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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00990821
First received: October 6, 2009
Last updated: April 29, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Chemotherapy-Induced Nausea and Vomiting
Postoperative Nausea and Vomiting
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
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Area Under the Plasma-Time Curve (AUC[0 to Infinity]) for Aprepitant and MK-0517 for Study Part V [ Time Frame: Up to 72 Hours Post Dose ] [ Designated as safety issue: No ]
    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.


Enrollment: 188
Study Start Date: January 2005
Study Completion Date: January 2006
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: 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
Drug: Placebo
Placebo matching MK-0517
Drug: 125 mg Aprepitant
Aprepitant oral tablet, single dose
Experimental: Part I, Panel C
40 mg MK-0517 (non-PS80) or placebo → 40 mg aprepitant
Drug: 40 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: 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: 90 mg MK-0517 (PS80)
MK-0517 (PS80 formulation), 1 mg/mL, administered intravenous (IV) over 15 minutes
Drug: 40 mg MK-0517 (non-PS80)
MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.
Drug: 125 mg Aprepitant
Aprepitant oral tablet, single dose
Experimental: Part III, Panel 1, Treatment Sequence 2
40 mg MK-0517 (non-PS80) → 125 mg aprepitant
Drug: 40 mg MK-0517 (non-PS80)
MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.
Drug: 125 mg Aprepitant
Aprepitant oral tablet, single dose
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: 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
Drug: 125 mg Aprepitant
Aprepitant oral tablet, single dose
Experimental: Part V, Treatment Sequence 2
100 mg MK-0517 (PS80) → 115 mg MK-0517 (PS80) → 125 mg aprepitant
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
Drug: 125 mg Aprepitant
Aprepitant oral tablet, single dose
Experimental: Part V, Treatment Sequence 3
115 mg MK-0517 (PS80) → 125 mg aprepitant → 100 mg MK-0517 (PS80)
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
Drug: 125 mg Aprepitant
Aprepitant oral tablet, single dose
Experimental: Part V, Treatment Sequence 4
125 mg aprepitant → 115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80)
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
Drug: 125 mg Aprepitant
Aprepitant oral tablet, single dose
Experimental: Part V, Treatment Sequence 5
100 mg MK-0517 (PS80) → 125 mg aprepitant → 115 mg MK-0517 (PS80)
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
Drug: 125 mg Aprepitant
Aprepitant oral tablet, single dose
Experimental: Part V, Treatment Sequence 6
115 mg MK-0517 (PS80) → 100 mg MK-0517 (PS80) → 125 mg aprepitant
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
Drug: 125 mg Aprepitant
Aprepitant oral tablet, single dose

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990821

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00990821     History of Changes
Other Study ID Numbers: 0517-012, MK-0517-012
Study First Received: October 6, 2009
Results First Received: April 9, 2010
Last Updated: April 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Nausea
Vomiting
Postoperative Nausea and Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Postoperative Complications
Pathologic Processes
Midazolam
Aprepitant
Fosaprepitant
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014