Efficacy and Safety of Fosaprepitant Dimeglumine in Preventing Chemotherapy-Induced Nausea and Vomiting (MK-0517-031 AM4) - Full Text View

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 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	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: Treatment
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:

MedlinePlus related topics: Nausea and Vomiting Steroids

Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone sodium phosphate Ondansetron hydrochloride Ondansetron Aprepitant Fosaprepitant Fosaprepitant dimeglumine

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Number of participants with Complete Response from 25 to 120 hours after initiation of MEC. [ Time Frame: 25 to 120 hours ] [ Designated as safety issue: No ]
Number of participants with infusion-site thrombophlebitis [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]
Number of participants with severe infusion-site reactions, including site pain, or site redness (erythema) or site hardness (induration) [ Time Frame: Day 1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Number of participants with Complete Response from 0 to 120 hours after initiation of MEC [ Time Frame: 0 to 120 hours ] [ Designated as safety issue: No ]
Number of participants with Complete Response from 0 to 24 hours after initiation of MEC [ Time Frame: 0 to 24 hours ] [ Designated as safety issue: No ]
Number of participants with No Vomiting from 0 to 120 hours after initiation of MEC [ Time Frame: 0 to 120 hours ] [ Designated as safety issue: No ]

Estimated Enrollment:	990
Study Start Date:	September 2012
Estimated Study Completion Date:	January 2014
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Fosaprepitant IV Fosaprepitant dimeglumine: Single 150 mg dose intravenously, approximately (~) 30 minutes prior to chemotherapy on Day 1 Dexamethasone 12 mg: orally (po) on Day 1, ~30 minutes prior to chemotherapy Ondansetron 16 mg: 8 mg po, ~30-60 minutes prior to chemotherapy, followed by 8 mg po, 8 hours after first dose for a total dose of 16 mg on Day 1. Dexamethasone Placebo: po, ~30 minutes prior to chemotherapy on Day 1 Ondansetron Placebo: po every 12 hours, on Days 2 and 3 Rescue Therapy: For established cases of nausea or vomiting, medications may be prescribed at the investigator's discretion from the following list of 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 Therapy Fosaprepitant Placebo: Fosaprepitant placebo in the form of 150 mL of 0.9% normal saline intravenously, ~30 minutes hour prior to chemotherapy on Day 1 Dexamethasone 20 mg: po, ~30 minutes prior to chemotherapy on Day 1 Ondansetron 16 mg: Day 1 - 8 mg orally, ~30-60 minutes prior to chemotherapy; followed by 8 mg orally, 8 hours after the first dose for a total daily dose of 16 mg. Days 2-3 - 8 mg orally every 12 hours. Rescue Therapy: For established cases of nausea or vomiting, medications may be prescribed at the investigator's discretion from the following list of 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

Arms

Assigned Interventions

Experimental: Fosaprepitant IV

Fosaprepitant dimeglumine: Single 150 mg dose intravenously, approximately (~) 30 minutes prior to chemotherapy on Day 1

Dexamethasone 12 mg: orally (po) on Day 1, ~30 minutes prior to chemotherapy

Ondansetron 16 mg: 8 mg po, ~30-60 minutes prior to chemotherapy, followed by 8 mg po, 8 hours after first dose for a total dose of 16 mg on Day 1.

Dexamethasone Placebo: po, ~30 minutes prior to chemotherapy on Day 1

Ondansetron Placebo: po every 12 hours, on Days 2 and 3

Rescue Therapy: For established cases of nausea or vomiting, medications may be prescribed at the investigator's discretion from the following list of 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 Therapy

Fosaprepitant Placebo: Fosaprepitant placebo in the form of 150 mL of 0.9% normal saline intravenously, ~30 minutes hour prior to chemotherapy on Day 1

Dexamethasone 20 mg: po, ~30 minutes prior to chemotherapy on Day 1

Ondansetron 16 mg: Day 1 - 8 mg orally, ~30-60 minutes prior to chemotherapy; followed by 8 mg orally, 8 hours after the first dose for a total daily dose of 16 mg. Days 2-3 - 8 mg orally every 12 hours.

Rescue Therapy: For established cases of nausea or vomiting, medications may be prescribed at the investigator's discretion from the following list of 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
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 (AC MEC)
Has a predicted life expectancy of at least 4 months, and a Karnofsky score of at least 60 indicating that the subject 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 medication

Exclusion Criteria:

Has vomited in the 24 hours prior to treatment Day 1
Has symptomatic primary or metastatic symptomatic central nervous system (CNS) malignancy causing nausea and/or vomiting
Is scheduled to receive chemotherapy agent classified as highly emetogenic
Has received or will receive total body irradiation (TBI), 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 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
Takes other excluded medication

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01594749

Contacts

Contact: Toll Free Number

1-888-577-8839

Show 41 Study Locations

Sponsors and Collaborators

Merck

More Information

No publications provided

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT01594749 History of Changes
Other Study ID Numbers:	0517-031
Study First Received:	April 24, 2012
Last Updated:	May 13, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Nausea
Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Dexamethasone acetate
Dexamethasone
Ondansetron
Aprepitant
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
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

ClinicalTrials.gov processed this record on May 19, 2013