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

Chemotherapy-Induced Nausea and Vomiting Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00818259
• Other study ID #: 0869-134
• Secondary ID: 2009_501
• Status: Terminated
• Phase: Phase 1
• Start date: February 5, 2009
• Est. completion date: January 20, 2014

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 92
• Est. completion date: January 20, 2014
• Est. primary completion date: January 20, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Chemotherapy-Induced Nausea and Vomiting
• Vomiting

Intervention

Drug:
• Experimental: aprepitant
aprepitant powder for suspension, 125 mg/sachet, PO
• Experimental: fosaprepitant
fosaprepitant lyophilized powder for suspension, 115 mg/vial or 150 mg/vial, IV
• Comparator: ondansetron
ondansetron solution for infusion, IV, administered per local standard of care
• Ondansetron
ondansetron solution for infusion, IV, administered per local standard of care
• Dexamethasone
dexamethasone solution for infusion, IV, administered per local standard of care

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Time-Concentration Curve From 0 to 24 Hours (AUC 0-24hr) for Aprepitant	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.	Up to 24 hours post fosaprepitant/aprepitant dose
Primary	Maximum Plasma Concentration (Cmax) for Aprepitant	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.	Up to 72 hours post fosaprepitant/aprepitant dose
Primary	Time to Cmax (Tmax) for Aprepitant	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.	Up to 72 hours post fosaprepitant/aprepitant dose
Primary	Apparent Terminal Half-life (t1/2) for Aprepitant	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.	Up to 72 hours post fosaprepitant/aprepitant dose
Primary	Cmax for Fosaprepitant	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.	Up to 72 hours post fosaprepitant dose
Primary	Tmax for Fosaprepitant	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.	Up to 72 hours post fosaprepitant dose
Primary	Number of Participants Experiencing Adverse Events (AEs)	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.	Up to 14 days after last dose of study drug (Up to 17 days)
Primary	Number of Participants Discontinuing Study Drug Due to an AE	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.	Day 1 up to Day 3
Secondary	Plasma Concentration and PK Parameters of Dexamethasone in Participants From Birth to 1 Year of Age	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.	Up to 24 hours post dexamethasone dose

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