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

NCT00818259 | Terminated Phase 1 Results

• 2 other identifiers: 0869-1342009_501
• Study Type: interventional
• Target: 92
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chemotherapy-Induced Nausea and Vomiting

Outcome Measures

Primary Outcomes (8)

• 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

• 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

• 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

• 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

• 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

• 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

• 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)

• 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 Outcomes (1)

• Plasma Concentration and PK Parameters of Dexamethasone in Participants From Birth to 1 Year of Age

  Up to 24 hours post dexamethasone dose

Study Arms (7)

Part IA-fosaprepitant 115 mg/aprepitant

EXPERIMENTAL

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; Drug: Experimental: fosaprepitant; Drug: Ondansetron; Drug: Dexamethasone

Part IB-fosaprepitant 150 mg

EXPERIMENTAL

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; Drug: Ondansetron; Drug: Dexamethasone

Part IIA-aprepitant 80 mg equiv.

EXPERIMENTAL

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; Drug: Ondansetron; Drug: Dexamethasone

Part IIB-aprepitant 125 mg equiv.

EXPERIMENTAL

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; Drug: Ondansetron; Drug: Dexamethasone

Part III-ondansetron

ACTIVE COMPARATOR

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; Drug: Dexamethasone

Part IV-aprepitant regimen

EXPERIMENTAL

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; Drug: Ondansetron; Drug: Dexamethasone

Part V-fosaprepitant regimen

EXPERIMENTAL

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; Drug: Ondansetron; Drug: Dexamethasone

Interventions

Experimental: aprepitant DRUG

aprepitant powder for suspension, 125 mg/sachet, PO

Also known as: Emend, MK-0869

Part IA-fosaprepitant 115 mg/aprepitant; Part IIA-aprepitant 80 mg equiv.; Part IIB-aprepitant 125 mg equiv.; Part IV-aprepitant regimen

Experimental: fosaprepitant DRUG

fosaprepitant lyophilized powder for suspension, 115 mg/vial or 150 mg/vial, IV

Also known as: Emend injection, Fosaprepitant Dimeglumine, MK-0517

Part IA-fosaprepitant 115 mg/aprepitant; Part IB-fosaprepitant 150 mg; Part V-fosaprepitant regimen

Comparator: ondansetron DRUG

ondansetron solution for infusion, IV, administered per local standard of care

Also known as: Zofran

Part III-ondansetron

Ondansetron DRUG

ondansetron solution for infusion, IV, administered per local standard of care

Part IA-fosaprepitant 115 mg/aprepitant; Part IB-fosaprepitant 150 mg; Part IIA-aprepitant 80 mg equiv.; Part IIB-aprepitant 125 mg equiv.; Part IV-aprepitant regimen; Part V-fosaprepitant regimen

Dexamethasone DRUG

dexamethasone solution for infusion, IV, administered per local standard of care

Part IA-fosaprepitant 115 mg/aprepitant; Part IB-fosaprepitant 150 mg; Part IIA-aprepitant 80 mg equiv.; Part IIB-aprepitant 125 mg equiv.; Part III-ondansetron; Part IV-aprepitant regimen; Part V-fosaprepitant regimen

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related 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)70061-6. Epub 2015 Mar 12.

  PMID: 25770814 RESULT

MeSH Terms

Conditions

Vomiting

Interventions

Aprepitant; fosaprepitant; Ondansetron; Dexamethasone

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2009
• First Posted: January 7, 2009
• Study Start: February 5, 2009
• Primary Completion: January 20, 2014
• Study Completion: January 20, 2014
• Last Updated: September 25, 2018
• Results First Posted: November 18, 2014

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share