Download PDF

Clinical Trial Results:
A Phase IIb, Partially-Blinded Randomized, Active Comparator-Controlled Study to Evaluate the Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Fosaprepitant in Pediatric Patients for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) Associated with Emetogenic Chemotherapy Subtitle: Open-Label Cohort to Further Evaluate the Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Fosaprepitant in Pediatric Patients Birth to <12 Years Old

Summary
EudraCT number	2012-002340-24
Trial protocol	ES PT DE AT HU EE GB LT GR IT RO Outside EU/EEA
Global end of trial date	21 Nov 2016

Results information
Results version number	v1
This version publication date	18 May 2017
First version publication date	18 May 2017
Other versions	v2

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

0517-029

ISRCTN number

US NCT number

NCT01697579

WHO universal trial number (UTN)

Other trial identifiers

Merck Registration Number: MK-0517-029

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

21 Nov 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 Nov 2016

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study was to determine the appropriate dosing regimen of fosaprepitant, when administered with ondansetron (with or without dexamethasone), for the prevention of CINV in children from birth to <17 years of age. Fosaprepitant is a prodrug to aprepitant. All participants who completed the randomized Cycle 1 could elect to receive open-label fosaprepitant during optional Cycles 2-6.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research. The following additional measure defined for this individual study was in place for the protection of trial subjects: Participants will be permitted to take "rescue medication" for established (not anticipated) nausea and vomiting throughout the study.

Background therapy

Evidence for comparator

Actual start date of recruitment

13 Dec 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 3

Country: Number of subjects enrolled

Austria: 16

Country: Number of subjects enrolled

Brazil: 10

Country: Number of subjects enrolled

Canada: 2

Country: Number of subjects enrolled

Chile: 28

Country: Number of subjects enrolled

Estonia: 4

Country: Number of subjects enrolled

Germany: 6

Country: Number of subjects enrolled

Greece: 10

Country: Number of subjects enrolled

Hungary: 13

Country: Number of subjects enrolled

Italy: 12

Country: Number of subjects enrolled

Korea, Republic of: 20

Country: Number of subjects enrolled

Lithuania: 2

Country: Number of subjects enrolled

Peru: 7

Country: Number of subjects enrolled

Portugal: 8

Country: Number of subjects enrolled

Ukraine: 6

Country: Number of subjects enrolled

United Kingdom: 16

Country: Number of subjects enrolled

United States: 6

Country: Number of subjects enrolled

Romania: 22

Country: Number of subjects enrolled

Russian Federation: 7

Country: Number of subjects enrolled

South Africa: 8

Country: Number of subjects enrolled

Spain: 21

Country: Number of subjects enrolled

Turkey: 13

Worldwide total number of subjects

240

EEA total number of subjects

130

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

149

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

This study enrolled participants scheduled to receive chemotherapeutic agent(s) associated with moderate, high, or very high risk of emetogenicity for no more than 5 consecutive days and was expected to receive ondansetron as part of their antiemetic regimen. Additional inclusion and exclusion criteria applied.

Screening details

Participants (2 to <6, 6 to <12 and 12 to17 years-old) were enrolled in a randomized, partially-blinded, study of 4 doses of fosaprepitant and a control in Cycle 1. Participants (0 to <2, 2 to <6 and 6 to <12 years-old) were invited to participate in optional Cycles 2-6 which was an open-label study of 2 doses of fosaprepitant.

Period 1 title

Base Study-Cycle 1

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Fosaprepitant 5 mg/kg-Cycle 1

Arm description

Participants were administered intravenous (IV) Fosaprepitant at the following weight-adjusted doses: Participants 4 months to <12 years old were administered 5 mg/kg (not to exceed 150 mg), Participants 1 to <4 months old were administered 2.5 mg/kg; Participants 0 to <1 month old were administered 1.25 mg/kg. Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), with or without dexamethasone.

Arm type

Experimental

Investigational medicinal product name

Fosaprepitant

Investigational medicinal product code

Other name

Emend® for injection Fosaprepitant dimeglumine MK-0517

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Fosaprepitant 5 mg/kg administered IV as a single dose.

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as specified by local labeling and/or local standard of care

Investigational medicinal product name

Ondansetron

Investigational medicinal product code

Other name

Ondansetron hydrochloride Zofran® Injection

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered IV

Fosaprepitant 3 mg/kg-Cycle 1

Arm description

Arm type

Experimental

Investigational medicinal product name

Fosaprepitant

Investigational medicinal product code

Other name

Emend® for injection Fosaprepitant dimeglumine MK-0517

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Fosaprepitant 3 mg/kg administered IV as a single dose.

Investigational medicinal product name

Ondansetron

Investigational medicinal product code

Other name

Ondansetron hydrochloride Zofran® Injection

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered IV

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as specified by local labeling and/or local standard of care

Fosaprepitant 1.2 mg/kg-Cycle 1

Arm description

Arm type

Experimental

Investigational medicinal product name

Fosaprepitant

Investigational medicinal product code

Other name

Emend® for injection Fosaprepitant dimeglumine MK-0517

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Fosaprepitant 1.2 mg/kg administered IV as a single dose.

Investigational medicinal product name

Ondansetron

Investigational medicinal product code

Other name

Ondansetron hydrochloride Zofran® Injection

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered IV

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as specified by local labeling and/or local standard of care

Fosaprepitant 0.4 mg/kg-Cycle 1

Arm description

Arm type

Experimental

Investigational medicinal product name

Fosaprepitant

Investigational medicinal product code

Other name

Emend® for injection Fosaprepitant dimeglumine MK-0517

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Fosaprepitant 0.4 mg/kg administered IV as a single dose.

Investigational medicinal product name

Ondansetron

Investigational medicinal product code

Other name

Ondansetron hydrochloride Zofran® Injection

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered IV

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as specified by local labeling and/or local standard of care

Placebo Control-Cycle 1

Arm description

Arm type

Placebo

Investigational medicinal product name

Fosaprepitant Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Placebo Fosaprepitant administered IV as a single dose.

Investigational medicinal product name

Ondansetron

Investigational medicinal product code

Other name

Ondansetron hydrochloride Zofran® Injection

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered IV

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as specified by local labeling and/or local standard of care

Number of subjects in period 1	Fosaprepitant 5 mg/kg-Cycle 1	Fosaprepitant 3 mg/kg-Cycle 1	Fosaprepitant 1.2 mg/kg-Cycle 1	Fosaprepitant 0.4 mg/kg-Cycle 1	Placebo Control-Cycle 1
Started	74	43	44	41	38
Completed	72	42	43	40	35
Not completed	2	1	1	1	3
Consent withdrawn by subject	-	1	-	-	-
Adverse event, non-fatal	1	-	-	-	-
Technical problems	-	-	1	1	-
Withdrawal by parent/guardian	1	-	-	-	-
Protocol deviation	-	-	-	-	3

Period 2 title

Optional Extension-Cycles 2-6

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Fosaprepitant 5 mg/kg Cycle 2-6

Arm description

For optional Cycles 2-6, participants from the 5 mg/kg Fosaprepitant arm in Cycle 1 were administered Fosaprepitant 5 mg/kg IV (or age-adjusted equivalent). For Cycle 2, Fosaprepitant was administered IV plus ondansetron with or without dexamethasone. For Cycles 3-6, Fosaprepitant was administered IV plus a 5-hydroxytryptamine 3 (5-HT3) antagonist with or without dexamethasone. Participants 1 year or less were required to receive ondansetron in all cycles as the 5-HT3 antagonist.

Arm type

Experimental

Investigational medicinal product name

Fosaprepitant

Investigational medicinal product code

Other name

Emend® for injection Fosaprepitant dimeglumine MK-0517

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Fosaprepitant 5 mg/kg administered IV as a single dose.

Investigational medicinal product name

5-hydroxytryptamine 3 antagonist

Investigational medicinal product code

Other name

5-HT3

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as specified by local labeling and/or local standard of care

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as specified by local labeling and/or local standard of care

Investigational medicinal product name

Ondansetron

Investigational medicinal product code

Other name

Ondansetron hydrochloride Zofran® Injection

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered IV

Fosaprepitant 3 mg/kg Cycle 2-6

Arm description

For optional Cycles 2-6, participants from Cycle 1 Fosaprepitant arms (3, 1.2, or 0.4 mg/kg) or Cycle 1 Control arm were administered Fosaprepitant 3 mg/kg IV (or age-adjusted equivalent). For Cycle 2, Fosaprepitant was administered IV plus ondansetron with or without dexamethasone. For Cycles 3-6, Fosaprepitant was administered IV plus a 5-HT3 antagonist with or without dexamethasone.

Arm type

Experimental

Investigational medicinal product name

Fosaprepitant

Investigational medicinal product code

Other name

Emend® for injection Fosaprepitant dimeglumine MK-0517

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Fosaprepitant 3 mg/kg administered IV as a single dose.

Investigational medicinal product name

5-hydroxytryptamine 3 antagonist

Investigational medicinal product code

Other name

5-HT3

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as specified by local labeling and/or local standard of care

Investigational medicinal product name

Dexamethasone

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered as specified by local labeling and/or local standard of care

Investigational medicinal product name

Ondansetron

Investigational medicinal product code

Other name

Ondansetron hydrochloride Zofran® Injection

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Administered IV

Number of subjects in period 2 ^[1]	Fosaprepitant 5 mg/kg Cycle 2-6	Fosaprepitant 3 mg/kg Cycle 2-6
Started	47	106
Completed	12	37
Not completed	35	69
Participant moved	-	2
Physician decision	7	11
Technical problems	-	1
Excluded medication	1	2
Additional cycle inclusion/exclusion criteria	4	11
Did not respond to chemotherapy regimen	1	-
Withdrawal by parent/guardian	1	5
Consent withdrawn by subject	-	2
Completed chemotherapy regimen	15	24
Death	-	2
Lost to follow-up	-	1
Non compliance with protocol	6	4
Protocol deviation	-	4

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Participants completing Cycle 1 were invited to participate in optional Cycles 2-6 and received 1 of the 2 dose regimens studied in optional Cycles 2-6.

Baseline characteristics

Top of page

Reporting group title

Fosaprepitant 5 mg/kg-Cycle 1

Reporting group description

Reporting group title

Fosaprepitant 3 mg/kg-Cycle 1

Reporting group description

Reporting group title

Fosaprepitant 1.2 mg/kg-Cycle 1

Reporting group description

Reporting group title

Fosaprepitant 0.4 mg/kg-Cycle 1

Reporting group description

Reporting group title

Placebo Control-Cycle 1

Reporting group description

Reporting group values	Fosaprepitant 5 mg/kg-Cycle 1	Fosaprepitant 3 mg/kg-Cycle 1	Fosaprepitant 1.2 mg/kg-Cycle 1	Fosaprepitant 0.4 mg/kg-Cycle 1	Placebo Control-Cycle 1	Total
Number of subjects	74	43	44	41	38	240
Age Categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	23	0	0	0	0	23
Children (2-11 years)	51	26	27	24	21	149
Adolescents (12-17 years)	0	17	17	17	17	68
Adults (18-64 years)	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0
Age Continuous
Units: months
arithmetic mean (standard deviation)	60.2 ( 42.3 )	123.8 ( 51.3 )	119.4 ( 52.7 )	119.2 ( 54.3 )	122.5 ( 54 )	-
Gender Categorical
Units: Subjects
Female	32	18	23	19	19	111
Male	42	25	21	22	19	129

End points

Top of page

Reporting group title

Fosaprepitant 5 mg/kg-Cycle 1

Reporting group description

Reporting group title

Fosaprepitant 3 mg/kg-Cycle 1

Reporting group description

Reporting group title

Fosaprepitant 1.2 mg/kg-Cycle 1

Reporting group description

Reporting group title

Fosaprepitant 0.4 mg/kg-Cycle 1

Reporting group description

Reporting group title

Placebo Control-Cycle 1

Reporting group description

Reporting group title

Fosaprepitant 5 mg/kg Cycle 2-6

Reporting group description

Reporting group title

Fosaprepitant 3 mg/kg Cycle 2-6

Reporting group description

Subject analysis set title

Fosaprepitant 5 mg/kg-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants were administered IV Fosaprepitant at the following weight-adjusted doses: Participants 4 months to <12 years old were administered 5 mg/kg (not to exceed 150 mg), Participants 1 to <4 months old were administered 2.5 mg/kg; Participants 0 to <1 month old were administered 1.25 mg/kg. Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), with or without dexamethasone. Analysis was in the per-protocol (PP) population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 3 mg/kg-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants 12 to 17 years old were administered 150 mg IV Fosaprepitant. Participants 2 to <12 years old were administered a weight-adjusted dose of 3 mg/kg (not to exceed 150 mg). Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 1.2 mg/kg-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants 12 to 17 years old were administered 60 mg IV Fosaprepitant. Participants 2 to <12 years old were administered a weight-adjusted dose of 1.2 mg/kg (not to exceed 60 mg). Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 0.4 mg/kg-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants 12 to 17 years old were administered 20 mg IV Fosaprepitant. Participants 2 to <12 years old were administered a weight-adjusted dose of 0.4 mg/kg (not to exceed 20 mg). Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Placebo Control-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants were administered IV normal saline at volume to match age and weight specific doses of Fosaprepitant. Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of placebo control and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants were administered IV Fosaprepitant at the following weight-adjusted doses: Participants 4 months to <12 years old were administered 5 mg/kg (not to exceed 150 mg), Participants 1 to <4 months old were administered 2.5 mg/kg; Participants 0 to <1 month old were administered 1.25 mg/kg. Participants were also administered IV ondansetron (0.15 mg/kg x 3 doses for children 6 months to 17 years of age or per local standard of care for children <6 months of age), with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 5 mg/kg: 2 to <6 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants were administered IV Fosaprepitant at the weight-adjusted dose of 5 mg/kg (not to exceed 150 mg). Participants also were administered IV ondansetron at 0.15 mg/kg x 3 doses with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 5 mg/kg: 6 to <12 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants 2 to <12 years old were administered a weight-adjusted dose of 3 mg/kg Fosaprepitant IV (not to exceed 150 mg). Participants were also administered IV ondansetron at 0.15 mg/kg x 3 doses for children 6 months to 17 years of age with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 3 mg/kg: 6 to <12 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Fosaprepitant 3 mg/kg: 12 to 17 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants 12 to 17 years old were administered 150 mg IV Fosaprepitant. Participants were also administered IV ondansetron at 0.15 mg/kg x 3 doses for children 6 months to 17 years of age with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants 2 to <12 years old were administered a weight-adjusted dose of 1.2 mg/kg of Fosaprepitant IV (not to exceed 60 mg). Participants were also administered IV ondansetron at 0.15 mg/kg x 3 doses for children 6 months to 17 years of age with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 1.2 mg/kg: 6 to <12 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Fosaprepitant 1.2 mg/kg: 12 to 17 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants 12 to 17 years old were administered 60 mg IV Fosaprepitant. Participants were also administered IV ondansetron at 0.15 mg/kg x 3 doses for children 6 months to 17 years of age with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants 2 to <12 years old were administered a weight-adjusted dose of 0.4 mg/kg Fosaprepitant IV (not to exceed 20 mg). Participants were also administered IV ondansetron at 0.15 mg/kg x 3 doses for children 6 months to 17 years of age with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 0.4 mg/kg: 6 to <12 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Fosaprepitant 0.4 mg/kg: 12 to 17 Years-Cycle 1

Subject analysis set type

Per protocol

Subject analysis set description

Participants 12 to 17 years old administered 20 mg IV Fosaprepitant. Participants were also administered IV ondansetron at 0.15 mg/kg x 3 doses for children 6 months to 17 years of age with or without dexamethasone. Analysis was in the PP population which includes all participants that received one dose of study therapy and did not have important deviations from the study protocol.

Subject analysis set title

Fosaprepitant 5 mg/kg Cycles 2-6

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Fosaprepitant 3 mg/kg Cycles 2-6

Subject analysis set type

Safety analysis

Subject analysis set description

Primary: Maximum concentration (Cmax) of aprepitant in participants 0 to <2 years of age

Top of page

End point title

Maximum concentration (Cmax) of aprepitant in participants 0 to <2 years of age ^[1]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The Cmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1
Number of subjects analysed	22
Units: ng/mL
arithmetic mean (standard deviation)	3550 ( 1500 )

No statistical analyses for this end point

Primary: Time to maximum concentration (Tmax) of aprepitant in participants 0 to <2 years of age

Top of page

End point title

Time to maximum concentration (Tmax) of aprepitant in participants 0 to <2 years of age ^[2]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1
Number of subjects analysed	22
Units: hours
arithmetic mean (standard deviation)	2.01 ( 2.1 )

No statistical analyses for this end point

Primary: Area under the concentration-time curve of Aprepitant from time 0 to infinity (AUC 0-∞) in participants 0 to <2 years of age

Top of page

End point title

Area under the concentration-time curve of Aprepitant from time 0 to infinity (AUC 0-∞) in participants 0 to <2 years of age ^[3]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1
Number of subjects analysed	16
Units: hr•ng/mL
arithmetic mean (standard deviation)	37200 ( 15800 )

No statistical analyses for this end point

Primary: Area under the concentration-time curve of aprepitant from time 0 to 24 hours (AUC 0-24hr) in participants 0 to <2 years of age

Top of page

End point title

Area under the concentration-time curve of aprepitant from time 0 to 24 hours (AUC 0-24hr) in participants 0 to <2 years of age ^[4]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1
Number of subjects analysed	21
Units: hr•ng/mL
arithmetic mean (standard deviation)	36800 ( 21800 )

No statistical analyses for this end point

Primary: Apparent terminal half-life (t1/2) of aprepitant in participants 0 to <2 years of age

Top of page

End point title

Apparent terminal half-life (t1/2) of aprepitant in participants 0 to <2 years of age ^[5]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1
Number of subjects analysed	16
Units: hours
arithmetic mean (standard deviation)	7.94 ( 2.86 )

No statistical analyses for this end point

Primary: Concentration of aprepitant after 24 hours (C24hr) in participants 0 to <2 years of age

Top of page

End point title

Concentration of aprepitant after 24 hours (C24hr) in participants 0 to <2 years of age ^[6]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1
Number of subjects analysed	21
Units: ng/mL
arithmetic mean (standard deviation)	691 ( 852 )

No statistical analyses for this end point

Primary: Concentration of aprepitant after 48 hours (C48hr) in participants 0 to <2 years of age

Top of page

End point title

Concentration of aprepitant after 48 hours (C48hr) in participants 0 to <2 years of age ^[7]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1
Number of subjects analysed	10
Units: ng/mL
arithmetic mean (standard deviation)	352 ( 929 )

No statistical analyses for this end point

Primary: Apparent total body clearance (CL/F) of aprepitant in participants 0 to <2 years of age

Top of page

End point title

Apparent total body clearance (CL/F) of aprepitant in participants 0 to <2 years of age ^[8]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 0 to <2 Years-Cycle 1
Number of subjects analysed	16
Units: mL/min
arithmetic mean (standard deviation)	24.2 ( 11.9 )

No statistical analyses for this end point

Primary: Cmax of aprepitant in participants 2 to <6 years of age

Top of page

End point title

Cmax of aprepitant in participants 2 to <6 years of age ^[9]

End point description

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1
Number of subjects analysed	25	6	8	6
Units: ng/mL
arithmetic mean (standard deviation)	4270 ( 2370 )	2320 ( 1540 )	2030 ( 1780 )	323 ( 103 )

No statistical analyses for this end point

Primary: Tmax of aprepitant in participants 2 to <6 years of age

Top of page

End point title

Tmax of aprepitant in participants 2 to <6 years of age ^[10]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1
Number of subjects analysed	25	6	8	6
Units: hours
arithmetic mean (standard deviation)	1.9 ( 2.16 )	2.29 ( 2.14 )	1.36 ( 0.868 )	1.34 ( 0.771 )

No statistical analyses for this end point

Primary: AUC 0-∞ of aprepitant in participants 2 to <6 years of age

Top of page

End point title

AUC 0-∞ of aprepitant in participants 2 to <6 years of age ^[11]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1
Number of subjects analysed	20	5	5	4
Units: hr•ng/mL
arithmetic mean (standard deviation)	46400 ( 18600 )	15300 ( 11100 )	16000 ( 9680 )	2070 ( 992 )

No statistical analyses for this end point

Primary: AUC 0-24hr of aprepitant in participants 2 to <6 years of age

Top of page

End point title

AUC 0-24hr of aprepitant in participants 2 to <6 years of age ^[12]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1
Number of subjects analysed	25	6	8	5
Units: hr•ng/mL
arithmetic mean (standard deviation)	45000 ( 23800 )	21800 ( 22200 )	19700 ( 18500 )	1840 ( 742 )

No statistical analyses for this end point

Primary: t1/2 of aprepitant in participants 2 to <6 years of age

Top of page

End point title

t1/2 of aprepitant in participants 2 to <6 years of age ^[13]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1
Number of subjects analysed	20	5	5	4
Units: hours
arithmetic mean (standard deviation)	9.27 ( 4.17 )	6.55 ( 3.62 )	7.27 ( 3.47 )	6.18 ( 3.51 )

No statistical analyses for this end point

Primary: C24hr of aprepitant in participants 2 to <6 years of age

Top of page

End point title

C24hr of aprepitant in participants 2 to <6 years of age ^[14]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1
Number of subjects analysed	25	6	8	6
Units: ng/mL
arithmetic mean (standard deviation)	1060 ( 1020 )	278 ( 398 )	332 ( 430 )	9.23 ( 14.8 )

No statistical analyses for this end point

Primary: C48hr of aprepitant in participants 2 to <6 years of age

Top of page

End point title

C48hr of aprepitant in participants 2 to <6 years of age ^[15]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1
Number of subjects analysed	20	0 ^[16]	0 ^[17]	0 ^[18]
Units: ng/mL
arithmetic mean (standard deviation)	232 ( 471 )	( )	( )	( )

Notes
[16] - Endpoint not calculated
[17] - Endpoint not calculated
[18] - Endpoint not calculated

No statistical analyses for this end point

Primary: CL/F of aprepitant in participants 2 to <6 years of age

Top of page

End point title

CL/F of aprepitant in participants 2 to <6 years of age ^[19]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 3 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 2 to <6 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 2 to <6 Years-Cycle 1
Number of subjects analysed	20	5	5	4
Units: mL/min
arithmetic mean (standard deviation)	31.8 ( 13.8 )	66.2 ( 25.5 )	29.6 ( 22.1 )	48.5 ( 28.4 )

No statistical analyses for this end point

Primary: Cmax of aprepitant in participants 6 to <12 years of age

Top of page

End point title

Cmax of aprepitant in participants 6 to <12 years of age ^[20]

End point description

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 3 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 6 to <12 Years-Cycle 1
Number of subjects analysed	24	14	13	12
Units: ng/mL
arithmetic mean (standard deviation)	4400 ( 1910 )	3550 ( 2460 )	1360 ( 903 )	507 ( 443 )

No statistical analyses for this end point

Primary: Tmax of aprepitant in participants 6 to <12 years of age

Top of page

End point title

Tmax of aprepitant in participants 6 to <12 years of age ^[21]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 3 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 6 to <12 Years-Cycle 1
Number of subjects analysed	24	14	13	12
Units: hours
arithmetic mean (standard deviation)	2.92 ( 5.09 )	1.99 ( 1.62 )	2.14 ( 1.96 )	1.68 ( 2.46 )

No statistical analyses for this end point

Primary: AUC 0-∞ of aprepitant in participants 6 to <12 years of age

Top of page

End point title

AUC 0-∞ of aprepitant in participants 6 to <12 years of age ^[22]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 3 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 6 to <12 Years-Cycle 1
Number of subjects analysed	13	8	9	8
Units: hr•ng/mL
arithmetic mean (standard deviation)	55300 ( 11900 )	34300 ( 20300 )	10700 ( 5440 )	2860 ( 1120 )

No statistical analyses for this end point

Primary: AUC 0-24hr of aprepitant in participants 6 to <12 years of age

Top of page

End point title

AUC 0-24hr of aprepitant in participants 6 to <12 years of age ^[23]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 3 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 6 to <12 Years-Cycle 1
Number of subjects analysed	23	14	13	12
Units: hr•ng/mL
arithmetic mean (standard deviation)	47400 ( 17300 )	29200 ( 14300 )	12000 ( 11000 )	4260 ( 5040 )

No statistical analyses for this end point

Primary: t1/2 of aprepitant in participants 6 to <12 years of age

Top of page

End point title

t1/2 of aprepitant in participants 6 to <12 years of age ^[24]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 3 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 6 to <12 Years-Cycle 1
Number of subjects analysed	13	8	9	8
Units: hours
arithmetic mean (standard deviation)	9.77 ( 2.49 )	7.69 ( 2.09 )	8.23 ( 1.83 )	6.58 ( 2.36 )

No statistical analyses for this end point

Primary: C24hr of aprepitant in participants 6 to <12 years of age

Top of page

End point title

C24hr of aprepitant in participants 6 to <12 years of age ^[25]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 3 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 6 to <12 Years-Cycle 1
Number of subjects analysed	24	14	13	12
Units: ng/mL
arithmetic mean (standard deviation)	1210 ( 1000 )	589 ( 433 )	219 ( 379 )	70.4 ( 136 )

No statistical analyses for this end point

Primary: C48hr of aprepitant in participants 6 to <12 years of age

Top of page

End point title

C48hr of aprepitant in participants 6 to <12 years of age ^[26]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 3 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 6 to <12 Years-Cycle 1
Number of subjects analysed	11	0 ^[27]	0 ^[28]	0 ^[29]
Units: ng/mL
arithmetic mean (standard deviation)	164 ( 124 )	( )	( )	( )

Notes
[27] - Endpoint not calculated
[28] - Endpoint not calculated
[29] - Endpoint not calculated

No statistical analyses for this end point

Primary: CL/F of aprepitant in participants 6 to <12 years of age

Top of page

End point title

CL/F of aprepitant in participants 6 to <12 years of age ^[30]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 3 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 6 to <12 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 6 to <12 Years-Cycle 1
Number of subjects analysed	13	8	9	8
Units: mL/min
arithmetic mean (standard deviation)	42.1 ( 12.7 )	69.2 ( 66.4 )	78.8 ( 39.1 )	89.6 ( 40.9 )

No statistical analyses for this end point

Primary: Cmax of aprepitant in participants 12 to 17 years of age

Top of page

End point title

Cmax of aprepitant in participants 12 to 17 years of age ^[31]

End point description

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 3 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 12 to 17 Years-Cycle 1
Number of subjects analysed	12	12	13
Units: ng/mL
arithmetic mean (standard deviation)	3500 ( 972 )	1180 ( 408 )	582 ( 437 )

No statistical analyses for this end point

Primary: Tmax of aprepitant in participants 12 to 17 years of age

Top of page

End point title

Tmax of aprepitant in participants 12 to 17 years of age ^[32]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The Tmax for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 3 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 12 to 17 Years-Cycle 1
Number of subjects analysed	12	12	13
Units: hours
arithmetic mean (standard deviation)	0.546 ( 0.144 )	0.722 ( 0.608 )	0.736 ( 0.561 )

No statistical analyses for this end point

Primary: AUC 0-∞ of aprepitant in participants 12 to 17 years of age

Top of page

End point title

AUC 0-∞ of aprepitant in participants 12 to 17 years of age ^[33]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-∞ for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 3 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 12 to 17 Years-Cycle 1
Number of subjects analysed	3	8	9
Units: hr•ng/mL
arithmetic mean (standard deviation)	33800 ( 7180 )	12300 ( 4660 )	3500 ( 1430 )

No statistical analyses for this end point

Primary: AUC 0-24hr of aprepitant in participants 12 to 17 years of age

Top of page

End point title

AUC 0-24hr of aprepitant in participants 12 to 17 years of age ^[34]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The AUC 0-24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 3 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 12 to 17 Years-Cycle 1
Number of subjects analysed	12	12	13
Units: hr•ng/mL
arithmetic mean (standard deviation)	30400 ( 8290 )	9700 ( 4200 )	4820 ( 7240 )

No statistical analyses for this end point

Primary: t1/2 of aprepitant in participants 12 to 17 years of age

Top of page

End point title

t1/2 of aprepitant in participants 12 to 17 years of age ^[35]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The t1/2 for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 3 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 12 to 17 Years-Cycle 1
Number of subjects analysed	3	8	9
Units: hours
arithmetic mean (standard deviation)	10.5 ( 1 )	7.92 ( 1.38 )	8.27 ( 1.2 )

No statistical analyses for this end point

Primary: C24hr of aprepitant in participants 12 to 17 years of age

Top of page

End point title

C24hr of aprepitant in participants 12 to 17 years of age ^[36]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The C24hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 3 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 12 to 17 Years-Cycle 1
Number of subjects analysed	12	12	13
Units: ng/mL
arithmetic mean (standard deviation)	735 ( 310 )	142 ( 86.4 )	101 ( 247 )

No statistical analyses for this end point

Primary: C48hr of aprepitant in participants 12 to 17 years of age

Top of page

End point title

C48hr of aprepitant in participants 12 to 17 years of age ^[37]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The C48hr for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 3 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 12 to 17 Years-Cycle 1
Number of subjects analysed	0 ^[38]	0 ^[39]	0 ^[40]
Units: ng/mL
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[38] - Endpoint not calculated
[39] - Endpoint not calculated
[40] - Endpoint not calculated

No statistical analyses for this end point

Primary: CL/F of aprepitant in participants 12 to 17 years of age

Top of page

End point title

CL/F of aprepitant in participants 12 to 17 years of age ^[41]

End point description

Fosaprepitant is a pro-drug that is rapidly converted to aprepitant. Because of this rapid conversion to aprepitant, Fosaprepitant cannot be assessed directly. The pharmacokinetics for each Fosaprepitant dose were determined by analyzing aprepitant in plasma. The CL/F for aprepitant was determined by measuring aprepitant levels at pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion.

End point type

Primary

End point timeframe

Pre-infusion, immediately after infusion, and 2-4, 5-7, 8-10, 23-25, and 46-50 hours post-infusion

Notes
[41] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 3 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 1.2 mg/kg: 12 to 17 Years-Cycle 1	Fosaprepitant 0.4 mg/kg: 12 to 17 Years-Cycle 1
Number of subjects analysed	3	8	9
Units: mL/min
arithmetic mean (standard deviation)	76.2 ( 16.2 )	91.7 ( 32.5 )	105 ( 29 )

No statistical analyses for this end point

Primary: Percentage of participants who experienced at least one adverse event (AE) in Cycle 1

Top of page

End point title

Percentage of participants who experienced at least one adverse event (AE) in Cycle 1 ^[42]

End point description

AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.

End point type

Primary

End point timeframe

Up to 14 days postdose

Notes
[42] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg-Cycle 1	Fosaprepitant 3 mg/kg-Cycle 1	Fosaprepitant 1.2 mg/kg-Cycle 1	Fosaprepitant 0.4 mg/kg-Cycle 1	Placebo Control-Cycle 1
Number of subjects analysed	74	42	43	40	35
Units: Percentage of participants
number (not applicable)	87.8	83.3	90.7	80	77.1

No statistical analyses for this end point

Primary: Percentage of participants who experienced at least one adverse event (AE) in Cycles 2-6

Top of page

End point title

Percentage of participants who experienced at least one adverse event (AE) in Cycles 2-6 ^[43]

End point description

End point type

Primary

End point timeframe

Up to 14 days postdose

Notes
[43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses for group comparisons were planned for this endpoint.

End point values	Fosaprepitant 5 mg/kg Cycles 2-6	Fosaprepitant 3 mg/kg Cycles 2-6
Number of subjects analysed	44	80
Units: Percentage of participants
number (not applicable)	93.6	75.5

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Up to 14 days after the dose of study drug for each cycle

Adverse event reporting additional description

AEs were reported for the All Patients as Treated Population that included all randomized participants who received at least one dose of study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.1

Reporting group title

Fosaprepitant 0.4 mg/kg-Cycle 1

Reporting group description

Reporting group title

Fosaprepitant 1.2 mg/kg-Cycle 1

Reporting group description

Reporting group title

Fosaprepitant 3 mg/kg-Cycle 1

Reporting group description

Reporting group title

Fosaprepitant 5 mg/kg-Cycle 1

Reporting group description

Reporting group title

Placebo Control-Cycle 1

Reporting group description

Reporting group title

Fosaprepitant 3 mg/kg-Cycles 2-6

Reporting group description

Reporting group title

Fosaprepitant 5 mg/kg-Cycles 2-6

Reporting group description

Serious adverse events	Fosaprepitant 0.4 mg/kg-Cycle 1	Fosaprepitant 1.2 mg/kg-Cycle 1	Fosaprepitant 3 mg/kg-Cycle 1	Fosaprepitant 5 mg/kg-Cycle 1	Placebo Control-Cycle 1	Fosaprepitant 3 mg/kg-Cycles 2-6	Fosaprepitant 5 mg/kg-Cycles 2-6
Total subjects affected by serious adverse events
subjects affected / exposed	11 / 40 (27.50%)	14 / 43 (32.56%)	12 / 42 (28.57%)	24 / 74 (32.43%)	12 / 35 (34.29%)	46 / 106 (43.40%)	24 / 47 (51.06%)
number of deaths (all causes)	0	0	0	0	0	1	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0
Investigations
Blood magnesium decreased
subjects affected / exposed	0 / 40 (0.00%)	1 / 43 (2.33%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood phosphorus decreased
subjects affected / exposed	0 / 40 (0.00%)	1 / 43 (2.33%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
C-reactive protein increased
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	1 / 42 (2.38%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	2 / 74 (2.70%)	2 / 35 (5.71%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
White blood cell count decreased
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	1 / 35 (2.86%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug level increased
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
air embolism
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Hydrocephalus
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	1 / 74 (1.35%)	0 / 35 (0.00%)	0 / 106 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	2 / 74 (2.70%)	0 / 35 (0.00%)	1 / 106 (0.94%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile convulsion
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neuropathy peripheral
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neurotoxicity
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	1 / 35 (2.86%)	2 / 106 (1.89%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	7 / 40 (17.50%)	10 / 43 (23.26%)	7 / 42 (16.67%)	13 / 74 (17.57%)	4 / 35 (11.43%)	26 / 106 (24.53%)	18 / 47 (38.30%)
occurrences causally related to treatment / all	0 / 7	0 / 10	0 / 8	0 / 13	0 / 4	0 / 47	0 / 32
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	0 / 40 (0.00%)	1 / 43 (2.33%)	1 / 42 (2.38%)	0 / 74 (0.00%)	1 / 35 (2.86%)	4 / 106 (3.77%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 1	0 / 9	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	1 / 40 (2.50%)	1 / 43 (2.33%)	0 / 42 (0.00%)	0 / 74 (0.00%)	1 / 35 (2.86%)	7 / 106 (6.60%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1	0 / 13	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Pancytopenia
subjects affected / exposed	1 / 40 (2.50%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopaenia
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	2 / 106 (1.89%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 40 (0.00%)	1 / 43 (2.33%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mucosal inflammation
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	2 / 74 (2.70%)	0 / 35 (0.00%)	3 / 106 (2.83%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 40 (2.50%)	0 / 43 (0.00%)	0 / 42 (0.00%)	1 / 74 (1.35%)	1 / 35 (2.86%)	0 / 106 (0.00%)	2 / 47 (4.26%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	1 / 74 (1.35%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 40 (0.00%)	1 / 43 (2.33%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	1 / 40 (2.50%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	0 / 40 (0.00%)	2 / 43 (4.65%)	1 / 42 (2.38%)	0 / 74 (0.00%)	1 / 35 (2.86%)	3 / 106 (2.83%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 0	0 / 1	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	1 / 74 (1.35%)	0 / 35 (0.00%)	4 / 106 (3.77%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Proctalgia
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	1 / 74 (1.35%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Cystitis haemorrhagic
subjects affected / exposed	0 / 40 (0.00%)	1 / 43 (2.33%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	1 / 40 (2.50%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastroenteritis norovirus
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	1 / 74 (1.35%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes virus infection
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	1 / 42 (2.38%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	1 / 35 (2.86%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenic sepsis
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	2 / 42 (4.76%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 40 (2.50%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	1 / 40 (2.50%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin infection
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	1 / 35 (2.86%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tooth infection
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	1 / 74 (1.35%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cytomegalovirus infection
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	4 / 106 (3.77%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile infection
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	2 / 106 (1.89%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes simplex
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	1 / 47 (2.13%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	2 / 47 (4.26%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Device breakage
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	2 / 74 (2.70%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	1 / 40 (2.50%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	0 / 106 (0.00%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	0 / 74 (0.00%)	0 / 35 (0.00%)	1 / 106 (0.94%)	0 / 47 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Fosaprepitant 0.4 mg/kg-Cycle 1	Fosaprepitant 1.2 mg/kg-Cycle 1	Fosaprepitant 3 mg/kg-Cycle 1	Fosaprepitant 5 mg/kg-Cycle 1	Placebo Control-Cycle 1	Fosaprepitant 3 mg/kg-Cycles 2-6	Fosaprepitant 5 mg/kg-Cycles 2-6
Total subjects affected by non serious adverse events
subjects affected / exposed	27 / 40 (67.50%)	33 / 43 (76.74%)	32 / 42 (76.19%)	60 / 74 (81.08%)	24 / 35 (68.57%)	69 / 106 (65.09%)	31 / 47 (65.96%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	4 / 40 (10.00%)	2 / 43 (4.65%)	1 / 42 (2.38%)	6 / 74 (8.11%)	2 / 35 (5.71%)	15 / 106 (14.15%)	2 / 47 (4.26%)
occurrences all number	4	2	2	6	3	22	2
Aspartate aminotransferase increased
subjects affected / exposed	3 / 40 (7.50%)	2 / 43 (4.65%)	2 / 42 (4.76%)	8 / 74 (10.81%)	2 / 35 (5.71%)	13 / 106 (12.26%)	4 / 47 (8.51%)
occurrences all number	3	2	4	8	2	21	5
Neutrophil count decreased
subjects affected / exposed	3 / 40 (7.50%)	5 / 43 (11.63%)	2 / 42 (4.76%)	11 / 74 (14.86%)	2 / 35 (5.71%)	15 / 106 (14.15%)	11 / 47 (23.40%)
occurrences all number	3	5	3	11	2	38	17
Platelet count decreased
subjects affected / exposed	3 / 40 (7.50%)	7 / 43 (16.28%)	5 / 42 (11.90%)	16 / 74 (21.62%)	3 / 35 (8.57%)	15 / 106 (14.15%)	5 / 47 (10.64%)
occurrences all number	3	8	5	16	3	37	8
White blood cell count decreased
subjects affected / exposed	5 / 40 (12.50%)	3 / 43 (6.98%)	2 / 42 (4.76%)	5 / 74 (6.76%)	3 / 35 (8.57%)	13 / 106 (12.26%)	5 / 47 (10.64%)
occurrences all number	5	5	3	5	3	23	6
C-reactive protein increased
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	2 / 42 (4.76%)	2 / 74 (2.70%)	1 / 35 (2.86%)	5 / 106 (4.72%)	3 / 47 (6.38%)
occurrences all number	0	0	2	2	1	8	7
Nervous system disorders
Headache
subjects affected / exposed	3 / 40 (7.50%)	6 / 43 (13.95%)	4 / 42 (9.52%)	2 / 74 (2.70%)	2 / 35 (5.71%)	11 / 106 (10.38%)	2 / 47 (4.26%)
occurrences all number	5	9	7	2	2	15	5
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	9 / 40 (22.50%)	11 / 43 (25.58%)	12 / 42 (28.57%)	27 / 74 (36.49%)	10 / 35 (28.57%)	33 / 106 (31.13%)	14 / 47 (29.79%)
occurrences all number	10	12	12	28	10	54	18
Leukopenia
subjects affected / exposed	4 / 40 (10.00%)	3 / 43 (6.98%)	6 / 42 (14.29%)	5 / 74 (6.76%)	4 / 35 (11.43%)	10 / 106 (9.43%)	6 / 47 (12.77%)
occurrences all number	4	3	6	8	4	22	16
Neutropenia
subjects affected / exposed	7 / 40 (17.50%)	10 / 43 (23.26%)	9 / 42 (21.43%)	18 / 74 (24.32%)	8 / 35 (22.86%)	14 / 106 (13.21%)	4 / 47 (8.51%)
occurrences all number	7	10	10	19	8	19	8
Thrombocytopenia
subjects affected / exposed	9 / 40 (22.50%)	6 / 43 (13.95%)	11 / 42 (26.19%)	11 / 74 (14.86%)	9 / 35 (25.71%)	19 / 106 (17.92%)	10 / 47 (21.28%)
occurrences all number	9	7	11	11	9	44	19
Febrile neutropenia
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	0 / 42 (0.00%)	2 / 74 (2.70%)	0 / 35 (0.00%)	2 / 106 (1.89%)	4 / 47 (8.51%)
occurrences all number	0	0	0	2	0	2	5
General disorders and administration site conditions
Mucosal inflammation
subjects affected / exposed	0 / 40 (0.00%)	5 / 43 (11.63%)	2 / 42 (4.76%)	2 / 74 (2.70%)	0 / 35 (0.00%)	6 / 106 (5.66%)	2 / 47 (4.26%)
occurrences all number	0	5	2	2	0	9	2
Pyrexia
subjects affected / exposed	2 / 40 (5.00%)	3 / 43 (6.98%)	5 / 42 (11.90%)	8 / 74 (10.81%)	3 / 35 (8.57%)	13 / 106 (12.26%)	4 / 47 (8.51%)
occurrences all number	2	4	6	8	4	19	8
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	6 / 40 (15.00%)	4 / 43 (9.30%)	6 / 42 (14.29%)	5 / 74 (6.76%)	4 / 35 (11.43%)	19 / 106 (17.92%)	1 / 47 (2.13%)
occurrences all number	11	6	6	5	4	30	1
Constipation
subjects affected / exposed	3 / 40 (7.50%)	2 / 43 (4.65%)	4 / 42 (9.52%)	9 / 74 (12.16%)	4 / 35 (11.43%)	9 / 106 (8.49%)	2 / 47 (4.26%)
occurrences all number	3	2	4	9	4	9	2
Diarrhoea
subjects affected / exposed	0 / 40 (0.00%)	3 / 43 (6.98%)	2 / 42 (4.76%)	6 / 74 (8.11%)	1 / 35 (2.86%)	10 / 106 (9.43%)	4 / 47 (8.51%)
occurrences all number	0	3	2	6	1	10	5
Nausea
subjects affected / exposed	6 / 40 (15.00%)	3 / 43 (6.98%)	4 / 42 (9.52%)	8 / 74 (10.81%)	2 / 35 (5.71%)	23 / 106 (21.70%)	6 / 47 (12.77%)
occurrences all number	7	3	5	21	2	40	8
Proctalgia
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	1 / 42 (2.38%)	0 / 74 (0.00%)	2 / 35 (5.71%)	2 / 106 (1.89%)	1 / 47 (2.13%)
occurrences all number	0	0	1	0	2	4	1
Stomatitis
subjects affected / exposed	2 / 40 (5.00%)	2 / 43 (4.65%)	2 / 42 (4.76%)	2 / 74 (2.70%)	2 / 35 (5.71%)	8 / 106 (7.55%)	3 / 47 (6.38%)
occurrences all number	2	2	2	2	2	8	4
Vomiting
subjects affected / exposed	9 / 40 (22.50%)	5 / 43 (11.63%)	7 / 42 (16.67%)	14 / 74 (18.92%)	3 / 35 (8.57%)	30 / 106 (28.30%)	12 / 47 (25.53%)
occurrences all number	9	5	8	20	3	69	17
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 40 (2.50%)	2 / 43 (4.65%)	1 / 42 (2.38%)	6 / 74 (8.11%)	1 / 35 (2.86%)	12 / 106 (11.32%)	1 / 47 (2.13%)
occurrences all number	1	2	2	6	1	13	1
Hiccups
subjects affected / exposed	2 / 40 (5.00%)	3 / 43 (6.98%)	2 / 42 (4.76%)	1 / 74 (1.35%)	1 / 35 (2.86%)	3 / 106 (2.83%)	0 / 47 (0.00%)
occurrences all number	10	5	2	1	1	3	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	4 / 42 (9.52%)	5 / 74 (6.76%)	3 / 35 (8.57%)	2 / 106 (1.89%)	2 / 47 (4.26%)
occurrences all number	0	0	4	5	3	2	2
Hypoalbuminaemia
subjects affected / exposed	0 / 40 (0.00%)	0 / 43 (0.00%)	3 / 42 (7.14%)	1 / 74 (1.35%)	0 / 35 (0.00%)	4 / 106 (3.77%)	1 / 47 (2.13%)
occurrences all number	0	0	3	1	0	6	1
Hypokalaemia
subjects affected / exposed	0 / 40 (0.00%)	3 / 43 (6.98%)	4 / 42 (9.52%)	2 / 74 (2.70%)	2 / 35 (5.71%)	15 / 106 (14.15%)	2 / 47 (4.26%)
occurrences all number	0	3	4	2	2	25	2
Hypophosphataemia
subjects affected / exposed	0 / 40 (0.00%)	1 / 43 (2.33%)	3 / 42 (7.14%)	4 / 74 (5.41%)	1 / 35 (2.86%)	9 / 106 (8.49%)	2 / 47 (4.26%)
occurrences all number	0	1	3	4	1	18	3

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

06 Aug 2012

Amendment 01: Revised the study phase from 4 to IIb and added additional ondansetron administration guidance.

19 Dec 2014

Amendment 04: Added an open-label, single-treatment arm, added collection of an optional PK sample approximately 48 hours after completion of fosaprepitant administration, opened enrollment in the birth to <2 years old cohort, and implemented Dexamethasone PK Sampling in participants birth to 1 year old.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
19 May 2014	Enrollment put on hold to allow for authoring of and implementation of Amendment 04.	04 Feb 2015

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Maximum concentration (Cmax) of aprepitant in participants 0 to <2 years of age

Primary: Maximum concentration (Cmax) of aprepitant in participants 0 to <2 years of age

Primary: Time to maximum concentration (Tmax) of aprepitant in participants 0 to <2 years of age

Primary: Time to maximum concentration (Tmax) of aprepitant in participants 0 to <2 years of age

Primary: Area under the concentration-time curve of Aprepitant from time 0 to infinity (AUC 0-∞) in participants 0 to <2 years of age

Primary: Area under the concentration-time curve of Aprepitant from time 0 to infinity (AUC 0-∞) in participants 0 to <2 years of age

Primary: Area under the concentration-time curve of aprepitant from time 0 to 24 hours (AUC 0-24hr) in participants 0 to <2 years of age

Primary: Area under the concentration-time curve of aprepitant from time 0 to 24 hours (AUC 0-24hr) in participants 0 to <2 years of age

Primary: Apparent terminal half-life (t1/2) of aprepitant in participants 0 to <2 years of age

Primary: Apparent terminal half-life (t1/2) of aprepitant in participants 0 to <2 years of age

Primary: Concentration of aprepitant after 24 hours (C24hr) in participants 0 to <2 years of age

Primary: Concentration of aprepitant after 24 hours (C24hr) in participants 0 to <2 years of age

Primary: Concentration of aprepitant after 48 hours (C48hr) in participants 0 to <2 years of age

Primary: Concentration of aprepitant after 48 hours (C48hr) in participants 0 to <2 years of age

Primary: Apparent total body clearance (CL/F) of aprepitant in participants 0 to <2 years of age

Primary: Apparent total body clearance (CL/F) of aprepitant in participants 0 to <2 years of age

Primary: Cmax of aprepitant in participants 2 to <6 years of age

Primary: Cmax of aprepitant in participants 2 to <6 years of age

Primary: Tmax of aprepitant in participants 2 to <6 years of age

Primary: Tmax of aprepitant in participants 2 to <6 years of age

Primary: AUC 0-∞ of aprepitant in participants 2 to <6 years of age

Primary: AUC 0-∞ of aprepitant in participants 2 to <6 years of age

Primary: AUC 0-24hr of aprepitant in participants 2 to <6 years of age

Primary: AUC 0-24hr of aprepitant in participants 2 to <6 years of age

Primary: t1/2 of aprepitant in participants 2 to <6 years of age

Primary: t1/2 of aprepitant in participants 2 to <6 years of age

Primary: C24hr of aprepitant in participants 2 to <6 years of age

Primary: C24hr of aprepitant in participants 2 to <6 years of age

Primary: C48hr of aprepitant in participants 2 to <6 years of age

Primary: C48hr of aprepitant in participants 2 to <6 years of age

Primary: CL/F of aprepitant in participants 2 to <6 years of age

Primary: CL/F of aprepitant in participants 2 to <6 years of age

Primary: Cmax of aprepitant in participants 6 to <12 years of age

Primary: Cmax of aprepitant in participants 6 to <12 years of age

Primary: Tmax of aprepitant in participants 6 to <12 years of age

Primary: Tmax of aprepitant in participants 6 to <12 years of age

Primary: AUC 0-∞ of aprepitant in participants 6 to <12 years of age

Primary: AUC 0-∞ of aprepitant in participants 6 to <12 years of age

Primary: AUC 0-24hr of aprepitant in participants 6 to <12 years of age

Primary: AUC 0-24hr of aprepitant in participants 6 to <12 years of age

Primary: t1/2 of aprepitant in participants 6 to <12 years of age

Primary: t1/2 of aprepitant in participants 6 to <12 years of age

Primary: C24hr of aprepitant in participants 6 to <12 years of age

Primary: C24hr of aprepitant in participants 6 to <12 years of age

Primary: C48hr of aprepitant in participants 6 to <12 years of age

Primary: C48hr of aprepitant in participants 6 to <12 years of age

Primary: CL/F of aprepitant in participants 6 to <12 years of age

Primary: CL/F of aprepitant in participants 6 to <12 years of age

Primary: Cmax of aprepitant in participants 12 to 17 years of age

Primary: Cmax of aprepitant in participants 12 to 17 years of age

Primary: Tmax of aprepitant in participants 12 to 17 years of age

Primary: Tmax of aprepitant in participants 12 to 17 years of age

Primary: AUC 0-∞ of aprepitant in participants 12 to 17 years of age

Primary: AUC 0-∞ of aprepitant in participants 12 to 17 years of age

Primary: AUC 0-24hr of aprepitant in participants 12 to 17 years of age

Primary: AUC 0-24hr of aprepitant in participants 12 to 17 years of age

Primary: t1/2 of aprepitant in participants 12 to 17 years of age

Primary: t1/2 of aprepitant in participants 12 to 17 years of age

Primary: C24hr of aprepitant in participants 12 to 17 years of age

Primary: C24hr of aprepitant in participants 12 to 17 years of age

Primary: C48hr of aprepitant in participants 12 to 17 years of age

Primary: C48hr of aprepitant in participants 12 to 17 years of age

Primary: CL/F of aprepitant in participants 12 to 17 years of age

Primary: CL/F of aprepitant in participants 12 to 17 years of age

Primary: Percentage of participants who experienced at least one adverse event (AE) in Cycle 1

Primary: Percentage of participants who experienced at least one adverse event (AE) in Cycle 1

Primary: Percentage of participants who experienced at least one adverse event (AE) in Cycles 2-6

Primary: Percentage of participants who experienced at least one adverse event (AE) in Cycles 2-6

Adverse events

Adverse events

More information