Chemotherapy-Induced Nausea and VomitingPhase 1NCT00818259

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

A Phase 1 study testing Experimental: aprepitant, Experimental: fosaprepitant and Comparator: ondansetron in people with Chemotherapy-Induced Nausea and Vomiting, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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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. Read more about this study

Who is it for?: Ages Up to 17 years
Conditions the study is for: Chemotherapy-Induced Nausea and Vomiting
What is being tested?: Experimental: aprepitant, Experimental: fosaprepitant and Comparator: ondansetron
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 92 participants
Where: No sites listed yet
Study dates: 5 Feb 2009to 20 Jan 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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

About this study

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

Read the 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.

Conditions: Chemotherapy-Induced Nausea and Vomiting
Being tested: Experimental: aprepitant, Experimental: fosaprepitant, Comparator: ondansetron, Ondansetron, Dexamethasone
Medical subject headings: Vomiting

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Experimental: aprepitantDrug
Also called Emend, MK-0869
aprepitant powder for suspension, 125 mg/sachet, PO
Experimental: fosaprepitantDrug
Also called Emend injection, Fosaprepitant Dimeglumine, MK-0517
fosaprepitant lyophilized powder for suspension, 115 mg/vial or 150 mg/vial, IV
Comparator: ondansetronDrug
Also called Zofran
ondansetron solution for infusion, IV, administered per local standard of care
OndansetronDrug
ondansetron solution for infusion, IV, administered per local standard of care
DexamethasoneDrug
dexamethasone solution for infusion, IV, administered per local standard of care

Study groups in NCT00818259
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Experimental: fosaprepitant; Drug: Ondansetron; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: Up to 24 hours post dexamethasone dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Feb 200920 Jan 2014

First posted7 Jan 2009 (estimated)
Study start5 Feb 2009
Primary completion20 Jan 2014
Study completion20 Jan 2014

Why it stopped: Study terminated early prior to completing targeted enrollment of participants \<6 months of age due to recruitment challenges.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Chemotherapy-Induced Nausea and VomitingStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 92 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00818259
Sponsor's protocol ID: 0869-134
Other IDs: 2009_501
Status last verified: Aug 2018
First submitted: 6 Jan 2009
Last updated: 25 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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.
PubMed 25770814

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 4
BMT-08: A Comparative Effectiveness Study of Transdermal Granisetron to Ondansetron
Nausea With Vomiting Chemotherapy-Induced
RecruitingPhase 2
A Study to Evaluate LY3537021 for the Treatment of Nausea and Vomiting Caused by Chemotherapy in Adults With Cancer
Nausea, Vomiting
RecruitingPhase 2
Personalized Antiemetic Regimen According to Patients' Pharmacogenetic Profile
Breast Cancer
RecruitingObservational study
HR20013 for the Prevention of Nausea and Vomiting in Patients With Cancer: A Real-World Study
Chemotherapy-Induced Nausea and Vomiting (CINV), Nausea
RecruitingPhase 1
A Study to Compare the Bioavailability of Ondansetron Following Nasal (NS003) and IV Administration in Healthy Adults
Chemotherapy-Induced Nausea and Vomiting (CINV), Radiotherapy-induced Nausea and Vomiting (RINV)

All Chemotherapy-Induced Nausea and Vomiting trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00818259
Acronym / sponsor ID: 0869-134
Conditions: Chemotherapy-Induced Nausea and Vomiting
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study terminated early prior to completing targeted enrollment of participants \<6 months of age due to recruitment challenges.
Enrolment: 92 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 5 Feb 2009 (actual)
Primary completion: 20 Jan 2014 (actual)
Study completion: 20 Jan 2014 (actual)
First posted: 7 Jan 2009 (estimated)
Results: Posted 18 Nov 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 7

Arm	Type	Receives
Part IA-fosaprepitant 115 mg/aprepitant	Experimental	Drug: Experimental: aprepitant, Drug: Experimental: fosaprepitant, Drug: Ondansetron, Drug: DexamethasoneDay 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.
Part IB-fosaprepitant 150 mg	Experimental	Drug: Experimental: fosaprepitant, Drug: Ondansetron, Drug: DexamethasoneDay 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.
Part IIA-aprepitant 80 mg equiv.	Experimental	Drug: Experimental: aprepitant, Drug: Ondansetron, Drug: DexamethasoneDay 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.
Part IIB-aprepitant 125 mg equiv.	Experimental	Drug: Experimental: aprepitant, Drug: Ondansetron, Drug: DexamethasoneDay 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.
Part III-ondansetron	Active comparator	Drug: Comparator: ondansetron, Drug: DexamethasoneOndansetron 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.
Part IV-aprepitant regimen	Experimental	Drug: Experimental: aprepitant, Drug: Ondansetron, Drug: DexamethasoneDay 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.
Part V-fosaprepitant regimen	Experimental	Drug: Experimental: fosaprepitant, Drug: Ondansetron, Drug: DexamethasoneDay 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.

Who may qualify

Ages: Up to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Experimental: aprepitantAlso: Emend, MK-0869aprepitant powder for suspension, 125 mg/sachet, PO	Drug	Part IA-fosaprepitant 115 mg/aprepitant, Part IIA-aprepitant 80 mg equiv., Part IIB-aprepitant 125 mg equiv., Part IV-aprepitant regimen
Experimental: fosaprepitantAlso: Emend injection, Fosaprepitant Dimeglumine, MK-0517fosaprepitant lyophilized powder for suspension, 115 mg/vial or 150 mg/vial, IV	Drug	Part IA-fosaprepitant 115 mg/aprepitant, Part IB-fosaprepitant 150 mg, Part V-fosaprepitant regimen
Comparator: ondansetronAlso: Zofranondansetron solution for infusion, IV, administered per local standard of care	Drug	Part III-ondansetron
Ondansetronondansetron solution for infusion, IV, administered per local standard of care	Drug	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
Dexamethasonedexamethasone solution for infusion, IV, administered per local standard of care	Drug	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

Primary outcome

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.

1 secondary outcome

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

Results and safety

Results posted to the registry on 18 Nov 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part IA-fosaprepitant 115 mg/Aprepitant	12	12
Part IB-fosaprepitant 150 mg	11	11
Part IIA-aprepitant 80 mg Equiv.	19	19
Part IIB-aprepitant 125 mg Equiv.	20	20
Part III-ondansetron	19	19
Part IV-aprepitant Regimen	0	0
Part IV-Additional Enrollers	5	5
Part V-fosaprepitant Regimen	0	0
Part V-Additional Enrollers	6	6

Primary outcome: 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. Mean (Standard Deviation). Unit: hr*ng/mL

Measure	Part IA-fosaprepitant 115 mg/Aprepitant n = 8	Part IB-fosaprepitant 150 mg n = 11	Part IIA-aprepitant 80 mg Equiv. n = 19	Part IIB-aprepitant 125 mg Equiv. n = 18	Part III-ondansetron n = 0	Part IV-aprepitant Regimen n = 18	Part V-fosaprepitant Regimen n = 21
6 months to <2 years (n=0, 0, 5, 5, 0, 6, 6)	NA (NA)	NA (NA)	20000 (7890)	6310 (2040)	–	21100 (11800)	11700 (6980)
2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7)	NA (NA)	NA (NA)	16400 (8080)	23000 (8390)	–	17300 (5060)	18300 (11100)
6 years to <12 years (n=0, 0, 6, 6, 0, 6, 8)	NA (NA)	NA (NA)	16000 (4810)	22000 (9440)	–	24400 (15800)	19500 (6720)
12 years to 17 years (n=8, 11, 0, 0, 0, 0, 0)	19500 (8010)	30800 (7020)	NA (NA)	NA (NA)	–	NA (NA)	NA (NA)

Population analysed: The population consisted of all participants who received at least one dose of fosaprepitant and/or aprepitant and were evaluable for this PK parameter. No PK assessements were performed on the Part III-ondansetron group; this group received no aprepitant.

Primary outcome: Maximum Plasma Concentration (Cmax) for Aprepitant

Time frame: Up to 72 hours post fosaprepitant/aprepitant dose. Mean (Standard Deviation). Unit: ng/mL

Measure	Part IA-fosaprepitant 115 mg/Aprepitant n = 12	Part IB-fosaprepitant 150 mg n = 11	Part IIA-aprepitant 80 mg Equiv. n = 19	Part IIB-aprepitant 125 mg Equiv. n = 18	Part III-ondansetron n = 0	Part IV-aprepitant Regimen n = 19	Part V-fosaprepitant Regimen n = 22
6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7)	NA (NA)	NA (NA)	1930 (1000)	659 (107)	–	1810 (925)	1700 (636)
2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7)	NA (NA)	NA (NA)	1300 (609)	2100 (1170)	–	1840 (933)	2430 (1100)
6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8)	NA (NA)	NA (NA)	1300 (275)	1930 (873)	–	1800 (1610)	2850 (641)
12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0)	3240 (1280)	5870 (2770)	NA (NA)	NA (NA)	–	NA (NA)	NA (NA)

Primary outcome: Time to Cmax (Tmax) for Aprepitant

Time frame: Up to 72 hours post fosaprepitant/aprepitant dose. Mean (Standard Deviation). Unit: hr

Measure	Part IA-fosaprepitant 115 mg/Aprepitant n = 12	Part IB-fosaprepitant 150 mg n = 11	Part IIA-aprepitant 80 mg Equiv. n = 19	Part IIB-aprepitant 125 mg Equiv. n = 18	Part III-ondansetron n = 0	Part IV-aprepitant Regimen n = 19	Part V-fosaprepitant Regimen n = 22
6 months to <2 years (n=0, 0, 5, 5, 0, 6, 7)	NA (NA)	NA (NA)	2.33 (1.16)	3.45 (2.89)	–	7.34 (8.28)	1.13 (0.17)
2 years to <6 years (n=0, 0, 8, 7, 0, 6, 7)	NA (NA)	NA (NA)	3.78 (1.92)	5.28 (1.97)	–	4.92 (2.20)	1.41 (0.83)
6 years to <12 years (n=0, 0, 6, 6, 0, 7, 8)	NA (NA)	NA (NA)	5.17 (1.83)	3.08 (0.95)	–	6.42 (7.84)	1.07 (0.11)
12 years to 17 years (n=12, 11, 0, 0, 0, 0, 0)	0.41 (0.27)	0.64 (0.30)	NA (NA)	NA (NA)	–	NA (NA)	NA (NA)

Primary outcome: Apparent Terminal Half-life (t1/2) for Aprepitant

Time frame: Up to 72 hours post fosaprepitant/aprepitant dose. Mean (Standard Deviation). Unit: hr

Measure	Part IA-fosaprepitant 115 mg/Aprepitant n = 6	Part IB-fosaprepitant 150 mg n = 11	Part IIA-aprepitant 80 mg Equiv. n = 16	Part IIB-aprepitant 125 mg Equiv. n = 13	Part III-ondansetron n = 0	Part IV-aprepitant Regimen n = 12	Part V-fosaprepitant Regimen n = 21
6 months to <2 years (n=0, 0, 5, 3, 0, 3, 6)	NA (NA)	NA (NA)	7.28 (1.47)	8.09 (2.54)	–	6.18 (4.12)	7.71 (3.10)
2 years to <6 years (n=0, 0, 6, 4, 0, 5, 7)	NA (NA)	NA (NA)	8.27 (2.67)	6.06 (3.03)	–	9.21 (5.57)	6.44 (2.35)
6 years to <12 years (n=0, 0, 5, 6, 0, 4, 8)	NA (NA)	NA (NA)	9.17 (4.00)	6.89 (1.35)	–	10.8 (4.27)	8.76 (3.34)
12 years to 17 years (n=6 11, 0, 0, 0, 0, 0)	11.0 (4.42)	22.2 (19.8)	NA (NA)	NA (NA)	–	NA (NA)	NA (NA)

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to 14 days after last dose of study drug (Up to 17 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part IA-fosaprepitant 115 mg/Aprepitant	4 of 12 (33.3%)	11 of 12 (91.7%)	Not reported
Part IB-fosaprepitant 150 mg	1 of 11 (9.1%)	5 of 11 (45.5%)	Not reported
Part IIA-aprepitant 80 mg Equiv.	7 of 19 (36.8%)	18 of 19 (94.7%)	Not reported
Part IIB-aprepitant 125 mg Equiv.	4 of 19 (21.1%)	15 of 19 (78.9%)	Not reported
Part III-ondansetron	5 of 19 (26.3%)	15 of 19 (78.9%)	Not reported
Part IV-aprepitant Regimen	2 of 20 (10%)	13 of 20 (65%)	Not reported
Part V-fosaprepitant Regimen	9 of 23 (39.1%)	16 of 23 (69.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 25770814Kang 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.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Experimental: aprepitant, Experimental: fosaprepitant and Comparator: ondansetron in people with Chemotherapy-Induced Nausea and Vomiting, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00818259, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2018.