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    Clinical Trial Results:
    A Multi-center, Open-label, 5-Part Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Aprepitant and Fosaprepitant Dimeglumine in Pediatric Patients Receiving Emetogenic Chemotherapy

    Summary
    EudraCT number
    2006-005515-10
    Trial protocol
    ES   SE   DE   FR   Outside EU/EEA   HU   PL  
    Global end of trial date
    20 Jan 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    01 Mar 2016
    First version publication date
    19 Mar 2015
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    0869-134
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00818259
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    MK-0869-134: Merck protocol number
    Sponsors
    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
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-000406-PIP01-08, EMEA-000144-PIP01-07
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    20 Jan 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Jan 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Jan 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    This study was to determine the appropriate dosing regimen of aprepitant and fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric participants from 0 months to 17 years of age. The purpose of this study was to estimate aprepitant plasma concentration profiles and pharmacokinetic (PK) parameters obtained in participants 0 months to <2 years, 2 to <6 years, 6 to <12 years and 12 to 17 years of age receiving moderately or highly emetogenic chemotherapy. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after intravenous (IV) administration. The birth to one year cohort was to be initiated in Parts III and IV upon completion of Part II (Steps A and B) in participants <6 months of age. The study was terminated early prior to completing targeted enrollment of participants <6 months of age due to recruitment challenges.
    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: Administration of "rescue therapy" was allowed during the treatment phases for nausea and vomiting. Recommended rescue medication were: 5-HT3 antagonists, phenothiazines, butyrophenones, benzamides, corticosteroids, benzodiazepines and domperiodone. Participants/parents/guardians recorded the drug, dosage, date and time that the participant took rescue medication in the patient diary.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    05 Feb 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Brazil: 28
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    Israel: 3
    Country: Number of subjects enrolled
    Peru: 10
    Country: Number of subjects enrolled
    United States: 7
    Country: Number of subjects enrolled
    Norway: 3
    Country: Number of subjects enrolled
    Spain: 21
    Country: Number of subjects enrolled
    Sweden: 6
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    Switzerland: 3
    Worldwide total number of subjects
    92
    EEA total number of subjects
    37
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    19
    Children (2-11 years)
    50
    Adolescents (12-17 years)
    23
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    This study recruited participants who were from birth to 17 years of age and were scheduled to receive moderately to highly nausea-inducing chemotherapy or receive a repeat chemotherapy regimen that was not previously tolerated.

    Pre-assignment
    Screening details
    Of the 92 unique participants who were enrolled and randomized in Parts I (n=23), II (n=39), III (n=19), IV (n=5) and V (n=6), 91 took part in the study. One participant randomized in Part IIB was discontinued prior to treatment.

    Period 1
    Period 1 title
    Randomization Period
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Part IA-fosaprepitant 115 mg/aprepitant
    Arm description
    Day 1, fosaprepitant intravenously (IV) at a dose of 115 mg and Days 2 and 3, aprepitant 80 mg orally (PO), prior to chemotherapy for participants from 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Fosaprepitant dimeglumine
    Investigational medicinal product code
    Other name
    MK-0517
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Day 1, fosaprepitant IV at a dose of 115 mg.

    Investigational medicinal product name
    Aprepitant
    Investigational medicinal product code
    Other name
    MK-0869
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Days 2 and 3, aprepitant 80 mg orally (PO).

    Investigational medicinal product name
    Ondansetron
    Investigational medicinal product code
    Other name
    Zofran®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ondansetron solution for infusion, IV, administered per local standard of care.

    Arm title
    Part IB-fosaprepitant 150 mg
    Arm description
    Day 1, fosaprepitant, IV at a dose of 150 mg, prior to chemotherapy for participants 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Fosaprepitant dimeglumine
    Investigational medicinal product code
    Other name
    MK-0517
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Day 1, fosaprepitant IV at a dose of 150 mg prior to chemotherapy.

    Investigational medicinal product name
    Ondansetron
    Investigational medicinal product code
    Other name
    Zofran®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ondansetron solution for infusion, IV, administered per local standard of care.

    Arm title
    Part IIA-aprepitant 80 mg equiv.
    Arm description
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to <12 years of age - 47 mg/m^2; 4 months to <6 months of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Aprepitant 80 mg equivalent
    Investigational medicinal product code
    Other name
    MK-0869
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Day 1, aprepitant prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to <12 years of age - 47 mg/m^2; 4 months to <6 months of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 monthof age - 0.5 mg/kg.

    Investigational medicinal product name
    Ondansetron
    Investigational medicinal product code
    Other name
    Zofran®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ondansetron solution for infusion, IV, administered per local standard of care.

    Arm title
    Part IIB-aprepitant 125 mg equiv.
    Arm description
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to <12 years of age - 74 mg/m^2; 6 months to <2 years of age - 1.3 mg/kg; 4 months to <6 months of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Aprepitant 125 mg equivalent
    Investigational medicinal product code
    Other name
    MK-0869
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to <12 years of age - 74 mg/m^2; 6 months to <2 years or age - 1.3 mg/kg; 4 months to <6 months of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg.

    Investigational medicinal product name
    Ondansetron
    Investigational medicinal product code
    Other name
    Zofran®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ondansetron solution for infusion, IV, administered per local standard of care.

    Arm title
    Part III-ondansetron
    Arm description
    Ondansetron administered IV per local standard of care on Days 1, 2 and 3 prior to chemotherapy for participants from birth to <12 years of age. The use of IV dexamethsone is optional with the exception of the birth to 1 year cohort. No PK parameters were measured for this group; participants received no fosaprepitant or aprepitant.
    Arm type
    Active comparator

    Investigational medicinal product name
    Ondansetron
    Investigational medicinal product code
    Other name
    Zofran®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ondansetron solution for infusion, IV, administered per local standard of care.

    Arm title
    Part IV-aprepitant regimen
    Arm description
    Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care. The use of dexamethasone IV is optional with the exception of the birth to 1 year old cohort.
    Arm type
    Experimental

    Investigational medicinal product name
    Aprepitant regimen
    Investigational medicinal product code
    Other name
    MK-0869
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg.

    Investigational medicinal product name
    Ondansetron
    Investigational medicinal product code
    Other name
    Zofran®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ondansetron solution for infusion, IV, administered per local standard of care.

    Arm title
    Part V-fosaprepitant regimen
    Arm description
    Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to <12 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Fosaprepitant regimen
    Investigational medicinal product code
    Other name
    MK-0517
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to <12 years of age.

    Investigational medicinal product name
    Ondansetron
    Investigational medicinal product code
    Other name
    Zofran®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ondansetron solution for infusion, IV, administered per local standard of care.

    Number of subjects in period 1
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv. Part III-ondansetron Part IV-aprepitant regimen Part V-fosaprepitant regimen
    Started
    12
    11
    19
    20
    19
    5
    6
    Completed
    12
    11
    19
    20
    19
    5
    6
    Period 2
    Period 2 title
    Part I
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Part IA-fosaprepitant 115 mg/aprepitant
    Arm description
    Day 1, fosaprepitant, IV at a dose of 115 mg and Days 2 and 3, aprepitant 80 mg orally (PO), prior to chemotherapy for participants from 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Fosaprepitant dimeglumine
    Investigational medicinal product code
    Other name
    MK-0517
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Day 1, fosaprepitant IV at a dose of 115 mg.

    Investigational medicinal product name
    Aprepitant
    Investigational medicinal product code
    Other name
    MK-0869
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Days 2 and 3, aprepitant 80 mg orally (PO).

    Arm title
    Part IB-fosaprepitant 150 mg
    Arm description
    Day 1, fosaprepitant, IV at a dose of 150 mg, prior to chemotherapy for participants 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Fosaprepitant dimeglumine
    Investigational medicinal product code
    Other name
    MK-0517
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Day 1, fosaprepitant IV at a dose of 150 mg prior to chemotherapy.

    Number of subjects in period 2
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg
    Started
    12
    11
    Completed
    11
    11
    Not completed
    1
    0
         Consent withdrawn by subject
             1
             -
    Period 3
    Period 3 title
    Part II
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Part IIA-aprepitant 80 mg equiv.
    Arm description
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to <12 years of age - 47 mg/m^2; 4 months to <6 months of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Aprepitant 80 mg equivalent
    Investigational medicinal product code
    Other name
    MK-0869
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Day 1, aprepitant prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to <12 years of age - 47 mg/m^2; 4 months to <6 months of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 monthof age - 0.5 mg/kg.

    Arm title
    Part IIB-aprepitant 125 mg equiv.
    Arm description
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to <12 years of age - 74 mg/m^2; 6 months to <2 years of age - 1.3 mg/kg; 4 months to <6 months of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Aprepitant 125 mg equivalent
    Investigational medicinal product code
    Other name
    MK-0869
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to <12 years of age - 74 mg/m^2; 6 months to <2 years or age - 1.3 mg/kg; 4 months to <6 months of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg.

    Number of subjects in period 3
    Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv.
    Started
    19
    20
    Treated
    19
    19
    Completed
    18
    18
    Not completed
    1
    2
         Physician decision
             1
             -
         Lack of efficacy
             -
             1
         Not treated
             -
             1
    Period 4
    Period 4 title
    Part III
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Part III-ondansetron
    Arm description
    Ondansetron administered IV per local standard of care on Days 1, 2 and 3 prior to chemotherapy for participants from birth to <12 years of age. The use of IV dexamethsone is optional with the exception of the birth to 1 year cohort. No PK parameters were measured for this group; participants received no fosaprepitant or aprepitant.
    Arm type
    Active comparator

    Investigational medicinal product name
    Ondansetron
    Investigational medicinal product code
    Other name
    Zofran®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ondansetron solution for infusion, IV, administered per local standard of care.

    Number of subjects in period 4
    Part III-ondansetron
    Started
    19
    Completed
    19
    Period 5
    Period 5 title
    Part IV
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Part IV-aprepitant regimen
    Arm description
    Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care. The use of dexamethasone IV is optional with the exception of the birth to 1 year old cohort. In addition to newly enrolled participants, participants who complete Part III may participate in Part IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Aprepitant regimen
    Investigational medicinal product code
    Other name
    MK-0869
    Pharmaceutical forms
    Oral powder in sachet
    Routes of administration
    Oral use
    Dosage and administration details
    Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg.

    Number of subjects in period 5 [1]
    Part IV-aprepitant regimen
    Started
    15
    Completed
    19
    Not completed
    1
         Physician decision
             1
    Joined
    5
         Newly enrolled participants
             5
    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 who completed Part III had the option to continue into Part IV, but were not required to continue into Part IV. 15 participants from Part III continued into Part IV.
    Period 6
    Period 6 title
    Part V
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Part V-fosaprepitant regimen
    Arm description
    Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to <12 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV. In addition to newly enrolled participants, participants who complete Part IV may participate in Part V.
    Arm type
    Experimental

    Investigational medicinal product name
    Fosaprepitant regimen
    Investigational medicinal product code
    Other name
    MK-0517
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to <12 years of age.

    Number of subjects in period 6 [2]
    Part V-fosaprepitant regimen
    Started
    17
    Completed
    22
    Not completed
    1
         Adverse event, non-fatal
             1
    Joined
    6
         Newly enrolled participants
             6
    Notes
    [2] - 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 who completed Part IV had the option to continue into Part V, but were not required to continue into Part V. 17 participants from Part IV continued into Part V.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part IA-fosaprepitant 115 mg/aprepitant
    Reporting group description
    Day 1, fosaprepitant intravenously (IV) at a dose of 115 mg and Days 2 and 3, aprepitant 80 mg orally (PO), prior to chemotherapy for participants from 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part IB-fosaprepitant 150 mg
    Reporting group description
    Day 1, fosaprepitant, IV at a dose of 150 mg, prior to chemotherapy for participants 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part IIA-aprepitant 80 mg equiv.
    Reporting group description
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to <12 years of age - 47 mg/m^2; 4 months to <6 months of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part IIB-aprepitant 125 mg equiv.
    Reporting group description
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to <12 years of age - 74 mg/m^2; 6 months to <2 years of age - 1.3 mg/kg; 4 months to <6 months of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part III-ondansetron
    Reporting group description
    Ondansetron administered IV per local standard of care on Days 1, 2 and 3 prior to chemotherapy for participants from birth to <12 years of age. The use of IV dexamethsone is optional with the exception of the birth to 1 year cohort. No PK parameters were measured for this group; participants received no fosaprepitant or aprepitant.

    Reporting group title
    Part IV-aprepitant regimen
    Reporting group description
    Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care. The use of dexamethasone IV is optional with the exception of the birth to 1 year old cohort.

    Reporting group title
    Part V-fosaprepitant regimen
    Reporting group description
    Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to <12 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group values
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv. Part III-ondansetron Part IV-aprepitant regimen Part V-fosaprepitant regimen Total
    Number of subjects
    12 11 19 20 19 5 6 92
    Age categorical
    Units: Subjects
        Infants and toddlers (28 days to <2 years)
    0 0 5 6 6 1 1 19
        Children (2 years to <6 years)
    0 0 8 8 6 0 3 25
        Children (6 years to <12 years)
    0 0 6 6 7 4 2 25
        Adolescents (12 years to 17 years)
    12 11 0 0 0 0 0 23
    Gender categorical
    Units: Subjects
        Female
    7 7 12 14 13 3 6 62
        Male
    5 4 7 6 6 2 0 30

    End points

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    End points reporting groups
    Reporting group title
    Part IA-fosaprepitant 115 mg/aprepitant
    Reporting group description
    Day 1, fosaprepitant intravenously (IV) at a dose of 115 mg and Days 2 and 3, aprepitant 80 mg orally (PO), prior to chemotherapy for participants from 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part IB-fosaprepitant 150 mg
    Reporting group description
    Day 1, fosaprepitant, IV at a dose of 150 mg, prior to chemotherapy for participants 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part IIA-aprepitant 80 mg equiv.
    Reporting group description
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to <12 years of age - 47 mg/m^2; 4 months to <6 months of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part IIB-aprepitant 125 mg equiv.
    Reporting group description
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to <12 years of age - 74 mg/m^2; 6 months to <2 years of age - 1.3 mg/kg; 4 months to <6 months of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part III-ondansetron
    Reporting group description
    Ondansetron administered IV per local standard of care on Days 1, 2 and 3 prior to chemotherapy for participants from birth to <12 years of age. The use of IV dexamethsone is optional with the exception of the birth to 1 year cohort. No PK parameters were measured for this group; participants received no fosaprepitant or aprepitant.

    Reporting group title
    Part IV-aprepitant regimen
    Reporting group description
    Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care. The use of dexamethasone IV is optional with the exception of the birth to 1 year old cohort.

    Reporting group title
    Part V-fosaprepitant regimen
    Reporting group description
    Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to <12 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Reporting group title
    Part IA-fosaprepitant 115 mg/aprepitant
    Reporting group description
    Day 1, fosaprepitant, IV at a dose of 115 mg and Days 2 and 3, aprepitant 80 mg orally (PO), prior to chemotherapy for participants from 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part IB-fosaprepitant 150 mg
    Reporting group description
    Day 1, fosaprepitant, IV at a dose of 150 mg, prior to chemotherapy for participants 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Reporting group title
    Part IIA-aprepitant 80 mg equiv.
    Reporting group description
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to <12 years of age - 47 mg/m^2; 4 months to <6 months of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part IIB-aprepitant 125 mg equiv.
    Reporting group description
    Day 1, aprepitant PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to <12 years of age - 74 mg/m^2; 6 months to <2 years of age - 1.3 mg/kg; 4 months to <6 months of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.
    Reporting group title
    Part III-ondansetron
    Reporting group description
    Ondansetron administered IV per local standard of care on Days 1, 2 and 3 prior to chemotherapy for participants from birth to <12 years of age. The use of IV dexamethsone is optional with the exception of the birth to 1 year cohort. No PK parameters were measured for this group; participants received no fosaprepitant or aprepitant.
    Reporting group title
    Part IV-aprepitant regimen
    Reporting group description
    Day 1, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care. The use of dexamethasone IV is optional with the exception of the birth to 1 year old cohort. In addition to newly enrolled participants, participants who complete Part III may participate in Part IV.
    Reporting group title
    Part V-fosaprepitant regimen
    Reporting group description
    Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to <12 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV. In addition to newly enrolled participants, participants who complete Part IV may participate in Part V.

    Primary: Area Under the Time-Concentration Curve from 0 to 24 hours (AUC0-24hr) for Aprepitant - Parts IA and IB

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    End point title
    Area Under the Time-Concentration Curve from 0 to 24 hours (AUC0-24hr) for Aprepitant - Parts IA and IB [1]
    End point description
    AUC is a measure of the amount of aprepitant in the plasma. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after intravenous (IV) administration. Blood samples for pharmacokinetic (PK) assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hours (hr) post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy.
    End point type
    Primary
    End point timeframe
    Up to 24 hours post fosaprepitant/aprepitant dose
    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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg
    Number of subjects analysed
    8 [2]
    11 [3]
    Units: hr*ng/mL
        arithmetic mean (standard deviation)
    19500 ± 8010
    30800 ± 7020
    Notes
    [2] - Participants who received ≥1 dose fosaprepitant and/or aprepitant and were evaluable for end point.
    [3] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Maximum Plasma Concentration (Cmax) for Aprepitant - Parts IA and IB

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    End point title
    Maximum Plasma Concentration (Cmax) for Aprepitant - Parts IA and IB [4]
    End point description
    Cmax is a measure of the maximum amount of aprepitant in the plasma. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post fosaprepitant/aprepitant dose
    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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg
    Number of subjects analysed
    12 [5]
    11 [6]
    Units: ng/mL
        arithmetic mean (standard deviation)
    3240 ± 1280
    5870 ± 2770
    Notes
    [5] - Participants who received ≥1 dose fosaprepitant and/or aprepitant and were evaluable for end point.
    [6] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Time to Cmax (Tmax) for Aprepitant - Parts IA and IB

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    End point title
    Time to Cmax (Tmax) for Aprepitant - Parts IA and IB [7]
    End point description
    Tmax is a measure of the amount of time after dosing to when the maximum concentration of aprepitant was achieved. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post fosaprepitant/aprepitant dose
    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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg
    Number of subjects analysed
    12 [8]
    11 [9]
    Units: hr
        arithmetic mean (standard deviation)
    0.41 ± 0.27
    0.64 ± 0.3
    Notes
    [8] - Participants who received ≥1 dose fosaprepitant and/or aprepitant and were evaluable for end point.
    [9] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Apparent Terminal Half-life (t1/2) for Aprepitant - Parts IA and IB

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    End point title
    Apparent Terminal Half-life (t1/2) for Aprepitant - Parts IA and IB [10]
    End point description
    t1/2 is the amount of time from dosing until half of the aprepitant was metabolized from the body. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB - Predose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post fosaprepitant/aprepitant dose
    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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg
    Number of subjects analysed
    6 [11]
    11 [12]
    Units: hr
        arithmetic mean (standard deviation)
    11 ± 4.42
    22.2 ± 19.8
    Notes
    [11] - Participants who received ≥1 dose fosaprepitant and/or aprepitant and were evaluable for end point.
    [12] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Cmax for Fosaprepitant - Parts IA and IB

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    End point title
    Cmax for Fosaprepitant - Parts IA and IB [13]
    End point description
    Cmax is a measure of the maximum amount of fosaprepitant in the plasma. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose, Part IB - Pre-dose and 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post fosaprepitant dose. No PK analyses were performed on the Part IA group because blood samples were not handled correctly.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post fosaprepitant dose
    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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg
    Number of subjects analysed
    0 [14]
    11 [15]
    Units: ng/mL
        arithmetic mean (standard deviation)
    ±
    1310 ± 964
    Notes
    [14] - No PK analyses were performed on the Part IA group because blood samples were not handled correctly.
    [15] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Tmax for Fosaprepitant - Parts IA and IB

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    End point title
    Tmax for Fosaprepitant - Parts IA and IB [16]
    End point description
    Tmax is a measure of the amount of time after dosing to when the maximum concentration of fosaprepitant was achieved. Blood samples for PK assessment were collected at the following time points: Part IA - Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 24 hr post fosaprepitant dose; Part IB – Pre-dose and 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post fosaprepitant dose. No PK analyses were performed on the Part IA group because blood samples were not handled correctly.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post fosaprepitant dose
    Notes
    [16] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg
    Number of subjects analysed
    0 [17]
    11 [18]
    Units: hr
        arithmetic mean (standard deviation)
    ±
    0.614 ± 0.251
    Notes
    [17] - No PK analyses were performed on the Part IA group because blood samples were not handled correctly.
    [18] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Number of Participants Experiencing at Least One Adverse Event (AE)

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    End point title
    Number of Participants Experiencing at Least One Adverse Event (AE) [19]
    End point description
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Participants were monitored for the occurrence AEs for up to 14 days after last dose of study drug.
    End point type
    Primary
    End point timeframe
    Up to 14 days after last dose of study drug (Up to 17 days)
    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 were planned for this safety end point.
    End point values
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv. Part III-ondansetron Part IV-aprepitant regimen Part V-fosaprepitant regimen
    Number of subjects analysed
    12 [20]
    11 [21]
    19 [22]
    19 [23]
    19 [24]
    20 [25]
    23 [26]
    Units: Participants
    11
    6
    18
    16
    15
    13
    17
    Notes
    [20] - Participants who received ≥1 dose of study drug.
    [21] - Participants who received ≥1 dose of study drug.
    [22] - Participants who received ≥1 dose of study drug.
    [23] - Participants who received ≥1 dose of study drug.
    [24] - Participants who received ≥1 dose of study drug.
    [25] - Participants who received ≥1 dose of study drug.
    [26] - Participants who received ≥1 dose of study drug.
    No statistical analyses for this end point

    Primary: Number of Participants Discontinuing Study Drug Due to an AE

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    End point title
    Number of Participants Discontinuing Study Drug Due to an AE [27]
    End point description
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. The numbers of participants who discontinued study drug due to an AE are summarized.
    End point type
    Primary
    End point timeframe
    Day 1 up to Day 3
    Notes
    [27] - 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 were planned for this safety end point.
    End point values
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv. Part III-ondansetron Part IV-aprepitant regimen Part V-fosaprepitant regimen
    Number of subjects analysed
    12 [28]
    11 [29]
    19 [30]
    19 [31]
    19 [32]
    20 [33]
    23 [34]
    Units: Participants
    0
    0
    0
    0
    0
    0
    1
    Notes
    [28] - Participants who received ≥1 dose of study drug.
    [29] - Participants who received ≥1 dose of study drug.
    [30] - Participants who received ≥1 dose of study drug.
    [31] - Participants who received ≥1 dose of study drug.
    [32] - Participants who received ≥1 dose of study drug.
    [33] - Participants who received ≥1 dose of study drug.
    [34] - Participants who received ≥1 dose of study drug.
    No statistical analyses for this end point

    Primary: AUC0-24hr for Aprepitant - Parts IIA and IIB

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    End point title
    AUC0-24hr for Aprepitant - Parts IIA and IIB [35]
    End point description
    AUC is a measure of the amount of aprepitant in the plasma. Blood samples for PK assessment were collected at the following time points: Parts IIA and IIB - Pre-dose and 1.5, 3, 4, 6, 8 and 24 hr post aprepitant dose.
    End point type
    Primary
    End point timeframe
    Up to 24 hours post aprepitant dose
    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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv.
    Number of subjects analysed
    19 [36]
    18 [37]
    Units: hr*ng/mL
    arithmetic mean (standard deviation)
        6 months to <2 years (n=5, 5)
    20000 ± 7890
    6310 ± 2040
        2 years to <6 years (n=8, 7)
    16400 ± 8080
    23000 ± 8390
        6 years to <12 years (n=6, 6)
    16000 ± 4810
    22000 ± 9440
    Notes
    [36] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    [37] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: AUC0-24hr for Aprepitant – Part IV

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    End point title
    AUC0-24hr for Aprepitant – Part IV [38]
    End point description
    AUC is a measure of the amount of aprepitant in the plasma. Blood samples for PK assessment were collected at the following time points: Part IV - Pre-dose and 1.5, 3, 4, 6, 8 and 24 hr post aprepitant dose.
    End point type
    Primary
    End point timeframe
    Up to 24 hours post aprepitant dose
    Notes
    [38] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IV-aprepitant regimen
    Number of subjects analysed
    18 [39]
    Units: hr*ng/mL
    arithmetic mean (standard deviation)
        6 months to <2 years (n=6)
    21100 ± 11800
        2 years to <6 years (n=6)
    17300 ± 5060
        6 years to <12 years (n=6)
    24400 ± 15800
    Notes
    [39] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: AUC0-24hr for Aprepitant – Part V

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    End point title
    AUC0-24hr for Aprepitant – Part V [40]
    End point description
    AUC is a measure of the amount of aprepitant in the plasma. Blood samples for PK assessment were collected at the following time points: Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy.
    End point type
    Primary
    End point timeframe
    Up to 24 hours post aprepitant dose
    Notes
    [40] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part V-fosaprepitant regimen
    Number of subjects analysed
    21 [41]
    Units: hr*ng/mL
    arithmetic mean (standard deviation)
        6 months to <2 years (n=6)
    11700 ± 6980
        2 years to <6 years (n=7)
    18300 ± 11100
        6 years to <12 years (n=8)
    19500 ± 6720
    Notes
    [41] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Cmax for Aprepitant - Parts IIA and IIB

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    End point title
    Cmax for Aprepitant - Parts IIA and IIB [42]
    End point description
    Cmax is a measure of the maximum amount of aprepitant in the plasma. Blood samples for PK assessment were collected at the following time points: Parts IIA and IIB - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post aprepitant dose
    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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv.
    Number of subjects analysed
    19 [43]
    18 [44]
    Units: ng/mL
    arithmetic mean (standard deviation)
        6 months to <2 years (n=5, 5)
    1930 ± 1000
    659 ± 107
        2 years to <6 years (n=8, 7)
    1300 ± 609
    2100 ± 1170
        6 years to <12 years (n=6, 6)
    1300 ± 275
    1930 ± 873
    Notes
    [43] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    [44] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Cmax for Aprepitant - Part IV

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    End point title
    Cmax for Aprepitant - Part IV [45]
    End point description
    Cmax is a measure of the maximum amount of aprepitant in the plasma. Blood samples for PK assessment were collected at the following time points: Part IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post aprepitant dose
    Notes
    [45] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IV-aprepitant regimen
    Number of subjects analysed
    19 [46]
    Units: ng/mL
    arithmetic mean (standard deviation)
        6 months to <2 years (n=6)
    1810 ± 925
        2 years to <6 years (n=6)
    1840 ± 933
        6 years to <12 years (n=7)
    1800 ± 1610
    Notes
    [46] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Cmax for Aprepitant - Part V

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    End point title
    Cmax for Aprepitant - Part V [47]
    End point description
    Cmax is a measure of the maximum amount of aprepitant in the plasma. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post fosaprepitant dose
    Notes
    [47] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part V-fosaprepitant regimen
    Number of subjects analysed
    22 [48]
    Units: ng/mL
    arithmetic mean (standard deviation)
        6 months to <2 years (n=7)
    1700 ± 636
        2 years to <6 years (n=7)
    2430 ± 1100
        6 years to <12 years (n=8)
    2850 ± 641
    Notes
    [48] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Tmax for Aprepitant - Parts IIA and IIB

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    End point title
    Tmax for Aprepitant - Parts IIA and IIB [49]
    End point description
    Tmax is a measure of the amount of time after dosing to when the maximum concentration of aprepitant was achieved. Blood samples for PK assessment were collected at the following time points: Parts IIA and IIB - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post aprepitant dose
    Notes
    [49] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv.
    Number of subjects analysed
    19 [50]
    18 [51]
    Units: hr
    arithmetic mean (standard deviation)
        6 months to <2 years (n=5, 5)
    2.33 ± 1.16
    3.45 ± 2.89
        2 years to <6 years (n=8, 7)
    3.78 ± 1.92
    5.28 ± 1.97
        6 years to <12 years (n=6, 6)
    5.17 ± 1.83
    3.08 ± 0.95
    Notes
    [50] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    [51] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Tmax for Aprepitant - Part V

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    End point title
    Tmax for Aprepitant - Part V [52]
    End point description
    Tmax is a measure of the amount of time after dosing to when the maximum concentration of aprepitant was achieved. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part V - Pre-dose and -0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post fosaprepitant dose
    Notes
    [52] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part V-fosaprepitant regimen
    Number of subjects analysed
    22 [53]
    Units: hr
    arithmetic mean (standard deviation)
        6 months to <2 years (n=7)
    1.13 ± 0.17
        2 years to <6 years (n=7)
    1.41 ± 0.83
        6 years to <12 years (n=8)
    1.07 ± 0.11
    Notes
    [53] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Tmax for Aprepitant - Part IV

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    End point title
    Tmax for Aprepitant - Part IV [54]
    End point description
    Tmax is a measure of the amount of time after dosing to when the maximum concentration of aprepitant was achieved. Blood samples for PK assessment were collected at the following time points: Part IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post aprepitant dose
    Notes
    [54] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IV-aprepitant regimen
    Number of subjects analysed
    19 [55]
    Units: hr
    arithmetic mean (standard deviation)
        6 months to <2 years (n=6)
    7.34 ± 8.28
        2 years to <6 years (n=6)
    4.92 ± 2.2
        6 years to <12 years (n=7)
    6.42 ± 7.84
    Notes
    [55] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: t1/2 for Aprepitant - Parts IIA and IIB

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    End point title
    t1/2 for Aprepitant - Parts IIA and IIB [56]
    End point description
    t1/2 is the amount of time from dosing until half of the aprepitant was metabolized from the body. Blood samples for PK assessment were collected at the following time points: Parts IIA and IIB - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post aprepitant dose
    Notes
    [56] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv.
    Number of subjects analysed
    16 [57]
    13 [58]
    Units: hr
    arithmetic mean (standard deviation)
        6 months to <2 years (n=5, 3)
    7.28 ± 1.47
    8.09 ± 2.54
        2 years to <6 years (n=6, 4)
    8.27 ± 2.67
    6.06 ± 3.03
        6 years to <12 years (n=5, 6)
    9.17 ± 4
    6.89 ± 1.35
    Notes
    [57] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    [58] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: t1/2 for Aprepitant - Part IV

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    End point title
    t1/2 for Aprepitant - Part IV [59]
    End point description
    t1/2 is the amount of time from dosing until half of the aprepitant was metabolized from the body. Blood samples for PK assessment were collected at the following time points: Part IV - Pre-dose and 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post aprepitant dose.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post aprepitant dose
    Notes
    [59] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part IV-aprepitant regimen
    Number of subjects analysed
    12 [60]
    Units: hr
    arithmetic mean (standard deviation)
        6 months to <2 years (n=3)
    6.18 ± 4.12
        2 years to <6 years (n=5)
    9.21 ± 5.57
        6 years to <12 years (n=4)
    10.8 ± 4.27
    Notes
    [60] - Participants who received ≥1 dose aprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: t1/2 for Aprepitant - Part V

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    End point title
    t1/2 for Aprepitant - Part V [61]
    End point description
    t1/2 is the amount of time from dosing until half of the aprepitant was metabolized from the body. Fosaprepitant is a prodrug for aprepitant and is rapidly converted to aprepitant after IV administration. Blood samples for PK assessment were collected at the following time points: Part V - Pre-dose and - 0.75, -0.5, 0, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post fosaprepitant dose
    Notes
    [61] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part V-fosaprepitant regimen
    Number of subjects analysed
    21 [62]
    Units: hr
    arithmetic mean (standard deviation)
        6 months to <2 years (n=6)
    7.71 ± 3.1
        2 years to <6 years (n=7)
    6.44 ± 2.35
        6 years to <12 years (n=8)
    8.76 ± 3.34
    Notes
    [62] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Cmax for Fosaprepitant - Part V

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    End point title
    Cmax for Fosaprepitant - Part V [63]
    End point description
    Cmax is a measure of the maximum amount of fosaprepitant in the plasma. Blood samples for PK assessment were collected at the following time points: Part V - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post fosaprepitant dose
    Notes
    [63] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part V-fosaprepitant regimen
    Number of subjects analysed
    23 [64]
    Units: ng/mL
    arithmetic mean (standard deviation)
        6 months to <2 years (n=7)
    2756 ± 3364
        2 years to <6 years (n=8)
    3034 ± 1718
        6 years to <12 years (n=8)
    1654 ± 1995
    Notes
    [64] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Primary: Tmax for Fosaprepitant - Part V

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    End point title
    Tmax for Fosaprepitant - Part V [65]
    End point description
    Tmax is a measure of the amount of time after dosing to when the maximum concentration of fosaprepitant was achieved. Blood samples for PK assessment were collected at the following time points: Part V - Pre-dose and -0.75, -0.5, 0, 0.5, 1.5, 3, 4, 6, 8, 24, 48 and 72 hr post start of chemotherapy.
    End point type
    Primary
    End point timeframe
    Up to 72 hours post fosaprepitant dose
    Notes
    [65] - 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: The design and sample size of this study were not designed to test hypotheses; therefore no statistical analyses were planned for this PK end point.
    End point values
    Part V-fosaprepitant regimen
    Number of subjects analysed
    22 [66]
    Units: hr
    arithmetic mean (standard deviation)
        6 months to <2 years (n=7)
    1.13 ± 0.175
        2 years to <6 years (n=7)
    1.05 ± 0.089
        6 years to <12 years (n=8)
    1.04 ± 0.088
    Notes
    [66] - Participants who received ≥1 dose fosaprepitant and were evaluable for end point.
    No statistical analyses for this end point

    Secondary: Plasma Concentration and PK Parameters of Dexamethasone in Participants from Birth to 1 Year of Age

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    End point title
    Plasma Concentration and PK Parameters of Dexamethasone in Participants from Birth to 1 Year of Age
    End point description
    Blood samples for PK assessment were to be collected at the following time points: Parts II and V - Pre-dose and 1.5, 3, 4, 6, 8 and 24 hr post start of chemotherapy; Parts III and IV - Immediately after infusion of dexamethsone and 0.5, 1.5, 3, 8 and 24 hr post start of chemotherapy. No analyses were conducted; enrollment in the birth to 1 year cohort was not opened as enrollment in birth to <6 month olds in Part II was unsuccessful.
    End point type
    Secondary
    End point timeframe
    Up to 24 hours post dexamethasone dose
    End point values
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv. Part III-ondansetron Part IV-aprepitant regimen Part V-fosaprepitant regimen
    Number of subjects analysed
    0 [67]
    0 [68]
    0 [69]
    0 [70]
    0 [71]
    0 [72]
    0 [73]
    Units: ng/mL
        arithmetic mean (standard deviation)
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    Notes
    [67] - Analysis not conducted; enrollment in birth to 1 year cohort not opened.
    [68] - Analysis not conducted; enrollment in birth to 1 year cohort not opened.
    [69] - Analysis not conducted; enrollment in birth to 1 year cohort not opened.
    [70] - Analysis not conducted; enrollment in birth to 1 year cohort not opened.
    [71] - Analysis not conducted; enrollment in birth to 1 year cohort not opened.
    [72] - Analysis not conducted; enrollment in birth to 1 year cohort not opened.
    [73] - Analysis not conducted; enrollment in birth to 1 year cohort not opened.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 14 days after last dose of study drug (Up to 17 days)
    Adverse event reporting additional description
    The population consisted of all randomized participants who received ≥1 dose of study drug. Participants who completed Part III could enter Part IV and participants who completed Part IV could enter Part V. Participants are counted once for each study part in which they participated. AEs are reported based on the study drug taken at the time of AE.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Part IA-fosaprepitant 115 mg/aprepitant
    Reporting group description
    Day 1, fosaprepitant, IV at a dose of 115 mg and Days 2 and 3, aprepitant 80 mg PO, prior to chemotherapy for participants from 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part IB-fosaprepitant 150 mg
    Reporting group description
    Day 1, fosaprepitant, IV at a dose of 150 mg, prior to chemotherapy for participants 12 to 17 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part IIA-aprepitant 80 mg equiv.
    Reporting group description
    Day 1, aprepitant, PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 6 months to <12 years of age - 47 mg/m^2; 4 months to <6 months of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part IIB-aprepitant 125 mg equiv.
    Reporting group description
    Day 1, aprepitant, PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 2 years to <12 years of age - 74 mg/m^2; 6 months to <2 years of age - 1.3 mg/kg; 4 months to <6 months of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Reporting group title
    Part III-ondansetron
    Reporting group description
    Ondansetron administered IV per local standard of care on Days 1, 2 and 3 prior to chemotherapy for participants from birth to <12 years of age. The use of IV dexamethsone is optional with the exception of the birth to 1 year cohort. No PK parameters were measured for this group; participants received no fosaprepitant or aprepitant.

    Reporting group title
    Part IV-aprepitant regimen
    Reporting group description
    Day 1, aprepitant, PO prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 3.0 mg/kg; 1 month to <4 months of age - 1.5 mg/kg; birth to <1 month of age - 0.75 mg/kg; Days 2 and 3, aprepitant, PO, prior to chemotherapy at the dosing regimens listed for the following age ranges: 4 months to <12 years of age - 2.0 mg/kg; 1 month to <4 months of age - 1.0 mg/kg; birth to <1 month of age - 0.5 mg/kg. Participants also receive ondansetron IV as per local standard of care. The use of dexamethasone IV is optional with the exception of the birth to 1 year old cohort.

    Reporting group title
    Part V-fosaprepitant regimen
    Reporting group description
    Day 1, fosaprepitant, IV at a dose of 3 mg/kg prior to chemotherapy for participants 6 months to <12 years of age. Participants also receive ondansetron IV as per local standard of care, with or without dexamethasone IV.

    Serious adverse events
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv. Part III-ondansetron Part IV-aprepitant regimen Part V-fosaprepitant regimen
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 12 (33.33%)
    1 / 11 (9.09%)
    7 / 19 (36.84%)
    4 / 19 (21.05%)
    5 / 19 (26.32%)
    2 / 20 (10.00%)
    9 / 23 (39.13%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Wound dehiscence
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         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
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (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
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 11 (0.00%)
    4 / 19 (21.05%)
    2 / 19 (10.53%)
    4 / 19 (21.05%)
    2 / 20 (10.00%)
    4 / 23 (17.39%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
    0 / 2
    0 / 4
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphopenia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (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
    Neutropenia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    2 / 23 (8.70%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    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
    Thrombocytopenia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    General disorders and administration site conditions
    Device dislocation
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (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
    Mucosal inflammation
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         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
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (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
    Enteritis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (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
    Nausea
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (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
    Vomiting
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         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
    Hypokalaemia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (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
    Hyponatraemia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Catheter site cellulitis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (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
    Enterobacter bacteraemia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (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
    Septic shock
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (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
    Vulval abscess
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Part IA-fosaprepitant 115 mg/aprepitant Part IB-fosaprepitant 150 mg Part IIA-aprepitant 80 mg equiv. Part IIB-aprepitant 125 mg equiv. Part III-ondansetron Part IV-aprepitant regimen Part V-fosaprepitant regimen
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 12 (91.67%)
    5 / 11 (45.45%)
    18 / 19 (94.74%)
    15 / 19 (78.95%)
    15 / 19 (78.95%)
    13 / 20 (65.00%)
    16 / 23 (69.57%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Oncologic complication
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    1
    Fatigue
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    1
    Chills
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Hyperthermia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Implant site reaction
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Irritability
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    Pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Product taste abnormal
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    1 / 20 (5.00%)
    7 / 23 (30.43%)
         occurrences all number
    0
    0
    2
    1
    1
    1
    8
    Secretion discharge
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Reproductive system and breast disorders
    Perineal erythema
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Excoriation
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Traumatic haematoma
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    1 / 23 (4.35%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    1
    Blood bicarbonate decreased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Blood glucose increased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Blood potassium decreased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Blood phosphorus decreased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Blood sodium decreased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    0
    0
    Blood uric acid increased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Body temperature increased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Drug clearance decreased
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Glucose urine present
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    1
    1
    1
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    3 / 19 (15.79%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    3 / 19 (15.79%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    1
    3
    0
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    3 / 19 (15.79%)
    1 / 20 (5.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    1
    3
    1
    0
    Red blood cell count decreased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Staphylococcus test positive
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
    3 / 19 (15.79%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    2
    3
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Congenital, familial and genetic disorders
    Aplasia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Asthmatic crisis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Cough
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    1 / 20 (5.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    2
    Dyspnoea
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 12 (25.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    5 / 19 (26.32%)
    5 / 19 (26.32%)
    3 / 20 (15.00%)
    3 / 23 (13.04%)
         occurrences all number
    3
    0
    0
    5
    5
    3
    3
    Coagulopathy
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Bone marrow failure
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Febrile neutropenia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
    1 / 20 (5.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    1
    0
    Leukocytosis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Leukopenia
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Lymphopenia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    4 / 19 (21.05%)
    3 / 19 (15.79%)
    3 / 20 (15.00%)
    5 / 23 (21.74%)
         occurrences all number
    1
    0
    2
    4
    3
    3
    5
    Thrombocytopenia
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    3 / 19 (15.79%)
    4 / 19 (21.05%)
    5 / 20 (25.00%)
    4 / 23 (17.39%)
         occurrences all number
    2
    0
    0
    3
    5
    5
    5
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Dizziness
         subjects affected / exposed
    3 / 12 (25.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    1 / 23 (4.35%)
         occurrences all number
    3
    0
    0
    0
    0
    1
    1
    Formication
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Parosmia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Headache
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    1 / 19 (5.26%)
    3 / 19 (15.79%)
    1 / 20 (5.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    0
    4
    1
    3
    1
    2
    Sensory disturbance
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    Eye irritation
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Eye pruritus
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Eye pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Vision blurred
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    4 / 19 (21.05%)
    1 / 19 (5.26%)
    1 / 20 (5.00%)
    3 / 23 (13.04%)
         occurrences all number
    2
    0
    2
    4
    1
    1
    4
    Constipation
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    3 / 19 (15.79%)
    1 / 20 (5.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    1
    0
    0
    3
    1
    1
    Diarrhoea
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    3 / 19 (15.79%)
    1 / 20 (5.00%)
    2 / 23 (8.70%)
         occurrences all number
    0
    1
    1
    1
    3
    1
    2
    Flatulence
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Gingival bleeding
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Haematemesis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Lip blister
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Nausea
         subjects affected / exposed
    3 / 12 (25.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    6 / 19 (31.58%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    1 / 23 (4.35%)
         occurrences all number
    4
    0
    3
    6
    0
    2
    1
    Odynophagia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    1
    0
    2
    0
    0
    0
    1
    Perianal erythema
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Retching
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    2
    1
    1
    0
    0
    Stomatitis
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    3 / 19 (15.79%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    3
    0
    0
    Salivary hypersecretion
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Tongue ulceration
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Toothache
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    5 / 12 (41.67%)
    0 / 11 (0.00%)
    9 / 19 (47.37%)
    8 / 19 (42.11%)
    2 / 19 (10.53%)
    1 / 20 (5.00%)
    5 / 23 (21.74%)
         occurrences all number
    7
    0
    23
    21
    2
    1
    7
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    Hepatobiliary disorders
    Liver disorder
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    2
    0
    1
    0
    0
    0
    Night sweats
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Skin fissures
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Rash
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    2 / 19 (10.53%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    1 / 20 (5.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    3
    0
    1
    1
    0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Back pain
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 11 (9.09%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    Pain in extremity
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    2 / 20 (10.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    1
    Dehydration
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    2 / 20 (10.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
    0 / 19 (0.00%)
    2 / 20 (10.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    1
    Hyperglycaemia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    1
    0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    2 / 19 (10.53%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    Infections and infestations
    Cystitis
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Influenza
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 19 (5.26%)
    2 / 20 (10.00%)
    1 / 23 (4.35%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    1
    Oral bacterial infection
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 11 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    1 / 20 (5.00%)
    0 / 23 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 11 (0.00%)
    1 / 19 (5.26%)
    0 / 19 (0.00%)
    0 / 19 (0.00%)
    0 / 20 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Jan 2010
    Amendment 01: Per request of the United States Food and Drug Administration (US FDA), participants in Parts I and V of the study (ages 12-17 years) were to have additional blood pressure monitoring prior to, during and following the fosaprepitant infusion, as well as serum electrolytes including sodium, potassium, magnesium, chloride, bicarbonate, total calcium, ionized calcium, and albumin collected prior to the initiation of chemotherapy; Parts III, IV, and V would not be started until data from an additional non-clinical study in juvenile animals were available, in addition to waiting until data from Part I were available. Another main change was the sample size for Part I was increased by 5 participants to increase the exposure database in participants 12-17 years of age.
    09 Nov 2011
    Amendment 02: Per request of the US FDA, the age range of participants in Parts II, III, and IV was expanded to include participants from birth to 6 months old; also, the PK of IV dexamethasone was to be evaluated as part of an antiemetic regimen both with and without concomitant administration of aprepitant in participants birth to 17 years of age, as well as part of an antiemetic regimen with concomitant administration of single IV dose of fosaprepitant in participants >6 months of age. Other main changes were: a change in dosing recommendation in participants <12 years of age was implemented from body surface area (BSA)-based dosing to weight-based dosing; Part V was changed from evaluating the safety/exploratory efficacy and PK of an IV fosaprepitant/oral aprepitant regimen to a single IV dose of fosaprepitant equivalent to 150 mg in participants 6 months to <12 years of age.
    11 Jun 2012
    Amendment 03: Per request of the US FDA, due to changes in the ondansetron label, expanded safety monitoring was implemented to include additional vital sign and electrolyte monitoring in all participants receiving ondansetron and post dose electrocardiogram (ECG) for those participants with baseline electrolyte abnormalities. Other main changes include: change in the oral aprepitant dosing regimen in participants birth to <4 months of age; and remove the requirement to obtain dexamethasone PK in participants >1 year old.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    20 Jan 2014
    Study terminated early prior to completing targeted enrollment of participants <6 months of age due to recruitment challenges.
    -

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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