125 mg Aprepitant	100 mg MK-0517 (PS80 formulation \[PS80\]) or placebo → 150 mg MK-0517 (PS80) or placebo → 125 mg aprepitant
Part III, Panel 1, Treatment Sequence 1	125 mg Aprepitant	125 mg aprepitant → 90 mg MK-0517 (PS80)
Part V, Treatment Sequence 1	125 mg Aprepitant	125 mg aprepitant → 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80 formulation)
Part V, Treatment Sequence 2	125 mg Aprepitant	100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80) → 125 mg aprepitant
Part V, Treatment Sequence 3	125 mg Aprepitant	115 mg MK-0517 (PS80) → 125 mg aprepitant → 100 mg MK-0517 (PS80)
Part II	100 mg MK-0517 (PS80)	2 mg midazolam → 100 mg MK-0517 (PS80) + 2 mg midazolam
Part V, Treatment Sequence 6	100 mg MK-0517 (PS80)	115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80) → 125 mg aprepitant
Part I, Panel A	125 mg Aprepitant	100 mg MK-0517 (nonpolysorbate 80 formulation \[non-PS80\]) or placebo → 150 mg MK-0517 (non- PS80) or placebo → 125 mg aprepitant
Part I, Panel B	150 mg MK-0517 (PS80)	100 mg MK-0517 (PS80 formulation \[PS80\]) or placebo → 150 mg MK-0517 (PS80) or placebo → 125 mg aprepitant
Part I, Panel C	40 mg MK-0517 (non-PS80)	40 mg MK-0517 (non-PS80) or placebo → 40 mg aprepitant
Part II	2 mg Midazolam	2 mg midazolam → 100 mg MK-0517 (PS80) + 2 mg midazolam
Part I, Panel A	150 mg MK-0517 (Non-PS80)	100 mg MK-0517 (nonpolysorbate 80 formulation \[non-PS80\]) or placebo → 150 mg MK-0517 (non- PS80) or placebo → 125 mg aprepitant
Part I, Panel A	100 MK-0517 (PS80) + 2 mg midazolam	100 mg MK-0517 (nonpolysorbate 80 formulation \[non-PS80\]) or placebo → 150 mg MK-0517 (non- PS80) or placebo → 125 mg aprepitant
Part I, Panel A	100 mg MK-0517 (non-PS80)	100 mg MK-0517 (nonpolysorbate 80 formulation \[non-PS80\]) or placebo → 150 mg MK-0517 (non- PS80) or placebo → 125 mg aprepitant
Part IV	40 mg MK-0517 (non-PS80)	40 mg MK-0517 (non-PS80 formulation)
Part V, Treatment Sequence 4	115 mg MK-0517 (PS80)	125 mg aprepitant → 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80)
Part V, Treatment Sequence 5	100 mg MK-0517 (PS80)	100 mg MK-0517 (PS80) → 125 mg aprepitant → 115 mg MK-0517 (PS80)
Part I, Panel A	Placebo	100 mg MK-0517 (nonpolysorbate 80 formulation \[non-PS80\]) or placebo → 150 mg MK-0517 (non- PS80) or placebo → 125 mg aprepitant
Part I, Panel C	40 mg Aprepitant	40 mg MK-0517 (non-PS80) or placebo → 40 mg aprepitant
Part III, Panel 1, Treatment Sequence 1	90 mg MK-0517 (PS80)	125 mg aprepitant → 90 mg MK-0517 (PS80)
Part V, Treatment Sequence 1	115 mg MK-0517 (PS80)	125 mg aprepitant → 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80 formulation)
Part V, Treatment Sequence 6	125 mg Aprepitant	115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80) → 125 mg aprepitant
Part V, Treatment Sequence 3	100 mg MK-0517 (PS80)	115 mg MK-0517 (PS80) → 125 mg aprepitant → 100 mg MK-0517 (PS80)
Part I, Panel C	Placebo	40 mg MK-0517 (non-PS80) or placebo → 40 mg aprepitant
Part I, Panel B	100 mg MK-0517 (PS80)	100 mg MK-0517 (PS80 formulation \[PS80\]) or placebo → 150 mg MK-0517 (PS80) or placebo → 125 mg aprepitant
Part I, Panel B	Placebo	100 mg MK-0517 (PS80 formulation \[PS80\]) or placebo → 150 mg MK-0517 (PS80) or placebo → 125 mg aprepitant
Part V, Treatment Sequence 5	125 mg Aprepitant	100 mg MK-0517 (PS80) → 125 mg aprepitant → 115 mg MK-0517 (PS80)
Part III, Panel 1, Treatment Sequence 1	40 mg MK-0517 (non-PS80)	125 mg aprepitant → 90 mg MK-0517 (PS80)
Part III, Panel 1, Treatment Sequence 2	40 mg MK-0517 (non-PS80)	40 mg MK-0517 (non-PS80) → 125 mg aprepitant
Part III, Panel 1, Treatment Sequence 2	125 mg Aprepitant	40 mg MK-0517 (non-PS80) → 125 mg aprepitant
Part III, Panel 2	40 mg MK-0517 (non-PS80)	40 mg MK-0517 (non-PS80)
Part V, Treatment Sequence 1	100 mg MK-0517 (PS80)	125 mg aprepitant → 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80 formulation)
Part V, Treatment Sequence 2	100 mg MK-0517 (PS80)	100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80) → 125 mg aprepitant
Part V, Treatment Sequence 6	115 mg MK-0517 (PS80)	115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80) → 125 mg aprepitant
Part V, Treatment Sequence 4	125 mg Aprepitant	125 mg aprepitant → 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80)
Part V, Treatment Sequence 5	115 mg MK-0517 (PS80)	100 mg MK-0517 (PS80) → 125 mg aprepitant → 115 mg MK-0517 (PS80)
Part V, Treatment Sequence 2	115 mg MK-0517 (PS80)	100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80) → 125 mg aprepitant
Part V, Treatment Sequence 3	115 mg MK-0517 (PS80)	115 mg MK-0517 (PS80) → 125 mg aprepitant → 100 mg MK-0517 (PS80)
Part V, Treatment Sequence 4	100 mg MK-0517 (PS80)	125 mg aprepitant → 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80)

Primary Outcome Measures

Name	Time	Method
Area Under the Plasma-Time Curve (AUC[0 to Infinity]) for Aprepitant and MK-0517 for Study Part V	Up to 72 Hours Post Dose	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.