Efficacy and Safety of Fosaprepitant Dimeglumine in Preventing Chemotherapy-Induced Nausea and Vomiting (MK-0517-031)

August 2, 2018 updated by: Merck Sharp & Dohme LLC

A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Parallel-Group Study, Conducted Under In-House Blinding Conditions, to Examine the Efficacy and Safety of a Single 150 mg Dose of Intravenous Fosaprepitant Dimeglumine for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) Associated With Moderately Emetogenic Chemotherapy

This study aims to demonstrate that, when given concomitantly with a 5-hydroxytryptamine 3 (5-HT3) antagonist and a corticosteroid, a single 150 mg intravenous (IV) dose of fosaprepitant given on Day 1 is superior to the control regimen of 5-HT3 antagonist and corticosteroid only, in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1015

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Has a histologically or cytologically confirmed malignant disease
  • Is naive to moderately and highly emetogenic chemotherapy
  • Is scheduled to receive a single IV dose of one or more MEC agents on Day 1, except for the combination of anthracycline and cyclophosphamide
  • Has a predicted life expectancy of at least 4 months, and a Karnofsky score of at least 60 indicating that the participant requires occasional assistance, but is able to care for most of his/her needs.
  • Female of childbearing potential demonstrates a negative urine pregnancy test, and agrees to remain abstinent or use two acceptable forms of birth control for at least 14 days prior to study, throughout the study, and at least 1 month following last dose of study drug.

Exclusion Criteria:

  • Has vomited in the 24 hours prior to treatment Day 1
  • Has symptomatic primary or metastatic symptomatic central nervous system malignancy causing nausea and/or vomiting
  • Is scheduled to receive chemotherapy agent classified as highly emetogenic
  • Has received or will receive total body irradiation, or radiation therapy to the abdomen, pelvis, head and neck in the week prior to Treatment Days 1 through Day 6 of the Treatment Period
  • Has illness or history of illness which might confound study results or pose unwarranted risk
  • Known history of QT interval prolongation
  • Uses illicit drugs or abuses alcohol
  • Mentally incapacitated or has a significant emotional or psychiatric disorder
  • History of hypersensitivity to aprepitant, ondansetron or dexamethasone
  • Pregnant or breast-feeding
  • Has participated in a study with aprepitant or taken a non-approved (investigational) drug within the last 4 weeks
  • Has concurrent condition, such as systemic fungal infection or uncontrolled diabetes, that precludes administration of dexamethasone.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fosaprepitant Regimen
On Day 1, participants received fosaprepitant, 150 mg intravenous (IV) infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 12 mg, orally (PO) ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy, followed by 8 mg PO, 8 hours after first dose PLUS dexamethasone placebo, PO ~30 minutes prior to chemotherapy. On Days 2 and 3, participants received ondansetron placebo, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
Drug: Dexamethasone
Other Names:
  • Decadron
Drug: Ondansetron
Other Names:
  • Zofran
Drug: Fosaprepitant dimeglumine
Other Names:
  • MK-0517
  • EMEND for Injection
Drug: Dexamethasone Placebo
Drug: Ondansetron Placebo
Drug: Rescue Therapy
Active Comparator: Control Regimen
On Day 1, participants received fosaprepitant placebo, 150 mL IV infusion, ~30 minutes prior to chemotherapy PLUS dexamethasone 20 mg, PO ~30 minutes prior to chemotherapy PLUS ondansetron 16 mg total dose: 8 mg PO ~30-60 minutes prior to chemotherapy; followed by 8 mg PO, 8 hours after the first dose. On Days 2-3, participants received ondansetron 8 mg, PO every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may have been prescribed from these permitted choices: 5-HT3 antagonists (granisetron, dolasetron, tropisetron or ondansetron); phenothiazines (e.g. prochlorperazine, fluphenazine, perphenazine, thiethylperazine, or chlorpromazine); butyrophenones (e.g. haloperidol or droperidol); benzamides (e.g. metoclopramide or alizapride); benzodiazepines; corticosteroids; domperidone.
Drug: Dexamethasone
Other Names:
  • Decadron
Drug: Ondansetron
Other Names:
  • Zofran
Drug: Rescue Therapy
Drug: Fosaprepitant Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Complete Response From 25 to 120 Hours After Initiation of Moderately Emetogenic Chemotherapy (MEC)
Time Frame: 25 to 120 hours after initiation of MEC
A Complete Response was defined as no vomiting and no use of rescue medication.
25 to 120 hours after initiation of MEC
Percentage of Participants With Infusion-site Thrombophlebitis
Time Frame: Day 1 through Day 17, inclusive
The percentages of participants with infusion-site thrombophlebitis are presented. Thrombophlebitis was defined as a condition affecting a superficial vein used for an IV infusion, associated with red color, hardness upon palpation, and the presence of a tender cord and possible fever.
Day 1 through Day 17, inclusive
Percentage of Participants With Severe Infusion-site Reactions
Time Frame: Day 1 through Day 17, inclusive
The percentages of participants with severe infusion-site reactions, including severe site pain, or severe site redness (erythema) or severe site hardness (induration) are presented.
Day 1 through Day 17, inclusive

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Complete Response From 0 to 120 Hours After Initiation of MEC
Time Frame: 0 to 120 hours after initiation of MEC
A Complete Response was defined as no vomiting and no use of rescue medication.
0 to 120 hours after initiation of MEC
Percentage of Participants With Complete Response From 0 to 24 Hours After Initiation of MEC
Time Frame: 0 to 24 hours after initiation of MEC
A Complete Response was defined as no vomiting and no use of rescue medication.
0 to 24 hours after initiation of MEC
Percentage of Participants With No Vomiting From 0 to 120 Hours After Initiation of MEC
Time Frame: 0 to 120 hours after initiation of MEC
No Vomiting was defined as no emetic (vomiting) episodes, including no vomiting and no retching or dry heaves (attempts to vomit that are not productive of stomach contents), regardless of use of rescue medication.
0 to 120 hours after initiation of MEC

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 24, 2012

Primary Completion (Actual)

November 3, 2014

Study Completion (Actual)

November 3, 2014

Study Registration Dates

First Submitted

April 24, 2012

First Submitted That Met QC Criteria

May 7, 2012

First Posted (Estimate)

May 9, 2012

Study Record Updates

Last Update Posted (Actual)

September 4, 2018

Last Update Submitted That Met QC Criteria

August 2, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0517-031

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

  1. CSR Synopsis

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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