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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Chemotherapy-Induced Nausea and Vomiting, Postoperative Nausea and Vomiting

Intervention / Treatment
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* Drug: 90 mg MK-0517 (PS80)
* Drug: 100 mg MK-0517 (PS80)
* Drug: 100 MK-0517 (PS80) + 2 mg midazolam
* Drug: 115 mg MK-0517 (PS80)
* Drug: 150 mg MK-0517 (PS80)
* Drug: 40 mg MK-0517 (non-PS80)
* Drug: 100 mg MK-0517 (non-PS80)
* Drug: 150 mg MK-0517 (Non-PS80)
* Drug: Placebo
* Drug: 40 mg Aprepitant
* Drug: 125 mg Aprepitant
* Drug: 2 mg Midazolam


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |