search
Back to results

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)

Primary Purpose

Chemotherapy-induced Nausea and Vomiting

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Fosaprepitant
Fosaprepitant Placebo
Ondansetron
5-hydroxytryptamine 3 antagonist
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chemotherapy-induced Nausea and Vomiting

Eligibility Criteria

undefined - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Placebo Comparator

    Experimental

    Experimental

    Arm Label

    Fosaprepitant 5 mg/kg-Cycle 1

    Fosaprepitant 3 mg/kg-Cycle 1

    Fosaprepitant 1.2 mg/kg-Cycle 1

    Fosaprepitant 0.4 mg/kg-Cycle 1

    Placebo Control-Cycle 1

    Fosaprepitant 5 mg/kg-Cycles 2-6

    Fosaprepitant 3 mg/kg-Cycles 2-6

    Arm Description

    Participants were administered intravenous (IV) fosaprepitant at the following weight-adjusted doses: participants 4 months to <12 years old were administered 5 mg/kg (not to exceed 150 mg); participants 1 to <4 months old were administered 2.5 mg/kg; participants 0 to <1 month old were administered 1.25 mg/kg. Participants were also administered IV 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), with or without dexamethasone.

    Participants 12 to 17 years old were administered 150 mg IV fosaprepitant. Participants 2 to <12 years old were administered a weight-adjusted dose of 3 mg/kg (not to exceed 150 mg). Participants were also administered IV 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), with or without dexamethasone.

    Participants 12 to 17 years old were administered 60 mg IV fosaprepitant. Participants 2 to <12 years old were administered a weight-adjusted dose of 1.2 mg/kg (not to exceed 60 mg). Participants were also administered IV 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), with or without dexamethasone.

    Participants 12 to 17 years old were administered 20 mg IV fosaprepitant. Participants 2 to <12 years old were administered a weight-adjusted dose of 0.4 mg/kg (not to exceed 20 mg). Participants were also administered IV 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), with or without dexamethasone.

    Participants were administered IV normal saline at volume to match age and weight specific doses of fosaprepitant. Participants were also administered IV 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), with or without dexamethasone.

    For optional Cycles 2-6, participants from the 5 mg/kg fosaprepitant arm in Cycle 1 were administered fosaprepitant 5 mg/kg IV (or age-adjusted equivalent). For Cycle 2, fosaprepitant was administered IV plus ondansetron with or without dexamethasone. For Cycles 3-6, fosaprepitant was administered IV plus a 5- hydroxytryptamine 3 (5-HT3) antagonist with or without dexamethasone. Participants 1 year or less were required to receive ondansetron in all cycles as the 5-HT3 antagonist.

    For optional Cycles 2-6, participants from Cycle 1 fosaprepitant arms (3, 1.2, or 0.4 mg/kg) or Cycle 1 control arm were administered fosaprepitant 3 mg/kg IV (or age-adjusted equivalent). For Cycle 2, fosaprepitant was administered IV plus ondansetron with or without dexamethasone. For Cycles 3-6, fosaprepitant was administered IV plus a 5-HT3 antagonist with or without dexamethasone.

    Outcomes

    Primary Outcome Measures

    Maximum Concentration (Cmax) of Aprepitant in Participants 0 to <2 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time to Maximum Concentration (Tmax) of Aprepitant in Participants 0 to <2 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC 0-∞) in Participants 0 to <2 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Area Under the Concentration-time Curve of Aprepitant From Time 0 to 24 Hours (AUC 0-24hr) in Participants 0 to <2 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Apparent Terminal Half-life (t1/2) of Aprepitant in Participants 0 to <2 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Concentration of Aprepitant After 24 Hours (C24hr) in Participants 0 to <2 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
    Concentration of Aprepitant After 48 Hours (C48hr) in Participants 0 to <2 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
    Apparent Total Body Clearance (CL/F) of Aprepitant in Participants 0 to <2 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Cmax of Aprepitant in Participants 2 to <6 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Tmax of Aprepitant in Participants 2 to <6 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    AUC 0-∞ of Aprepitant in Participants 2 to <6 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    AUC 0-24hr of Aprepitant in Participants 2 to <6 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    t1/2 of Aprepitant in Participants 2 to <6 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    C24hr of Aprepitant in Participants 2 to <6 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
    C48hr of Aprepitant in Participants 2 to <6 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
    CL/F of Aprepitant in Participants 2 to <6 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Cmax of Aprepitant in Participants 6 to <12 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Tmax of Aprepitant in Participants 6 to <12 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    AUC 0-∞ of Aprepitant in Participants 6 to <12 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    AUC 0-24hr of Aprepitant in Participants 6 to <12 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    t1/2 of Aprepitant in Participants 6 to <12 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    C24hr of Aprepitant in Participants 6 to <12 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
    C48hr of Aprepitant in Participants 6 to <12 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
    CL/F of Aprepitant in Participants 6 to <12 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Cmax of Aprepitant in Participants 12 to 17 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Tmax of Aprepitant in Participants 12 to 17 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    AUC 0-∞ of Aprepitant in Participants 12 to 17 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    AUC 0-24hr of Aprepitant in Participants 12 to 17 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    t1/2 of Aprepitant in Participants 12 to 17 Years of Age Hours
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    C24hr of Aprepitant in Participants 12 to 17 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
    C48hr of Aprepitant in Participants 12 to 17 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
    CL/F of Aprepitant in Participants 12 to 17 Years of Age
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1
    AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
    Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycles 2-6
    AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.

    Secondary Outcome Measures

    Full Information

    First Posted
    September 28, 2012
    Last Updated
    June 14, 2019
    Sponsor
    Merck Sharp & Dohme LLC
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT01697579
    Brief Title
    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)
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    December 13, 2012 (Actual)
    Primary Completion Date
    November 21, 2016 (Actual)
    Study Completion Date
    November 21, 2016 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study was 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 completed the randomized Cycle 1 could elect to receive open-label fosaprepitant during optional Cycles 2-6.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chemotherapy-induced Nausea and Vomiting

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    240 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Fosaprepitant 5 mg/kg-Cycle 1
    Arm Type
    Experimental
    Arm Description
    Participants were administered intravenous (IV) fosaprepitant at the following weight-adjusted doses: participants 4 months to <12 years old were administered 5 mg/kg (not to exceed 150 mg); participants 1 to <4 months old were administered 2.5 mg/kg; participants 0 to <1 month old were administered 1.25 mg/kg. Participants were also administered IV 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), with or without dexamethasone.
    Arm Title
    Fosaprepitant 3 mg/kg-Cycle 1
    Arm Type
    Experimental
    Arm Description
    Participants 12 to 17 years old were administered 150 mg IV fosaprepitant. Participants 2 to <12 years old were administered a weight-adjusted dose of 3 mg/kg (not to exceed 150 mg). Participants were also administered IV 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), with or without dexamethasone.
    Arm Title
    Fosaprepitant 1.2 mg/kg-Cycle 1
    Arm Type
    Experimental
    Arm Description
    Participants 12 to 17 years old were administered 60 mg IV fosaprepitant. Participants 2 to <12 years old were administered a weight-adjusted dose of 1.2 mg/kg (not to exceed 60 mg). Participants were also administered IV 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), with or without dexamethasone.
    Arm Title
    Fosaprepitant 0.4 mg/kg-Cycle 1
    Arm Type
    Experimental
    Arm Description
    Participants 12 to 17 years old were administered 20 mg IV fosaprepitant. Participants 2 to <12 years old were administered a weight-adjusted dose of 0.4 mg/kg (not to exceed 20 mg). Participants were also administered IV 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), with or without dexamethasone.
    Arm Title
    Placebo Control-Cycle 1
    Arm Type
    Placebo Comparator
    Arm Description
    Participants were administered IV normal saline at volume to match age and weight specific doses of fosaprepitant. Participants were also administered IV 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), with or without dexamethasone.
    Arm Title
    Fosaprepitant 5 mg/kg-Cycles 2-6
    Arm Type
    Experimental
    Arm Description
    For optional Cycles 2-6, participants from the 5 mg/kg fosaprepitant arm in Cycle 1 were administered fosaprepitant 5 mg/kg IV (or age-adjusted equivalent). For Cycle 2, fosaprepitant was administered IV plus ondansetron with or without dexamethasone. For Cycles 3-6, fosaprepitant was administered IV plus a 5- hydroxytryptamine 3 (5-HT3) antagonist with or without dexamethasone. Participants 1 year or less were required to receive ondansetron in all cycles as the 5-HT3 antagonist.
    Arm Title
    Fosaprepitant 3 mg/kg-Cycles 2-6
    Arm Type
    Experimental
    Arm Description
    For optional Cycles 2-6, participants from Cycle 1 fosaprepitant arms (3, 1.2, or 0.4 mg/kg) or Cycle 1 control arm were administered fosaprepitant 3 mg/kg IV (or age-adjusted equivalent). For Cycle 2, fosaprepitant was administered IV plus ondansetron with or without dexamethasone. For Cycles 3-6, fosaprepitant was administered IV plus a 5-HT3 antagonist with or without dexamethasone.
    Intervention Type
    Drug
    Intervention Name(s)
    Fosaprepitant
    Other Intervention Name(s)
    Fosaprepitant dimeglumine, MK-0517, EMEND® for Injection
    Intervention Description
    Administered intravenously (IV) as a single dose
    Intervention Type
    Drug
    Intervention Name(s)
    Fosaprepitant Placebo
    Intervention Description
    Administered IV as a single dose
    Intervention Type
    Drug
    Intervention Name(s)
    Ondansetron
    Other Intervention Name(s)
    Ondansetron hydrochloride, Zofran® Injection
    Intervention Description
    Administered IV according to local labeling and/or local standard of care
    Intervention Type
    Drug
    Intervention Name(s)
    5-hydroxytryptamine 3 antagonist
    Other Intervention Name(s)
    5-HT3
    Intervention Description
    Administered IV according to local labeling and/or local standard of care
    Primary Outcome Measure Information:
    Title
    Maximum Concentration (Cmax) of Aprepitant in Participants 0 to <2 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Time to Maximum Concentration (Tmax) of Aprepitant in Participants 0 to <2 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC 0-∞) in Participants 0 to <2 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Area Under the Concentration-time Curve of Aprepitant From Time 0 to 24 Hours (AUC 0-24hr) in Participants 0 to <2 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Apparent Terminal Half-life (t1/2) of Aprepitant in Participants 0 to <2 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Concentration of Aprepitant After 24 Hours (C24hr) in Participants 0 to <2 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
    Time Frame
    Approximately 24 hours (from 23 to 25 hours) post-infusion
    Title
    Concentration of Aprepitant After 48 Hours (C48hr) in Participants 0 to <2 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
    Time Frame
    Approximately 48 hours (from 46 to 50 hours) post-infusion
    Title
    Apparent Total Body Clearance (CL/F) of Aprepitant in Participants 0 to <2 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Cmax of Aprepitant in Participants 2 to <6 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Tmax of Aprepitant in Participants 2 to <6 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    AUC 0-∞ of Aprepitant in Participants 2 to <6 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    AUC 0-24hr of Aprepitant in Participants 2 to <6 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    t1/2 of Aprepitant in Participants 2 to <6 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    C24hr of Aprepitant in Participants 2 to <6 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
    Time Frame
    Approximately 24 hours (from 23 to 25 hours) post-infusion
    Title
    C48hr of Aprepitant in Participants 2 to <6 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
    Time Frame
    Approximately 48 hours (from 46 to 50 hours) post-infusion
    Title
    CL/F of Aprepitant in Participants 2 to <6 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Cmax of Aprepitant in Participants 6 to <12 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Tmax of Aprepitant in Participants 6 to <12 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    AUC 0-∞ of Aprepitant in Participants 6 to <12 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    AUC 0-24hr of Aprepitant in Participants 6 to <12 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    t1/2 of Aprepitant in Participants 6 to <12 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    C24hr of Aprepitant in Participants 6 to <12 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
    Time Frame
    Approximately 24 hours (from 23 to 25 hours) post-infusion
    Title
    C48hr of Aprepitant in Participants 6 to <12 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
    Time Frame
    Approximately 48 hours (from 46 to 50 hours) post-infusion
    Title
    CL/F of Aprepitant in Participants 6 to <12 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Cmax of Aprepitant in Participants 12 to 17 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Tmax of Aprepitant in Participants 12 to 17 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    AUC 0-∞ of Aprepitant in Participants 12 to 17 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    AUC 0-24hr of Aprepitant in Participants 12 to 17 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    t1/2 of Aprepitant in Participants 12 to 17 Years of Age Hours
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    C24hr of Aprepitant in Participants 12 to 17 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels in the time frame of 23 to 25 hours post-infusion.
    Time Frame
    Approximately 24 hours (from 23 to 25 hours) post-infusion
    Title
    C48hr of Aprepitant in Participants 12 to 17 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels in the time frame of 46 to 50 hours post-infusion. The C48hr was only planned to be measured in the 5 mg/mL dose for each age group.
    Time Frame
    Approximately 48 hours (from 46 to 50 hours) post-infusion
    Title
    CL/F of Aprepitant in Participants 12 to 17 Years of Age
    Description
    Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, fosaprepitant cannot be assessed directly. The pharmacokinetics for each fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.
    Time Frame
    Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion
    Title
    Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1
    Description
    AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
    Time Frame
    Up to 14 days postdose in Cycle 1
    Title
    Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycles 2-6
    Description
    AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
    Time Frame
    Up to 14 days postdose for each cycle (Cycles 2-6)

    10. Eligibility

    Sex
    All
    Maximum Age & Unit of Time
    17 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    30900392
    Citation
    Mora J, Valero M, DiCristina C, Jin M, Chain A, Bickham K. Pharmacokinetics/pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients. Pediatr Blood Cancer. 2019 Jun;66(6):e27690. doi: 10.1002/pbc.27690. Epub 2019 Mar 21.
    Results Reference
    result

    Learn more about this trial

    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)

    We'll reach out to this number within 24 hrs