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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01594749
First received: April 24, 2012
Last updated: November 2, 2015
Last verified: November 2015
  Purpose
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).

Condition Intervention Phase
Chemotherapy-Induced Nausea and Vomiting (CINV)
Drug: Fosaprepitant dimeglumine
Drug: Fosaprepitant Placebo
Drug: Dexamethasone
Drug: Ondansetron
Drug: Dexamethasone Placebo
Drug: Ondansetron Placebo
Drug: Rescue Therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    A Complete Response was defined as no vomiting and no use of rescue medication.

  • Percentage of Participants With Infusion-site Thrombophlebitis [ Time Frame: Day 1 through Day 17, inclusive ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants With Severe Infusion-site Reactions [ Time Frame: Day 1 through Day 17, inclusive ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    A Complete Response was defined as no vomiting and no use of rescue medication.

  • 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 ] [ Designated as safety issue: No ]
    A Complete Response was defined as no vomiting and no use of rescue medication.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 1015
Study Start Date: September 2012
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Fosaprepitant dimeglumine
Other Names:
  • EMEND for Injection
  • MK-0517
Drug: Dexamethasone
Other Name: Decadron
Drug: Ondansetron
Other Name: Zofran
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: Fosaprepitant Placebo Drug: Dexamethasone
Other Name: Decadron
Drug: Ondansetron
Other Name: Zofran
Drug: Rescue Therapy

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01594749

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

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01594749     History of Changes
Other Study ID Numbers: 0517-031 
Study First Received: April 24, 2012
Results First Received: August 26, 2015
Last Updated: November 2, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
NK-1 Receptor Antagonist, CINV, Emesis, MEC

Additional relevant MeSH terms:
Nausea
Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Dexamethasone acetate
Dexamethasone
Ondansetron
Fosaprepitant
Aprepitant
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antipruritics
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 30, 2016