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

This study has been terminated.
(Study terminated early prior to completing targeted enrollment of participants <6 months of age due to recruitment challenges.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00818259
First received: January 6, 2009
Last updated: November 14, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Chemotherapy-Induced Nausea and Vomiting
Drug: Experimental: aprepitant
Drug: Experimental: fosaprepitant
Drug: Comparator: ondansetron
Drug: Ondansetron
Drug: Dexamethasone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 92
Study Start Date: February 2009
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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, IV
Other Names:
  • Emend injection
  • Fosaprepitant Dimeglumine
  • MK-0517
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
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.
Drug: Experimental: fosaprepitant
fosaprepitant lyophilized powder for suspension, 115 mg/vial, IV
Other Names:
  • Emend injection
  • Fosaprepitant Dimeglumine
  • MK-0517
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
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.
Drug: Experimental: aprepitant
aprepitant powder for suspension, 125 mg/sachet, PO
Other Names:
  • Emend
  • MK-0869
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
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.
Drug: Experimental: aprepitant
aprepitant powder for suspension, 125 mg/sachet, PO
Other Names:
  • Emend
  • MK-0869
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
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.
Drug: Comparator: ondansetron
ondansetron solution for infusion, IV, administered per local standard of care
Other Name: Zofran
Drug: Dexamethasone
dexamethasone solution for infusion, IV, administered per local standard of care
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.
Drug: Experimental: aprepitant
aprepitant powder for suspension, 125 mg/sachet, PO
Other Names:
  • Emend
  • MK-0869
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
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.
Drug: Experimental: fosaprepitant
fosaprepitant lyophilized powder for suspension, 115 mg/vial, IV
Other Names:
  • Emend injection
  • Fosaprepitant Dimeglumine
  • MK-0517
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

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.

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00818259

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

Additional Information:
No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00818259     History of Changes
Other Study ID Numbers: 0869-134, 2009_501
Study First Received: January 6, 2009
Results First Received: October 2, 2014
Last Updated: November 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Aprepitant
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Fosaprepitant
Ondansetron
Anti-Anxiety Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antipruritics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dermatologic Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014