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

Postoperative Nausea and Vomiting Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00990821
• Other study ID #: 0517-012
• Secondary ID: MK-0517-012
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2009
• Last updated: August 18, 2015
• Start date: January 2005
• Est. completion date: January 2006

Study information

• Verified date: August 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: January 2006
• Est. primary completion date: December 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chemotherapy-Induced Nausea and Vomiting
• Nausea
• Postoperative Nausea and Vomiting
• Vomiting

Intervention

Drug:
• 90 mg MK-0517 (PS80)
MK-0517 (PS80 formulation), 1 mg/mL, administered intravenous (IV) over 15 minutes
• 100 mg MK-0517 (PS80)
MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes
• 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.
• 115 mg MK-0517 (PS80)
MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes
• 150 mg MK-0517 (PS80)
MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes
• 40 mg MK-0517 (non-PS80)
MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.
• 100 mg MK-0517 (non-PS80)
MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.
• 150 mg MK-0517 (Non-PS80)
MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.
• Placebo
Placebo matching MK-0517
• 40 mg Aprepitant
Aprepitant, oral, tablet, single dose
• 125 mg Aprepitant
Aprepitant oral tablet, single dose
• 2 mg Midazolam
Midazolam oral tablet, single dose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No