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 is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01697579
First received: September 28, 2012
Last updated: May 6, 2016
Last verified: May 2016
  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 (changed to birth to <12 years of age in Amendment 04). 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: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
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

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 ∞ hours (AUC 0-∞) [ Time Frame: Up to 48 hours postdose ] [ Designated as safety issue: No ]
  • Aprepitant Maximum Concentration (Cmax) [ Time Frame: Up to 48 hours postdose ] [ Designated as safety issue: No ]
  • Time to Aprepitant Cmax (Tmax) [ Time Frame: Up to 48 hours postdose ] [ Designated as safety issue: No ]
  • Aprepitant Terminal Phase Half-Life (t1/2) [ Time Frame: Up to 48 hours postdose ] [ Designated as safety issue: No ]
  • Aprepitant Apparent Total Body Clearance (CL/F) [ Time Frame: Up to 48 hours postdose ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Experience At Least One Adverse Event [ Time Frame: Up to 14 days postdose ] [ Designated as safety issue: Yes ]
  • Aprepitant AUC from 0 to 24 hours (AUC 0-24) [ Time Frame: Up to 24 hours postdose ] [ Designated as safety issue: No ]
  • Aprepitant Concentration at 24 hours (C24) [ Time Frame: Up to 24 hours postdose ] [ Designated as safety issue: No ]
  • Aprepitant Concentration at 48 hours (C48) [ Time Frame: Up to 48 hours postdose ] [ Designated as safety issue: No ]

Estimated Enrollment: 227
Study Start Date: December 2012
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (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:
As a result of Protocol Amendment 04, only one dose equivalent of open-label fosaprepitant (5 mg/kg for participants <12 years to <=4 months of age, 2.5 mg/kg for participants <4 months to 1 month of age and 1.25 mg/kg for participants <1 month to 0 months of age) will be evaluated in children aged birth to <12 years to allow for further pharmacokinetic, pharmacodynamic, safety and tolerability assessments of fosaprepitant in participants from birth to <12 years of age.
  Eligibility

Ages Eligible for Study:   up to 11 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is 0 months (at least 37 weeks gestation) to <18 years of age (Amendment 04: Changed age eligibility criterion to: birth to <12 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
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: 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 
Study First Received: September 28, 2012
Last Updated: May 6, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 25, 2016