We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Fosaprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Children (MK-0517-029)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01697579
First Posted: October 2, 2012
Last Update Posted: October 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
  Purpose
The purpose of this study is to determine the appropriate dosing regimen of fosaprepitant, when administered with ondansetron (with or without dexamethasone), for the prevention of CINV in children from birth to <17 years of age. Fosaprepitant is a prodrug to aprepitant. All participants who complete the randomized Cycle 1 may elect to receive open-label fosaprepitant during optional Cycles 2-6.

Condition Intervention Phase
Chemotherapy-induced Nausea and Vomiting Drug: Fosaprepitant 150 mg Drug: Fosaprepitant 60 mg Drug: Fosaprepitant 20 mg Drug: Placebo Fosaprepitant Drug: Ondansetron Drug: Fosaprepitant 5 mg/kg Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIb, Partially-Blinded, Randomized, Active Comparator-Controlled Study to Evaluate the Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Fosaprepitant in Pediatric Patients for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) Associated With Emetogenic Chemotherapy Sub-title: Open-Label Cohort to Further Evaluate the Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Fosaprepitant in Pediatric Patients Birth to <12 Years Old

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Aprepitant Area Under the Curve from 0 to infinity (∞) hours (AUC 0-∞) [ Time Frame: Up to 48 hours postdose ]
  • Aprepitant Maximum Concentration (Cmax) [ Time Frame: Up to 48 hours postdose ]
  • Time to Aprepitant Cmax (Tmax) [ Time Frame: Up to 48 hours postdose ]
  • Aprepitant Terminal Phase Half-Life (t1/2) [ Time Frame: Up to 48 hours postdose ]
  • Aprepitant Apparent Total Body Clearance (CL/F) [ Time Frame: Up to 48 hours postdose ]
  • Percentage of Participants Who Experience At Least One Adverse Event [ Time Frame: Up to 14 days postdose ]
  • Aprepitant AUC from 0 to 24 hours (AUC 0-24) [ Time Frame: Up to 24 hours postdose ]
  • Aprepitant Concentration at 24 hours (C24) [ Time Frame: Up to 24 hours postdose ]
  • Aprepitant Concentration at 48 hours (C48) [ Time Frame: Up to 48 hours postdose ]

Enrollment: 241
Actual Study Start Date: December 13, 2012
Study Completion Date: November 21, 2016
Primary Completion Date: November 21, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fosaprepitant 150 mg Adult Equivalent Dose
Cycle 1: Fosaprepitant 150 mg (or age-adjusted equivalent for children <12 years of age), administered intravenously (IV) plus ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), administered IV. Optional Cycles 2-6: Fosaprepitant 150 mg (or age-adjusted equivalent for children <12 years of age), administered IV plus a 5-hydroxytryptamine 3 (5-HT3) antagonist. (Dosing closed by Amendment 04)
Drug: Fosaprepitant 150 mg
Administered IV as a single dose
Other Names:
  • Fosaprepitant dimeglumine
  • MK-0517
  • EMEND® for Injection
Drug: Ondansetron
Administered IV
Other Names:
  • Ondansetron hydrochloride
  • Zofran® Injection
Experimental: Fosaprepitant 60 mg Adult Equivalent Dose
Cycle 1: Fosaprepitant 60 mg (or age-adjusted equivalent for children <12 years of age), administered IV plus ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), administered IV. Optional Cycles 2-6: Fosaprepitant 150 mg (or age-adjusted equivalent for children <12 years of age), administered IV plus a 5-HT3 antagonist. (Dosing closed by Amendment 04)
Drug: Fosaprepitant 60 mg
Administered IV as a single dose
Other Names:
  • Fosaprepitant dimeglumine
  • MK-0517
  • EMEND® for Injection
Drug: Ondansetron
Administered IV
Other Names:
  • Ondansetron hydrochloride
  • Zofran® Injection
Experimental: Fosaprepitant 20 mg Adult Equivalent Dose
Cycle 1: Fosaprepitant 20 mg (or age-adjusted equivalent for children <12 years of age), administered IV plus ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), administered IV. Optional Cycles 2-6: Fosaprepitant 150 mg (or age-adjusted equivalent for children <12 years of age), administered IV plus a 5-HT3 antagonist. (Dosing closed by Amendment 04)
Drug: Fosaprepitant 20 mg
Administered IV as a single dose
Other Names:
  • Fosaprepitant dimeglumine
  • MK-0517
  • EMEND® for Injection
Drug: Ondansetron
Administered IV
Other Names:
  • Ondansetron hydrochloride
  • Zofran® Injection
Active Comparator: Ondansetron
Cycle 1: Matching Placebo to fosaprepitant, administered IV plus ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), administered IV. Optional Cycles 2-6: Fosaprepitant 150 mg (or weight-adjusted equivalent for children <12 years of age), administered IV plus a 5-HT3 antagonist. (Dosing closed by Amendment 04)
Drug: Placebo Fosaprepitant
Administered IV as a single dose
Drug: Ondansetron
Administered IV
Other Names:
  • Ondansetron hydrochloride
  • Zofran® Injection
Experimental: Fosaprepitant 5 mg/kg Age-based Equivalent
Cycle 1: Fosaprepitant 5 mg/kg (or age-adjusted equivalent for children <4 months of age; not to exceed 150 mg), administered IV plus ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), administered IV. Optional Cycles 2-6: Fosaprepitant 5 mg/kg mg (or age-adjusted equivalent for children <4 months of age), administered IV plus a 5-HT3 antagonist. (Dosing initiated by Amendment 04)
Drug: Fosaprepitant 5 mg/kg
Administered IV as a single dose
Other Names:
  • Fosaprepitant dimeglumine
  • MK-0517
  • EMEND® for Injection

Detailed Description:
Under Amendment 01, 0517-029 enrolled participants in the following age cohorts: 2-<6, 6-<12 and 12-17 years old. The study was randomized, partially-blinded, with parallel group assignment. Participants were randomized to one of three fosaprepitant doses or the control group. (Amendment 02 and Amendment 03 were country-specific amendments in Brazil that were required as per local regulations with no change in study design.) Under Amendment 04, the 12-17 year old cohort was closed since that cohort fully enrolled. An additional fosaprepitant dose was added and all participants were allocated to this one treatment group. Amendment 04 was open-label and enrolled participants in the following age cohorts: 0-<2, 2-<6 and 6-<12 years old.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is 0 months (at least 37 weeks gestation) to <18 years of age
  • Scheduled to receive chemotherapeutic agent(s) associated with moderate, high, or very high risk of emetogenicity for no more than 5 consecutive days for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting
  • Expected to receive ondansetron as part of antiemetic regimen (Cycle 1); Expected to receive a 5-HT3 antagonist as part of antiemetic regimen (Cycles 2-6)
  • If female and has begun menstruating, must have a negative pregnancy test prior to study participation and agree to remain abstinent or use a barrier form of contraception
  • Predicted life expectancy of ≥3 months
  • Pre-existing functioning central venous catheter
  • Weight ≥3rd percentile for age and gender (and ≥3.0 kg)

Exclusion Criteria:

  • Vomited in the 24 hours prior study drug administration (Cycle 1)
  • Current user of any illicit drugs (including marijuana) or current evidence of alcohol abuse
  • Scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy
  • Received or will receive radiation therapy to the abdomen or pelvis in the week prior to study drug administration and/or during the course of the study
  • Pregnant or breast feeding
  • Allergic to fosaprepitant, aprepitant, ondansetron, or any other 5-HT3 antagonist
  • Has a symptomatic central nervous system (CNS) tumor causing nausea and/or vomiting
  • Has an active infection, congestive heart failure, slow heart rate, or other uncontrolled disease other than cancer
  • Mentally incapacitated or has a significant emotional or psychiatric disorder
  • Known history of QT prolongation or is taking any medication known to lead to QT prolongation
  • Taking other excluded medications
  • Participated in any previous study of aprepitant or fosaprepitant, or taken an investigational drug within 4 weeks prior to study participation
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01697579


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

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01697579     History of Changes
Other Study ID Numbers: 0517-029
2012-002340-24 ( EudraCT Number )
First Submitted: September 28, 2012
First Posted: October 2, 2012
Last Update Posted: October 19, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php


Additional relevant MeSH terms:
Nausea
Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Ondansetron
Fosaprepitant
Aprepitant
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipruritics
Dermatologic Agents
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Anxiety Agents
Neurokinin-1 Receptor Antagonists