NCT00990821

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.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
188

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jan 2005

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2005

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2005

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2006

Completed
3.8 years until next milestone

First Submitted

Initial submission to the registry

October 6, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 7, 2009

Completed
4.2 years until next milestone

Results Posted

Study results publicly available

December 12, 2013

Completed
Last Updated

August 19, 2015

Status Verified

August 1, 2015

Enrollment Period

11 months

First QC Date

October 6, 2009

Results QC Date

April 9, 2010

Last Update Submit

August 18, 2015

Conditions

Chemotherapy-Induced Nausea and VomitingPostoperative Nausea and Vomiting

Outcome Measures

Primary Outcomes (1)

  • 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

Study Arms (14)

Part I, Panel A

EXPERIMENTAL

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 midazolamDrug: 100 mg MK-0517 (non-PS80)Drug: 150 mg MK-0517 (Non-PS80)Drug: PlaceboDrug: 125 mg Aprepitant

Part I, Panel B

EXPERIMENTAL

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)Drug: 150 mg MK-0517 (PS80)Drug: PlaceboDrug: 125 mg Aprepitant

Part I, Panel C

EXPERIMENTAL

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

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

Part II

EXPERIMENTAL

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

Drug: 100 mg MK-0517 (PS80)Drug: 2 mg Midazolam

Part III, Panel 1, Treatment Sequence 1

EXPERIMENTAL

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

Drug: 90 mg MK-0517 (PS80)Drug: 40 mg MK-0517 (non-PS80)Drug: 125 mg Aprepitant

Part III, Panel 1, Treatment Sequence 2

EXPERIMENTAL

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

Drug: 40 mg MK-0517 (non-PS80)Drug: 125 mg Aprepitant

Part III, Panel 2

EXPERIMENTAL

40 mg MK-0517 (non-PS80)

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

Part IV

EXPERIMENTAL

40 mg MK-0517 (non-PS80 formulation)

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

Part V, Treatment Sequence 1

EXPERIMENTAL

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

Drug: 100 mg MK-0517 (PS80)Drug: 115 mg MK-0517 (PS80)Drug: 125 mg Aprepitant

Part V, Treatment Sequence 2

EXPERIMENTAL

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

Drug: 100 mg MK-0517 (PS80)Drug: 115 mg MK-0517 (PS80)Drug: 125 mg Aprepitant

Part V, Treatment Sequence 3

EXPERIMENTAL

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

Drug: 100 mg MK-0517 (PS80)Drug: 115 mg MK-0517 (PS80)Drug: 125 mg Aprepitant

Part V, Treatment Sequence 4

EXPERIMENTAL

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

Drug: 100 mg MK-0517 (PS80)Drug: 115 mg MK-0517 (PS80)Drug: 125 mg Aprepitant

Part V, Treatment Sequence 5

EXPERIMENTAL

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

Drug: 100 mg MK-0517 (PS80)Drug: 115 mg MK-0517 (PS80)Drug: 125 mg Aprepitant

Part V, Treatment Sequence 6

EXPERIMENTAL

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

Drug: 100 mg MK-0517 (PS80)Drug: 115 mg MK-0517 (PS80)Drug: 125 mg Aprepitant

Interventions

90 mg MK-0517 (PS80)DRUG

MK-0517 (PS80 formulation), 1 mg/mL, administered intravenous (IV) over 15 minutes

Part III, Panel 1, Treatment Sequence 1
100 mg MK-0517 (PS80)DRUG

MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes

Part I, Panel BPart IIPart V, Treatment Sequence 1Part V, Treatment Sequence 2Part V, Treatment Sequence 3Part V, Treatment Sequence 4Part V, Treatment Sequence 5Part V, Treatment Sequence 6
100 MK-0517 (PS80) + 2 mg midazolamDRUG

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.

Part I, Panel A
115 mg MK-0517 (PS80)DRUG

MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes

Part V, Treatment Sequence 1Part V, Treatment Sequence 2Part V, Treatment Sequence 3Part V, Treatment Sequence 4Part V, Treatment Sequence 5Part V, Treatment Sequence 6
150 mg MK-0517 (PS80)DRUG

MK-0517 (PS80 formulation), 1 mg/mL, administered IV over 15 minutes

Part I, Panel B
40 mg MK-0517 (non-PS80)DRUG

MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.

Part I, Panel CPart III, Panel 1, Treatment Sequence 1Part III, Panel 1, Treatment Sequence 2Part III, Panel 2Part IV
100 mg MK-0517 (non-PS80)DRUG

MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.

Part I, Panel A
150 mg MK-0517 (Non-PS80)DRUG

MK-0517 (Non-PS80) is administered as single IV dose over 30 seconds.

Part I, Panel A
PlaceboDRUG

Placebo matching MK-0517

Part I, Panel APart I, Panel BPart I, Panel C
40 mg AprepitantDRUG

Aprepitant, oral, tablet, single dose

Part I, Panel C
125 mg AprepitantDRUG

Aprepitant oral tablet, single dose

Part I, Panel APart I, Panel BPart III, Panel 1, Treatment Sequence 1Part III, Panel 1, Treatment Sequence 2Part V, Treatment Sequence 1Part V, Treatment Sequence 2Part V, Treatment Sequence 3Part V, Treatment Sequence 4Part V, Treatment Sequence 5Part V, Treatment Sequence 6
2 mg MidazolamDRUG

Midazolam oral tablet, single dose

Part II

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

VomitingPostoperative Nausea and Vomiting

Interventions

AprepitantMidazolam

Condition Hierarchy (Ancestors)

Signs and Symptoms, DigestiveSigns and SymptomsPathological Conditions, Signs and SymptomsPostoperative ComplicationsPathologic ProcessesNausea

Intervention Hierarchy (Ancestors)

MorpholinesOxazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsBenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Results Point of Contact

Title
Senior Vice President, Global Clinical Development
Organization
Merck Sharp & Dohme Corp.
ClinicalTrialsDisclosure@merck.com
1-800-672-6372

Study Officials

  • Medical Monitor

    Merck Sharp & Dohme LLC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 6, 2009

First Posted

October 7, 2009

Study Start

January 1, 2005

Primary Completion

December 1, 2005

Study Completion

January 1, 2006

Last Updated

August 19, 2015

Results First Posted

December 12, 2013

Record last verified: 2015-08