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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Chemotherapy-Induced Nausea and Vomiting; Postoperative Nausea and Vomiting

Treatments: Drug: 150 mg MK-0517 (PS80); Drug: 100 mg MK-0517 (PS80); Drug: 100 MK-0517 (PS80) + 2 mg midazolam; Drug: 40 mg MK-0517 (non-PS80); Drug: 2 mg Midazolam; Drug: 90 mg MK-0517 (PS80); Drug: 125 mg Aprepitant; Drug: 115 mg MK-0517 (PS80); Drug: 100 mg MK-0517 (non-PS80); Drug: 150 mg MK-0517 (Non-PS80); Drug: 40 mg Aprepitant; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00990821

0517-012

MK-0517-012

Details and patient eligibility

About

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.

Enrollment: 188 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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188 participants in 14 patient groups

Part I, Panel A

Experimental group

Description:

100 mg MK-0517 (nonpolysorbate 80 formulation \[non-PS80\]) or placebo → 150 mg MK-0517 (non- PS80) or placebo → 125 mg aprepitant

Treatment:

Drug: 150 mg MK-0517 (Non-PS80)

Drug: 125 mg Aprepitant

Drug: Placebo

Drug: 100 MK-0517 (PS80) + 2 mg midazolam

Drug: 100 mg MK-0517 (non-PS80)

Part I, Panel B

Experimental group

Description:

100 mg MK-0517 (PS80 formulation \[PS80\]) or placebo → 150 mg MK-0517 (PS80) or placebo → 125 mg aprepitant

Treatment:

Drug: 125 mg Aprepitant

Drug: Placebo

Drug: 150 mg MK-0517 (PS80)

Drug: 100 mg MK-0517 (PS80)

Part I, Panel C

Experimental group

Description:

40 mg MK-0517 (non-PS80) or placebo → 40 mg aprepitant

Treatment:

Drug: 40 mg Aprepitant

Drug: Placebo

Drug: 40 mg MK-0517 (non-PS80)

Part II

Experimental group

Description:

2 mg midazolam → 100 mg MK-0517 (PS80) + 2 mg midazolam

Treatment:

Drug: 2 mg Midazolam

Drug: 100 mg MK-0517 (PS80)

Part III, Panel 1, Treatment Sequence 1

Experimental group

Description:

125 mg aprepitant → 90 mg MK-0517 (PS80)

Treatment:

Drug: 125 mg Aprepitant

Drug: 90 mg MK-0517 (PS80)

Drug: 40 mg MK-0517 (non-PS80)

Part III, Panel 1, Treatment Sequence 2

Experimental group

Description:

40 mg MK-0517 (non-PS80) → 125 mg aprepitant

Treatment:

Drug: 125 mg Aprepitant

Drug: 40 mg MK-0517 (non-PS80)

Part III, Panel 2

Experimental group

Description:

40 mg MK-0517 (non-PS80)

Treatment:

Drug: 40 mg MK-0517 (non-PS80)

Part IV

Experimental group

Description:

40 mg MK-0517 (non-PS80 formulation)

Treatment:

Drug: 40 mg MK-0517 (non-PS80)

Part V, Treatment Sequence 1

Experimental group

Description:

125 mg aprepitant → 100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80 formulation)

Treatment:

Drug: 125 mg Aprepitant

Drug: 115 mg MK-0517 (PS80)

Drug: 100 mg MK-0517 (PS80)

Part V, Treatment Sequence 2

Experimental group

Description:

100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80) → 125 mg aprepitant

Treatment:

Drug: 125 mg Aprepitant

Drug: 115 mg MK-0517 (PS80)

Drug: 100 mg MK-0517 (PS80)

Part V, Treatment Sequence 3

Experimental group

Description:

115 mg MK-0517 (PS80) → 125 mg aprepitant → 100 mg MK-0517 (PS80)

Treatment:

Drug: 125 mg Aprepitant

Drug: 115 mg MK-0517 (PS80)

Drug: 100 mg MK-0517 (PS80)

Part V, Treatment Sequence 4

Experimental group

Description:

125 mg aprepitant → 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80)

Treatment:

Drug: 125 mg Aprepitant

Drug: 115 mg MK-0517 (PS80)

Drug: 100 mg MK-0517 (PS80)

Part V, Treatment Sequence 5

Experimental group

Description:

100 mg MK-0517 (PS80) → 125 mg aprepitant → 115 mg MK-0517 (PS80)

Treatment:

Drug: 125 mg Aprepitant

Drug: 115 mg MK-0517 (PS80)

Drug: 100 mg MK-0517 (PS80)

Part V, Treatment Sequence 6

Experimental group

Description:

115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80) → 125 mg aprepitant

Treatment:

Drug: 125 mg Aprepitant

Drug: 115 mg MK-0517 (PS80)

Drug: 100 mg MK-0517 (PS80)