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A Study of MK-0869 (Aprepitant) and MK-0517 (Fosaprepitant) in Pediatric Participants Receiving Chemotherapy (MK-0869-134)

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ClinicalTrials.gov Identifier: NCT00818259
Recruitment Status : Terminated (Study terminated early prior to completing targeted enrollment of participants <6 months of age due to recruitment challenges.)
First Posted : January 7, 2009
Results First Posted : November 18, 2014
Last Update Posted : September 25, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE January 6, 2009
First Posted Date  ICMJE January 7, 2009
Results First Submitted Date  ICMJE October 2, 2014
Results First Posted Date  ICMJE November 18, 2014
Last Update Posted Date September 25, 2018
Actual Study Start Date  ICMJE February 5, 2009
Actual Primary Completion Date January 20, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2014)
  • Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant [ Time Frame: Up to 24 hours post fosaprepitant/aprepitant dose ]
    AUC is a measure of the amount of aprepitant in the plasma. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for pharmacokinetic (PK) assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hours (hr) post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8 and 24 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy.
  • Maximum Plasma Concentration (Cmax) for Aprepitant [ Time Frame: Up to 72 hours post fosaprepitant/aprepitant dose ]
    Cmax is a measure of the maximum amount of aprepitant in the plasma. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
  • Time to Cmax (Tmax) for Aprepitant [ Time Frame: Up to 72 hours post fosaprepitant/aprepitant dose ]
    Tmax is a measure of the amount of time after dosing to when the maximum concentration of aprepitant was achieved. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
  • Apparent Terminal Half-life (t1/2) for Aprepitant [ Time Frame: Up to 72 hours post fosaprepitant/aprepitant dose ]
    t1/2 is the amount of time from dosing until half of the aprepitant was metabolized from the body. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy; Parts II and IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
  • Cmax for Fosaprepitant [ Time Frame: Up to 72 hours post fosaprepitant dose ]
    Cmax is a measure of the maximum amount of fosaprepitant in the plasma. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
  • Tmax for Fosaprepitant [ Time Frame: Up to 72 hours post fosaprepitant dose ]
    Tmax is a measure of the amount of time after dosing to when the maximum concentration of fosaprepitant was achieved. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part V - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
  • Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 14 days after last dose of study drug (Up to 17 days) ]
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Participants were monitored for the occurrence AEs for up to 14 days after last dose of study drug.
  • Number of Participants Discontinuing Study Drug Due to an AE [ Time Frame: Day 1 up to Day 3 ]
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. The number of participants who discontinued from the study due to an AE are summarized.
Original Primary Outcome Measures  ICMJE
 (submitted: January 6, 2009)
Plasma concentration and PK parameters of aprepitant and the safety and tolerability of fosaprepitant and aprepitant based on adverse experience monitoring [ Time Frame: throughout duration of study ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2014)
Plasma Concentration and PK Parameters of Dexamethasone in Participants From Birth to 1 Year of Age [ Time Frame: Up to 24 hours post dexamethasone dose ]
Blood samples for PK assessment were to be collected at the following time points: Parts II and V - Pre-dose and 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy; Parts III and IV - Immediately after infusion of dexamethsone and 0.5, 1.5, 3, 8 and 24 hr post start of chemotherapy.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of MK-0869 (Aprepitant) and MK-0517 (Fosaprepitant) in Pediatric Participants Receiving Chemotherapy (MK-0869-134)
Official Title  ICMJE A Multicenter, Open-Label, 5-Part Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Aprepitant and Fosaprepitant Dimeglumine in Pediatric Patients Receiving Emetogenic Chemotherapy
Brief Summary This study will determine the appropriate dosing regimen of aprepitant and fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric participants from 0 months to 17 years of age.
Detailed Description Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after intravenous administration; the pharmacological effect of fosaprepitant is attributed to aprepitant. The birth to one year old cohort will be initiated in Parts III and IV upon completion of Part II (Steps A and B) in participants <6 months of age.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chemotherapy-Induced Nausea and Vomiting
Intervention  ICMJE
  • Drug: Experimental: aprepitant
    aprepitant powder for suspension, 125 mg/sachet, PO
    Other Names:
    • Emend
    • MK-0869
  • Drug: Experimental: fosaprepitant
    fosaprepitant lyophilized powder for suspension, 115 mg/vial or 150 mg/vial, IV
    Other Names:
    • Emend injection
    • Fosaprepitant Dimeglumine
    • MK-0517
  • Drug: Comparator: ondansetron
    ondansetron solution for infusion, IV, administered per local standard of care
    Other Name: Zofran
  • Drug: Ondansetron
    ondansetron solution for infusion, IV, administered per local standard of care
  • Drug: Dexamethasone
    dexamethasone solution for infusion, IV, administered per local standard of care
Study Arms  ICMJE
  • Experimental: Part IA-fosaprepitant 115 mg/aprepitant
    Day 1, fosaprepitant intravenous (IV) at a dose of 115 mg and Days 2 and 3, aprepitant 80 mg orally (PO), prior to chemotherapy for participants from 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Interventions:
    • Drug: Experimental: aprepitant
    • Drug: Experimental: fosaprepitant
    • Drug: Ondansetron
    • Drug: Dexamethasone
  • Experimental: Part IB-fosaprepitant 150 mg
    Day 1, fosaprepitant, IV at a dose of 150 mg, prior to chemotherapy for participants 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Interventions:
    • Drug: Experimental: fosaprepitant
    • Drug: Ondansetron
    • Drug: Dexamethasone
  • Experimental: Part IIA-aprepitant 80 mg equiv.
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to <12 years of age - 47 mg/m^2; 4 months to <6 months of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Interventions:
    • Drug: Experimental: aprepitant
    • Drug: Ondansetron
    • Drug: Dexamethasone
  • Experimental: Part IIB-aprepitant 125 mg equiv.
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to <12 years of age - 74 mg/m^2; 6 months to <2 years of age - 1.3 mg/kg; 4 months to <6 months of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Interventions:
    • Drug: Experimental: aprepitant
    • Drug: Ondansetron
    • Drug: Dexamethasone
  • Active Comparator: Part III-ondansetron
    Ondansetron administered IV per local standard of care on Days 1, 2, and 3 prior to chemotherapy for participants from birth to <12 years of age. The use of IV dexamethasone is optional with the exception of the birth to one year old cohort.
    Interventions:
    • Drug: Comparator: ondansetron
    • Drug: Dexamethasone
  • Experimental: Part IV-aprepitant regimen
    Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; Birth to <1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; Birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care. The use of dexamethasone IV is optional with the exception of the birth to one year old cohort.
    Interventions:
    • Drug: Experimental: aprepitant
    • Drug: Ondansetron
    • Drug: Dexamethasone
  • Experimental: Part V-fosaprepitant regimen
    Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to <12 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Interventions:
    • Drug: Experimental: fosaprepitant
    • Drug: Ondansetron
    • Drug: Dexamethasone
Publications * Kang HJ, Loftus S, Taylor A, DiCristina C, Green S, Zwaan CM. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015 Apr;16(4):385-94. doi: 10.1016/S1470-2045(15)70061-6. Epub 2015 Mar 12. Erratum in: Lancet Oncol. 2015 Sep;16(9):e427.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 4, 2014)
92
Original Estimated Enrollment  ICMJE
 (submitted: January 6, 2009)
58
Actual Study Completion Date  ICMJE January 20, 2014
Actual Primary Completion Date January 20, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Is 0 (at least 37 weeks gestation) to 17 years of age
  • Is scheduled to receive moderately to highly nausea-inducing chemotherapy or participant did not tolerate a previous chemotherapy regimen that is planned to be repeated
  • Is expected to receive ondansetron
  • Female participants who have begun menstruating must have a negative pregnancy test
  • Weighs ≥3.0 kg if <6 months of age, ≥6.0 kg if >6 months of age, and ≥7.5 kg if > 2 years of age
  • Has a pre-existing venous catheter

Exclusion Criteria:

  • Uses any illicit drugs or abuses alcohol
  • Is pregnant or breast feeding
  • Has a symptomatic central nervous system (CNS) tumor
  • Has an infection or other uncontrolled disease other than cancer
  • Has known history of heart QT wave prolongation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Brazil,   Canada,   Colombia,   France,   Germany,   Hungary,   Israel,   Mexico,   Norway,   Peru,   Poland,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT00818259
Other Study ID Numbers  ICMJE 0869-134
2009_501 ( Other Identifier: Telerx Study Identifier )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP