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    Clinical Trial Results:
    A Phase 1/2, Multicenter, Open-Label, Dose-Finding Study To Assess The Safety, Tolerability, And Preliminary Efficacy Of Weekly Nab®-Paclitaxel In Pediatric Patients With Recurrent Or Refractory Solid Tumors

    Summary
    EudraCT number
    		 2013-000144-26
    Trial protocol
    		 IT   GB   FR   ES   Outside EU/EEA  
    Global end of trial date
    06 Nov 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 May 2019
    First version publication date
    19 May 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ABI-007-PST-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01962103
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Celgene Corporation
    Sponsor organisation address
    86 Morris Avenue, Summit, United States, 07901
    Public contact
    Clinical Trial Disclosure, Celgene Corporation, 01 888-260-1599, ClinicalTrialDisclosure@Celgene.com
    Scientific contact
    Ileana Elias, MD, Celgene Corporation, 01 647-968-4300, ILElias@celgene.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001308-PIP01-12
    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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Nov 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Nov 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Phase 1 portion: To determine the pediatric maximum tolerated dose (MTD)/ pediatric recommended Phase 2 dose (RP2D), safety and tolerability Phase 2 portion: To characterize antitumor activity at RP2D assessed by overall response rate (ORR)
    Protection of trial subjects
    Patient Confidentiality, Personal Data Protection, Archiving of Essential Documents
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Dec 2013
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 1 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 5
    Country: Number of subjects enrolled
    Canada: 4
    Country: Number of subjects enrolled
    France: 17
    Country: Number of subjects enrolled
    Italy: 34
    Country: Number of subjects enrolled
    Spain: 31
    Country: Number of subjects enrolled
    Switzerland: 5
    Country: Number of subjects enrolled
    United Kingdom: 11
    Worldwide total number of subjects
    107
    EEA total number of subjects
    93
    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)
    1
    Children (2-11 years)
    54
    Adolescents (12-17 years)
    49
    Adults (18-64 years)
    3
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 20 sites from the following countries enrolled subjects from: Canada, France, Italy, Spain, Switzerland, United Kingdom, and the United States.

    Pre-assignment
    Screening details
    		 Sixty-five subjects were included in the Phase 1 enrolled population, and 64 enrolled subjects received at least 1 dose of study drug and were included in the safety population, noted below. Forty-two subjects were included in the Phase 2 enrolled and safety populations.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Phase 1 was a rolling-6, dose-finding structure.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Phase 1: Nab-Paclitaxel 120 mg/m^2
    Arm description
    		 nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D).
    Arm type
    		 Experimental

    Investigational medicinal product name
    nab-Paclitaxel
    Investigational medicinal product code
    Other name
    Abraxane
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    nab-paclitaxel 120 mg/m^2 by IV infusion on Days 1, 8 and 15 of each 28-day cycle

    Arm title
    		 Phase 1: Nab-Paclitaxel 150 mg/m^2
    Arm description
    		 nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nab-Paclitaxel
    Investigational medicinal product code
    Other name
    Abraxane
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    nab-paclitaxel 150 mg/m^2 by IV infusion on Days 1, 8 and 15 of each 28-day cycle

    Arm title
    		 Phase 1: Nab-Paclitaxel 180 mg/m^2
    Arm description
    		 nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nab-Paclitaxel
    Investigational medicinal product code
    Other name
    Abraxane
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    nab-paclitaxel 180 mg/m^2 by IV infusion on Days 1, 8 and 15 of each 28-day cycle

    Arm title
    		 Phase 1: Nab-Paclitaxel 210 mg/m^2
    Arm description
    		 nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nab-Paclitaxel
    Investigational medicinal product code
    Other name
    Abraxane
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    nab-paclitaxel 210 mg/m^2 by IV infusion on Days 1, 8 and 15 of each 28-day cycle

    Arm title
    		 Phase 1: Nab-Paclitaxel 240 mg/m^2
    Arm description
    		 nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nab-Paclitaxel
    Investigational medicinal product code
    Other name
    Abraxane
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    nab-paclitaxel 240 mg/m^2 by IV infusion on Days 1, 8 and 15 of each 28-day cycle

    Arm title
    		 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm description
    		 nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nab-Paclitaxel
    Investigational medicinal product code
    Other name
    Abraxane
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    nab-paclitaxel 270 mg/m^2 by IV infusion on Days 1, 8 and 15 of each 28-day cycle

    Arm title
    		 Phase 2: Ewing's Sarcoma
    Arm description
    		 Subjects with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in subjects weighing > 10 kg and 11.5 mg/kg in subjects weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nab-Paclitaxel
    Investigational medicinal product code
    Other name
    Abraxane
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    nab-paclitaxel 240 mg/m^2 by IV infusion on Days 1, 8 and 15 of each 28-day cycle

    Arm title
    		 Phase 2: Neuroblastoma
    Arm description
    		 Subjects with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in subjects weighing > 10 kg and 11.5 mg/kg in subjects weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nab-Paclitaxel
    Investigational medicinal product code
    Other name
    Abraxane
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    nab-paclitaxel 240 mg/m^2 by IV infusion on Days 1, 8 and 15 of each 28-day cycle

    Arm title
    		 Phase 2: Rhabdomyosarcoma
    Arm description
    		 Subjects with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in subjects weighing > 10 kg and 11.5 mg/kg in subjects weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nab-Paclitaxel
    Investigational medicinal product code
    Other name
    Abraxane
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    nab-paclitaxel 240 mg/m^2 by IV infusion on Days 1, 8 and 15 of each 28-day cycle

    Number of subjects in period 1 [1]
    		Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2 Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma
    Started
    16
    8
    14
    11
    8
    7
    14
    14
    14
    Completed
    2
    1
    3
    6
    0
    1
    2
    4
    1
    Not completed
    14
    7
    11
    5
    8
    6
    12
    10
    13
         Death
    14
    7
    11
    5
    8
    4
    11
    10
    12
         Withdrawal by Parent/Guardian
    -
    -
    -
    -
    -
    -
    -
    -
    1
         Lost to follow-up
    -
    -
    -
    -
    -
    1
    1
    -
    -
         Other, Not Specified
    -
    -
    -
    -
    -
    1
    -
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: A total of 107 subjects were included in the enrolled population, and only 106 enrolled subjects received at least 1 dose of study drug.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Phase 1: Nab-Paclitaxel 120 mg/m^2
    Reporting group description
    		 nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D).

    Reporting group title
    Phase 1: Nab-Paclitaxel 150 mg/m^2
    Reporting group description
    		 nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-Paclitaxel 180 mg/m^2
    Reporting group description
    		 nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-Paclitaxel 210 mg/m^2
    Reporting group description
    		 nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-Paclitaxel 240 mg/m^2
    Reporting group description
    		 nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-Paclitaxel 270 mg/m^2
    Reporting group description
    		 nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 2: Ewing's Sarcoma
    Reporting group description
    		 Subjects with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in subjects weighing > 10 kg and 11.5 mg/kg in subjects weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.

    Reporting group title
    Phase 2: Neuroblastoma
    Reporting group description
    		 Subjects with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in subjects weighing > 10 kg and 11.5 mg/kg in subjects weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.

    Reporting group title
    Phase 2: Rhabdomyosarcoma
    Reporting group description
    		 Subjects with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in subjects weighing > 10 kg and 11.5 mg/kg in subjects weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.

    Reporting group values
    		 Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2 Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma Total
    Number of subjects
    		 16 8 14 11 8 7 14 14 14 106
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 11.7 ± 3.32 12.1 ± 5.84 10.2 ± 4.64 10.2 ± 5.36 11.6 ± 4.63 12.1 ± 2.97 10.1 ± 4.63 7.1 ± 3.42 12.4 ± 6.42 -
    Sex: Female, Male
    Units: Subjects
        Female
    		 9 4 9 7 1 3 6 5 9 53
        Male
    		 7 4 5 4 7 4 8 9 5 53
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 2 3 1 1 3 0 0 2 5 17
        Not Hispanic or Latino
    		 6 5 7 10 5 5 11 8 8 65
        Unknown or Not Reported
    		 8 0 6 0 0 2 3 4 1 24
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 11 8 9 9 8 5 11 11 12 84
        Not Collected or Reported
    		 5 0 5 0 0 1 3 3 1 18
        Other, Not Specified
    		 0 0 0 2 0 1 0 0 0 3
        Black or African American
    		 0 0 0 0 0 0 0 0 1 1
    Subjects With Any Prior Cancer Treatment
    Units: Subjects
        Any Prior Cancer Treatment
    		 16 8 14 11 8 7 14 14 14 106
    Number of Prior Systemic Anticancer Regimens Received
    Units: systemic anticancer regimens
        arithmetic mean (standard deviation)
    		 3.69 ± 1.815 3.25 ± 1.832 3.64 ± 1.946 3.64 ± 2.461 3.00 ± 1.309 3.00 ± 0.816 2.50 ± 0.519 2.14 ± 0.663 2.21 ± 0.579 -

    End points

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    End points reporting groups
    Reporting group title
    Phase 1: Nab-Paclitaxel 120 mg/m^2
    Reporting group description
    		 nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D).

    Reporting group title
    Phase 1: Nab-Paclitaxel 150 mg/m^2
    Reporting group description
    		 nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-Paclitaxel 180 mg/m^2
    Reporting group description
    		 nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-Paclitaxel 210 mg/m^2
    Reporting group description
    		 nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-Paclitaxel 240 mg/m^2
    Reporting group description
    		 nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-Paclitaxel 270 mg/m^2
    Reporting group description
    		 nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 2: Ewing's Sarcoma
    Reporting group description
    		 Subjects with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in subjects weighing > 10 kg and 11.5 mg/kg in subjects weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.

    Reporting group title
    Phase 2: Neuroblastoma
    Reporting group description
    		 Subjects with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in subjects weighing > 10 kg and 11.5 mg/kg in subjects weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.

    Reporting group title
    Phase 2: Rhabdomyosarcoma
    Reporting group description
    		 Subjects with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in subjects weighing > 10 kg and 11.5 mg/kg in subjects weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.

    Subject analysis set title
    Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 120 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the Phase 1: Nab-Paclitaxel 120 mg/m^2 reporting group who received at least one dose of nab-paclitaxel and had evaluable concentration data.

    Subject analysis set title
    Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 150 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the Phase 1: Nab-Paclitaxel 150 mg/m^2 reporting group who received at least one dose of nab-paclitaxel and had evaluable concentration data.

    Subject analysis set title
    Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 180 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the Phase 1: Nab-Paclitaxel 180 mg/m^2 reporting group who received at least one dose of nab-paclitaxel and had evaluable concentration data.

    Subject analysis set title
    Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 210 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the Phase 1: Nab-Paclitaxel 210 mg/m^2 reporting group who received at least one dose of nab-paclitaxel and had evaluable concentration data.

    Subject analysis set title
    Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 240 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the Phase 1: Nab-Paclitaxel 240 mg/m^2 reporting group who received at least one dose of nab-paclitaxel and had evaluable concentration data.

    Subject analysis set title
    Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 270 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the Phase 1: Nab-Paclitaxel 270 mg/m^2 reporting group who received at least one dose of nab-paclitaxel and had evaluable concentration data.

    Subject analysis set title
    Pharmacokinetic Population
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects who received at least one dose of nab-paclitaxel and had evaluable concentration data.

    Subject analysis set title
    Dose Determining Set: Phase 1: Nab-Paclitaxel 120 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All Phase 1 subjects in the Phase 1: Nab-Paclitaxel 120 mg/m^2 reporting group who received all 3 weekly doses of nab-paclitaxel at the cohort planned dose during Cycle 1 and had adequate safety assessments during the DLT assessment period or experienced a DLT. The DDS did not include subjects who were enrolled at each dose once the dose had been determined to be safe.

    Subject analysis set title
    Dose Determining Set: Phase 1: Nab-Paclitaxel 150 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All Phase 1 subjects in the Phase 1: Nab-Paclitaxel 150 mg/m^2 reporting group who received all 3 weekly doses of nab-paclitaxel at the cohort planned dose during Cycle 1 and had adequate safety assessments during the DLT assessment period or experienced a DLT. The DDS did not include subjects who were enrolled at each dose once the dose had been determined to be safe.

    Subject analysis set title
    Dose Determining Set: Phase 1: Nab-Paclitaxel 180 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All Phase 1 subjects in the Phase 1: Nab-Paclitaxel 180 mg/m^2 reporting group who received all 3 weekly doses of nab-paclitaxel at the cohort planned dose during Cycle 1 and had adequate safety assessments during the DLT assessment period or experienced a DLT. The DDS did not include subjects who were enrolled at each dose once the dose had been determined to be safe.

    Subject analysis set title
    Dose Determining Set: Phase 1: Nab-Paclitaxel 210 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All Phase 1 subjects in the Phase 1: Nab-Paclitaxel 210 mg/m^2 reporting group who received all 3 weekly doses of nab-paclitaxel at the cohort planned dose during Cycle 1 and had adequate safety assessments during the DLT assessment period or experienced a DLT. The DDS did not include subjects who were enrolled at each dose once the dose had been determined to be safe.

    Subject analysis set title
    Dose Determining Set: Phase 1: Nab-Paclitaxel 240 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All Phase 1 subjects in the Phase 1: Nab-Paclitaxel 240 mg/m^2 reporting group who received all 3 weekly doses of nab-paclitaxel at the cohort planned dose during Cycle 1 and had adequate safety assessments during the DLT assessment period or experienced a DLT. The DDS did not include subjects who were enrolled at each dose once the dose had been determined to be safe.

    Subject analysis set title
    Dose Determining Set: Phase 1: Nab-Paclitaxel 270 mg/m^2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All Phase 1 subjects in the Phase 1: Nab-Paclitaxel 270 mg/m^2 reporting group who received all 3 weekly doses of nab-paclitaxel at the cohort planned dose during Cycle 1 and had adequate safety assessments during the DLT assessment period or experienced a DLT. The DDS did not include subjects who were enrolled at each dose once the dose had been determined to be safe.

    Subject analysis set title
    Efficacy Evaluable Population: Phase 2: Ewing's Sarcoma
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects in the Phase 2: Ewing's Sarcoma reporting group who met eligibility criteria for Phase 2, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.

    Subject analysis set title
    Efficacy Evaluable Population: Phase 2: Neuroblastoma
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects in the Phase 2: Neuroblastoma reporting group who met eligibility criteria for Phase 2, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.

    Subject analysis set title
    Efficacy Evaluable Population: Phase 2: Rhabdomyosarcoma
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects in the Phase 2: Rhabdomyosarcoma reporting group who met eligibility criteria for Phase 2, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.

    Subject analysis set title
    Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 120 mg/
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects in the Phase 1: Nab-Paclitaxel 120 mg/m^2 reporting group who met eligibility criteria for Phase 1, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.

    Subject analysis set title
    Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 150 mg/
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects in the Phase 1: Nab-Paclitaxel 150 mg/m^2 reporting group who met eligibility criteria for Phase 1, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.

    Subject analysis set title
    Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 180 mg/
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects in the Phase 1: Nab-Paclitaxel 180 mg/m^2 reporting group who met eligibility criteria for Phase 1, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.

    Subject analysis set title
    Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 210 mg/
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects in the Phase 1: Nab-Paclitaxel 210 mg/m^2 reporting group who met eligibility criteria for Phase 1, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.

    Subject analysis set title
    Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 240 mg/
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects in the Phase 1: Nab-Paclitaxel 240 mg/m^2 reporting group who met eligibility criteria for Phase 1, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.

    Subject analysis set title
    Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 270 mg/
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects in the Phase 1: Nab-Paclitaxel 270 mg/m^2 reporting group who met eligibility criteria for Phase 1, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.

    Primary: Phase 1: Number of Subjects With Dose Limiting Toxicities (DLTs)

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    End point title
    		 Phase 1: Number of Subjects With Dose Limiting Toxicities (DLTs) [1]
    End point description
    A DLT = investigational product (IP) related adverse event occurring during the DLT assessment period that led to treatment discontinuation or met one of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE) Grade (Gr) 3 or 4 nonhematologic toxicity (excluding transient transaminitis); CTCAE Gr 3 or 4 nausea or vomiting that persisted > 5 days despite maximal anti-emetic treatment; CTCAE Gr 4 thrombocytopenia or anemia that persisted > 7 days or required transfusion > 7 days; CTCAE Gr 3 thrombocytopenia with bleeding; CTCAE Gr 4 uncomplicated neutropenia lasting > 7 days; Febrile neutropenia with confirmed bacterial infection; CTCAE Gr 3 hematologic toxicity requiring treatment delay > 21 days. Use of "..." in the table rows signifies the continuation of row title per the above list.
    End point type
    Primary
    End point timeframe
    DLT assessment period: For subjects > 10 kg: the first 28-day cycle including Cycle 2 Day 1 predose evaluations; for subjects ≤ 10 kg: the first two 28-day cycles including Cycle 3 Day 1 predose evaluations
    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: Endpoint data presented for Phase 1 only, per protocol.
    End point values
    		 Dose Determining Set: Phase 1: Nab-Paclitaxel 120 mg/m^2 Dose Determining Set: Phase 1: Nab-Paclitaxel 150 mg/m^2 Dose Determining Set: Phase 1: Nab-Paclitaxel 180 mg/m^2 Dose Determining Set: Phase 1: Nab-Paclitaxel 210 mg/m^2 Dose Determining Set: Phase 1: Nab-Paclitaxel 240 mg/m^2 Dose Determining Set: Phase 1: Nab-Paclitaxel 270 mg/m^2
    Number of subjects analysed
    6
    6
    6
    6
    6
    7
    Units: subjects
        At least 1 DLT
    1
    0
    0
    0
    0
    1
        Gr 3/4 Nonhematologic Toxicity...
    1
    0
    0
    0
    0
    0
        Gr 3/4 Nausea or Vomiting Persisting >5 days...
    0
    0
    0
    0
    0
    0
        Gr 4 Thrombocytopenia/Anemia Persisting >7 days...
    0
    0
    0
    0
    0
    0
        Gr 3 Thrombocytopenia with Bleeding
    0
    0
    0
    0
    0
    0
        Gr 4 Uncomplicated Neutropenia Lasting >7 days
    0
    0
    0
    0
    0
    1
        Febrile Neutropenia+Confirmed Bacterial Infection
    0
    0
    0
    0
    0
    0
        Gr3 Hematologic Toxicity Requiring Tx Delay...
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    		 Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) [2] [3]
    End point description
    An adverse event (AE) was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE (SAE) is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of an AE was graded according to the CTCAE, Version 4.0. Safety Population: all subjects who took at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively. Subjects were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Endpoint data presented for Phase 1 only, per protocol.
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint data presented for Phase 1 and Phase 2 presented separately.
    End point values
    		 Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Number of subjects analysed
    16
    8
    14
    11
    8
    7
    Units: subjects
        TEAE
    16
    8
    14
    11
    8
    7
        Treatment-related (TR) TEAE
    14
    8
    12
    11
    7
    7
        Grade 3 or 4 TEAE
    13
    8
    10
    10
    8
    7
        TR Grade 3 or 4 TEAE
    9
    7
    7
    9
    7
    7
        Serious TEAE
    10
    7
    6
    5
    3
    4
        TR Serious TEAE
    1
    4
    4
    2
    1
    3
        TEAE Leading to IP Discontinuation
    4
    0
    2
    1
    2
    2
        TR TEAE Leading to IP Discontinuation
    1
    0
    0
    1
    2
    2
        TEAE Leading to Dose Reduction
    0
    1
    2
    1
    3
    3
        TR TEAE Leading to Dose Reduction
    0
    1
    2
    1
    3
    3
        TEAE Leading to IP Interruption
    2
    2
    3
    4
    3
    2
        TR TEAE Leading to IP Interruption
    0
    2
    1
    3
    3
    2
        TEAE Leading to Death
    2
    1
    0
    0
    1
    1
        TR TEAE Leading to Death
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Phase 2: Overall Response Rate (ORR)

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    End point title
    		 Phase 2: Overall Response Rate (ORR) [4]
    End point description
    Overall response rate was defined as the percentage of subjects who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. (For Phase 2 neuroblastoma subjects who had both RECIST and Curie Score tumor evaluations, both tumor response results were considered and an overall response was derived.) Confidence interval was obtained using the Clopper-Pearson method.
    End point type
    Primary
    End point timeframe
    Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).
    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: Endpoint data presented for Phase 1 and Phase 2 separately.
    End point values
    		 Efficacy Evaluable Population: Phase 2: Ewing's Sarcoma Efficacy Evaluable Population: Phase 2: Neuroblastoma Efficacy Evaluable Population: Phase 2: Rhabdomyosarcoma
    Number of subjects analysed
    13
    14
    14
    Units: percentage of subjects
        number (confidence interval 95%)
    0 (0.0 to 24.7)
    0 (0.0 to 23.2)
    7.1 (0.2 to 33.9)
    No statistical analyses for this end point

    Secondary: Phase 1: ORR

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    End point title
    		 Phase 1: ORR
    End point description
    Overall response rate was defined as the percentage of subjects who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met) using RECIST version 1.1 guidelines over the total number of subjects available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
    End point type
    Secondary
    End point timeframe
    Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively.
    End point values
    		 Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 120 mg/ Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 150 mg/ Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 180 mg/ Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 210 mg/ Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 240 mg/ Efficacy Evaluable Population: Phase 1: Nab-Paclitaxel 270 mg/
    Number of subjects analysed
    14
    8
    12
    10
    8
    7
    Units: percentage of subjects
        number (confidence interval 95%)
    0 (0.0 to 23.2)
    0 (0.0 to 36.9)
    0 (0.0 to 26.5)
    0 (0.0 to 30.8)
    12.5 (0.3 to 52.7)
    14.3 (0.4 to 57.9)
    No statistical analyses for this end point

    Secondary: Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax)

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    End point title
    		 Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax)
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 120 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 150 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 180 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 210 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 240 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 270 mg/m^2
    Number of subjects analysed
    13
    7
    12
    9
    7
    6
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    3488 ± 73.7
    5468 ± 38.0
    5597 ± 33.4
    5616 ± 63.9
    7831 ± 23.1
    8078 ± 41.5
    No statistical analyses for this end point

    Secondary: Phase 1: Cmax - Dose-Normalized

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    End point title
    		 Phase 1: Cmax - Dose-Normalized
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 120 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 150 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 180 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 210 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 240 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 270 mg/m^2
    Number of subjects analysed
    13
    7
    12
    9
    7
    6
    Units: ng/mL/[mg]
        geometric mean (geometric coefficient of variation)
    23.3 ± 87.5
    25.4 ± 46.6
    27.3 ± 47.3
    23.2 ± 80.3
    28.2 ± 48.7
    21.0 ± 46.6
    No statistical analyses for this end point

    Secondary: Phase 1: Area Under the Plasma Concentration-Time Curve (AUC)

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    End point title
    		 Phase 1: Area Under the Plasma Concentration-Time Curve (AUC)
    End point description
    Measurements include: AUC from time zero to the last measurable concentration (AUCt), AUC from time zero to 24 hours (AUC24), and AUC from time zero to infinity (AUCinf).
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 120 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 150 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 180 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 210 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 240 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 270 mg/m^2
    Number of subjects analysed
    13 [5]
    7 [6]
    12 [7]
    9 [8]
    7 [9]
    6 [10]
    Units: ng*h/mL
    geometric mean (geometric coefficient of variation)
        AUCt; n=13, 7, 12, 9, 7, 6
    7844 ± 73.4
    10374 ± 91.8
    9690 ± 37.1
    11817 ± 64.0
    12706 ± 29.2
    11245 ± 22.6
        AUC24; n=13, 7, 12, 8, 7, 6
    6392 ± 79.0
    8944 ± 85.9
    8365 ± 37.7
    10932 ± 66.3
    11167 ± 27.4
    9768 ± 20.7
        AUCinf; n=9, 6, 10, 6, 6, 5
    8867 ± 85.4
    11992 ± 99.8
    10087 ± 38.4
    14361 ± 72.1
    14242 ± 29.2
    12424 ± 28.5
    Notes
    [5] - n=subjects with an evaluable assessment for given measure
    [6] - n=subjects with an evaluable assessment for given measure
    [7] - n=subjects with an evaluable assessment for given measure
    [8] - n=subjects with an evaluable assessment for given measure
    [9] - n=subjects with an evaluable assessment for given measure
    [10] - n=subjects with an evaluable assessment for given measure
    No statistical analyses for this end point

    Secondary: Phase 1: AUC - Dose-Normalized

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    End point title
    		 Phase 1: AUC - Dose-Normalized
    End point description
    Measurements include: AUC24 and AUCinf.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 120 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 150 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 180 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 210 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 240 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 270 mg/m^2
    Number of subjects analysed
    13 [11]
    7 [12]
    12 [13]
    8 [14]
    7 [15]
    6 [16]
    Units: ng*h/mL/[mg]
    geometric mean (geometric coefficient of variation)
        AUC24; n=13, 7, 12, 8, 7, 6
    42.7 ± 77.4
    41.6 ± 87.0
    40.8 ± 39.7
    43.3 ± 63.6
    40.2 ± 65.4
    25.4 ± 26.1
        AUCinf; n=9, 6, 10, 6, 6, 5
    62.0 ± 75.7
    49.2 ± 101
    47.8 ± 39.8
    64.8 ± 25.4
    52.3 ± 67.4
    31.3 ± 34.9
    Notes
    [11] - n=subjects with an evaluable assessment for given measure
    [12] - n=subjects with an evaluable assessment for given measure
    [13] - n=subjects with an evaluable assessment for given measure
    [14] - n=subjects with an evaluable assessment for given measure
    [15] - n=subjects with an evaluable assessment for given measure
    [16] - n=subjects with an evaluable assessment for given measure
    No statistical analyses for this end point

    Secondary: Phase 1: Clearance (CL)

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    End point title
    		 Phase 1: Clearance (CL)
    End point description
    Measurement of renal clearance from the body.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 120 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 150 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 180 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 210 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 240 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 270 mg/m^2
    Number of subjects analysed
    9
    6
    10
    6
    6
    5
    Units: L/h
        geometric mean (geometric coefficient of variation)
    16.1 ± 75.6
    20.3 ± 101
    20.9 ± 39.9
    15.4 ± 25.4
    19.1 ± 67.4
    31.9 ± 35.0
    No statistical analyses for this end point

    Secondary: Phase 1: CL - Body Surface Area (BSA)-Normalized

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    End point title
    		 Phase 1: CL - Body Surface Area (BSA)-Normalized
    End point description
    Measurement of renal clearance from the body.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 120 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 150 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 180 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 210 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 240 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 270 mg/m^2
    Number of subjects analysed
    9
    6
    10
    6
    6
    5
    Units: L/h/m^2
        geometric mean (geometric coefficient of variation)
    13.5 ± 85.1
    12.5 ± 99.3
    17.8 ± 38.3
    14.6 ± 72.3
    16.7 ± 29.2
    21.8 ± 28.4
    No statistical analyses for this end point

    Secondary: Phase 1: Volume of Distribution (Vss)

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    End point title
    		 Phase 1: Volume of Distribution (Vss)
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 120 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 150 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 180 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 210 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 240 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 270 mg/m^2
    Number of subjects analysed
    9
    6
    10
    6
    6
    5
    Units: liters
        geometric mean (geometric coefficient of variation)
    127 ± 145
    266 ± 78.3
    146 ± 106
    89.8 ± 45.1
    175 ± 117
    446 ± 17.6
    No statistical analyses for this end point

    Secondary: Phase 1: Vss - BSA-Normalized

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    End point title
    		 Phase 1: Vss - BSA-Normalized
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 120 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 150 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 180 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 210 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 240 mg/m^2 Pharmacokinetic Population: Phase 1: Nab-Paclitaxel 270 mg/m^2
    Number of subjects analysed
    9
    6
    10
    6
    6
    5
    Units: L/m^2
        geometric mean (geometric coefficient of variation)
    106 ± 95.3
    164 ± 78.4
    124 ± 82.8
    84.9 ± 49.7
    154 ± 56.5
    304 ± 29.0
    No statistical analyses for this end point

    Secondary: Phase 1 and 2 Population PK: Maximum Elimination Rate From the Central Compartment (VMEL)

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    End point title
    		 Phase 1 and 2 Population PK: Maximum Elimination Rate From the Central Compartment (VMEL)
    End point description
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for VMEL was 1.12.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population
    Number of subjects analysed
    106
    Units: μg/h
        number (not applicable)
    31983
    No statistical analyses for this end point

    Secondary: Phase 1 and 2 Population PK: Volume of Distribution of the Central Compartment (V1)

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    End point title
    		 Phase 1 and 2 Population PK: Volume of Distribution of the Central Compartment (V1)
    End point description
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V1 was 0.888.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population
    Number of subjects analysed
    106
    Units: liters
        number (not applicable)
    11.8
    No statistical analyses for this end point

    Secondary: Phase 1 and 2 Population PK: Concentration in the Central Compartment at 50% of VMEL (KMEL)

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    End point title
    		 Phase 1 and 2 Population PK: Concentration in the Central Compartment at 50% of VMEL (KMEL)
    End point description
    Population PK analysis was performed using nonlinear mixed effect modeling.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population
    Number of subjects analysed
    106
    Units: μg/L
        number (not applicable)
    951
    No statistical analyses for this end point

    Secondary: Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the First Peripheral Compartment (Q2)

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    End point title
    		 Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the First Peripheral Compartment (Q2)
    End point description
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q2 was 1.12.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population
    Number of subjects analysed
    106
    Units: L/h
        number (not applicable)
    22.4
    No statistical analyses for this end point

    Secondary: Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the Second Peripheral Compartment (Q3)

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    End point title
    		 Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the Second Peripheral Compartment (Q3)
    End point description
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q3 was 1.12.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population
    Number of subjects analysed
    106
    Units: L/h
        number (not applicable)
    34.8
    No statistical analyses for this end point

    Secondary: Phase 1 and 2 Population PK: Volume of Distribution of the First Peripheral Compartment (V2)

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    End point title
    		 Phase 1 and 2 Population PK: Volume of Distribution of the First Peripheral Compartment (V2)
    End point description
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V2 was 0.888.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population
    Number of subjects analysed
    106
    Units: liters
        number (not applicable)
    545
    No statistical analyses for this end point

    Secondary: Phase 1 and 2 Population PK: Volume of Distribution of the Second Peripheral Compartment (V3)

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    End point title
    		 Phase 1 and 2 Population PK: Volume of Distribution of the Second Peripheral Compartment (V3)
    End point description
    Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V3 was 0.888.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Subjects ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Subjects < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
    End point values
    		 Pharmacokinetic Population
    Number of subjects analysed
    106
    Units: liters
        number (not applicable)
    45.3
    No statistical analyses for this end point

    Secondary: Phase 2: Duration of Response (DOR)

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    End point title
    		 Phase 2: Duration of Response (DOR)
    End point description
    Duration of response was defined as the time from the date of the first response (CR/PR, using RECIST version 1.1 guidelines) to disease progression for subjects with a confirmed CR or PR. Subjects who did not have disease progression or had not died were censored at the time of their last disease assessment or at time of start of new anticancer therapy, whichever occurred first. (For Phase 2 neuroblastoma subjects who had both RECIST version 1.1 and Curie Score tumor evaluations, both tumor responses results were considered and an overall response was derived.)
    End point type
    Secondary
    End point timeframe
    Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Subjects were followed until disease progression (if applicable) up to a maximum of 100.3 weeks.
    End point values
    		 Efficacy Evaluable Population: Phase 2: Ewing's Sarcoma Efficacy Evaluable Population: Phase 2: Neuroblastoma Efficacy Evaluable Population: Phase 2: Rhabdomyosarcoma
    Number of subjects analysed
    0 [17]
    0 [18]
    1
    Units: weeks
        median (full range (min-max))
    ( to )
    ( to )
    6.14 (6.14 to 6.14)
    Notes
    [17] - no response in the Ewing's Sarcoma group
    [18] - no response in the Neuroblastoma group
    No statistical analyses for this end point

    Secondary: Phase 2: Disease Control Rate (DCR)

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    End point title
    		 Phase 2: Disease Control Rate (DCR)
    End point description
    Disease control rate was defined as the percentage of subjects who achieved either a stable disease maintained for ≥ 16 weeks or confirmed CR (confirmed no less than 4 weeks after criteria for response were first met) or confirmed PR (confirmed no less than 4 weeks after criteria for response were first met) over the total number of subjects available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
    End point type
    Secondary
    End point timeframe
    Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).
    End point values
    		 Efficacy Evaluable Population: Phase 2: Ewing's Sarcoma Efficacy Evaluable Population: Phase 2: Neuroblastoma Efficacy Evaluable Population: Phase 2: Rhabdomyosarcoma
    Number of subjects analysed
    13
    14
    14
    Units: percentage of subjects
        number (confidence interval 95%)
    30.8 (9.1 to 61.4)
    7.1 (0.2 to 33.9)
    7.1 (0.2 to 33.9)
    No statistical analyses for this end point

    Secondary: Phase 2: Progression-Free Survival (PFS)

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    End point title
    		 Phase 2: Progression-Free Survival (PFS)
    End point description
    PFS was defined as the time from the first dose date to the start of disease progression or subject death (any cause), whichever occurred first. Disease progression was classed as either a disease progression observed as a response assessment, or a disease progression or symptomatic deterioration at treatment/study discontinuation. Subjects who did not have disease progression or had not died were censored at the last known time that the subject was progression free. Disease progression was considered according to RECIST version 1.1 for Phase 2 Ewing's sarcoma and rhabdomyosarcoma subjects. (For Phase 2 neuroblastoma subjects who had both RECIST 1.1 and Curie score tumor evaluations, both tumor responses results were considered and an overall response was derived.) Median PFS time was estimated through Kaplan-Meier methods. 95% confidence interval about the median time to PFS event was obtained using Greenwood’s method.
    End point type
    Secondary
    End point timeframe
    Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Subjects were followed until disease progression (if applicable) up to a maximum of 100.3 weeks.
    End point values
    		 Efficacy Evaluable Population: Phase 2: Ewing's Sarcoma Efficacy Evaluable Population: Phase 2: Neuroblastoma Efficacy Evaluable Population: Phase 2: Rhabdomyosarcoma
    Number of subjects analysed
    13
    14
    14
    Units: weeks
        median (confidence interval 95%)
    13 (7.4 to 16.1)
    7.4 (4.6 to 8.1)
    5.1 (2.1 to 7.9)
    No statistical analyses for this end point

    Secondary: Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 year

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    End point title
    		 Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 year
    End point description
    Overall survival was defined as the time from the first dose date to date of death (any cause). Subjects who were alive were censored at the last known time that the subject was alive.
    End point type
    Secondary
    End point timeframe
    1 year
    End point values
    		 Efficacy Evaluable Population: Phase 2: Ewing's Sarcoma Efficacy Evaluable Population: Phase 2: Neuroblastoma Efficacy Evaluable Population: Phase 2: Rhabdomyosarcoma
    Number of subjects analysed
    13
    14
    14
    Units: percentage of participants
        number (confidence interval 95%)
    27 (7 to 53)
    29 (9 to 52)
    15 (2 to 39)
    No statistical analyses for this end point

    Secondary: Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    		 Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) [19]
    End point description
    An AE was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A SAE is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of the AEs was graded according to the Common Terminology Criteria for Adverse Events, Version 4.0. Subjects were followed for 28 days after discontinuing treatment for safety and monitoring of AEs. Safety Population: all subjects who took at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Median treatment duration in Phase 2 for Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13); subjects were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint data presented for Phase 1 and Phase 2 separately.
    End point values
    		 Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma
    Number of subjects analysed
    14
    14
    14
    Units: Participants
        TEAE
    14
    14
    14
        Treatment-related (TR) TEAE
    13
    12
    12
        Grade 3 or 4 TEAE
    12
    13
    12
        TR Grade 3 or 4 TEAE
    9
    9
    10
        Serious TEAE
    6
    6
    11
        TR Serious TEAE
    2
    2
    6
        TEAE Leading to Drug Discontinuation
    3
    1
    3
        TR TEAE Leading to Drug Discontinuation
    1
    0
    3
        TEAE Leading to Dose Reduction
    4
    5
    4
        TR TEAE Leading to Dose Reduction
    4
    4
    4
        TEAE Leading to Drug Interruption
    5
    3
    4
        TR TEAE Leading to Drug Interruption
    3
    3
    2
        TEAE Leading to Death
    0
    2
    3
        TR TEAE Leading to Death
    0
    0
    0
    No statistical analyses for this end point

    Other pre-specified: Number of Subjects who Received at Least One Post-treatment Anticancer Therapy

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    End point title
    		 Number of Subjects who Received at Least One Post-treatment Anticancer Therapy
    End point description
    End point type
    Other pre-specified
    End point timeframe
    From the date of randomization to final date cut off date of 06 November 2018
    End point values
    		 Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2 Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma
    Number of subjects analysed
    16
    8
    14
    11
    8
    7
    14
    14
    14
    Units: subjects
    12
    2
    12
    10
    7
    6
    11
    9
    8
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Median treatment duration in Phase 1 = 7.0 weeks (minimum and maximum duration of 1 and 49 weeks); median treatment duration in Phase 2 per group: Ewings sarcoma = 14 weeks (3-31), neuroblastoma = 7 weeks (3-23), rhabdomyosarcoma = 5 weeks (1-13).
    Adverse event reporting additional description
    All subjects in both portions of the study were followed for 28 days after discontinuing treatment for safety and monitoring of AEs. AEs were analyzed in terms of TEAEs, which were defined as any AEs that began or worsened in severity on or after the start of study drug through 28 days after the last dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Phase 1: Nab-Paclitaxel 120 mg/m^2
    Reporting group description
    		 nab-paclitaxel 120 mg/m^2 IV on Days 1, 8 and 15 of a 28- day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-paclitaxel 150 mg/m^2
    Reporting group description
    		 nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-paclitaxel 180 mg/m2
    Reporting group description
    		 nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-paclitaxel 210 mg/m2
    Reporting group description
    		 nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-paclitaxel 240 mg/m^2
    Reporting group description
    		 nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 1: Nab-paclitaxel 270 mg/m^2
    Reporting group description
    		 nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Reporting group title
    Phase 2: Sarcoma, Neuroblastoma and Rhabdomyosarcoma
    Reporting group description
    		 Participants with Ewing's sarcoma, Neuroblastoma and Rhabdomyosarcoma received nab- paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.

    Serious adverse events
    		 Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-paclitaxel 150 mg/m^2 Phase 1: Nab-paclitaxel 180 mg/m2 Phase 1: Nab-paclitaxel 210 mg/m2 Phase 1: Nab-paclitaxel 240 mg/m^2 Phase 1: Nab-paclitaxel 270 mg/m^2 Phase 2: Sarcoma, Neuroblastoma and Rhabdomyosarcoma
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 16 (62.50%)
    7 / 8 (87.50%)
    6 / 14 (42.86%)
    5 / 11 (45.45%)
    3 / 8 (37.50%)
    4 / 7 (57.14%)
    23 / 42 (54.76%)
         number of deaths (all causes)
    2
    1
    0
    0
    1
    1
    33
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Osteosarcoma
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteosarcoma metastatic
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Refractory anaemia with an excess of blasts
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Tumour pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Hypotension
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    2 / 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
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    4 / 42 (9.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 4
    Generalised oedema
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Oedema peripheral
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Pyrexia
         subjects affected / exposed
    0 / 16 (0.00%)
    3 / 8 (37.50%)
    2 / 14 (14.29%)
    3 / 11 (27.27%)
    1 / 8 (12.50%)
    2 / 7 (28.57%)
    6 / 42 (14.29%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 8
    5 / 6
    7 / 8
    0 / 1
    3 / 3
    7 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Hypoxia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Pleural effusion
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 3
    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
    Pneumonitis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Pneumothorax
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Respiratory failure
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Psychiatric disorders
    Restlessness
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Injury, poisoning and procedural complications
    Anaphylactic transfusion reaction
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         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
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    1 / 1
    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
    Headache
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial pressure increased
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Seizure
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Slow speech
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         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
    Somnolence
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Tremor
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         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
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    4 / 42 (9.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    3 / 3
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Neutropenia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    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
    Thrombocytopenia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 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
    Nausea
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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 / 16 (0.00%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Dermatitis bullous
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    Erythema
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         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
    Skin exfoliation
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         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
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anuria
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Urinary tract obstruction
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    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
    Bone pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         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
    Pain in extremity
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Device related infection
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         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
    Gastroenteritis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         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
    Lower respiratory tract infection bacterial
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         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
    Pneumonia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         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
    Varicella
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (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
    Hypercreatininaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    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
    Hyponatraemia
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 8 (25.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-paclitaxel 150 mg/m^2 Phase 1: Nab-paclitaxel 180 mg/m2 Phase 1: Nab-paclitaxel 210 mg/m2 Phase 1: Nab-paclitaxel 240 mg/m^2 Phase 1: Nab-paclitaxel 270 mg/m^2 Phase 2: Sarcoma, Neuroblastoma and Rhabdomyosarcoma
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    16 / 16 (100.00%)
    8 / 8 (100.00%)
    14 / 14 (100.00%)
    11 / 11 (100.00%)
    8 / 8 (100.00%)
    7 / 7 (100.00%)
    42 / 42 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    2 / 14 (14.29%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    4
    1
    0
    0
    0
    Skin papilloma
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Tumour pain
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    3 / 42 (7.14%)
         occurrences all number
    8
    1
    0
    3
    0
    1
    4
    Vascular disorders
    Hyperaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    3 / 42 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    5
    Hypertension
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    1
    Hypotension
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    2 / 14 (14.29%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    0
    Lymphoedema
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    3
    0
    0
    2
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    1 / 11 (9.09%)
    3 / 8 (37.50%)
    1 / 7 (14.29%)
    9 / 42 (21.43%)
         occurrences all number
    1
    1
    1
    1
    5
    2
    9
    Catheter site pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Face oedema
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    2
    Fatigue
         subjects affected / exposed
    3 / 16 (18.75%)
    3 / 8 (37.50%)
    4 / 14 (28.57%)
    4 / 11 (36.36%)
    2 / 8 (25.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    5
    6
    5
    8
    2
    0
    3
    General physical health deterioration
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    1
    1
    1
    0
    0
    Generalised oedema
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Malaise
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 8 (25.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 8 (25.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    3 / 16 (18.75%)
    3 / 8 (37.50%)
    2 / 14 (14.29%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    8 / 42 (19.05%)
         occurrences all number
    4
    11
    2
    1
    2
    0
    11
    Pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    6 / 16 (37.50%)
    3 / 8 (37.50%)
    5 / 14 (35.71%)
    5 / 11 (45.45%)
    4 / 8 (50.00%)
    2 / 7 (28.57%)
    14 / 42 (33.33%)
         occurrences all number
    17
    3
    8
    15
    11
    6
    26
    Xerosis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Reproductive system and breast disorders
    Genital pain
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Menstruation irregular
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Oedema genital
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 8 (25.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    1
    Scrotal oedema
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Vulvovaginal discomfort
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Cough
         subjects affected / exposed
    2 / 16 (12.50%)
    3 / 8 (37.50%)
    2 / 14 (14.29%)
    4 / 11 (36.36%)
    3 / 8 (37.50%)
    0 / 7 (0.00%)
    6 / 42 (14.29%)
         occurrences all number
    4
    8
    2
    4
    3
    0
    10
    Dysaesthesia pharynx
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Dysphonia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    Dyspnoea
         subjects affected / exposed
    3 / 16 (18.75%)
    0 / 8 (0.00%)
    2 / 14 (14.29%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    3
    0
    3
    0
    0
    0
    2
    Epistaxis
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 8 (25.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 7 (28.57%)
    5 / 42 (11.90%)
         occurrences all number
    1
    2
    1
    0
    0
    2
    8
    Haemoptysis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    Hypoxia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Lung consolidation
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    2
    0
    2
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 8 (25.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    1
    0
    Pharyngeal erythema
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 8 (25.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    3
    1
    0
    0
    0
    1
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Pleural effusion
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    2
    1
    0
    0
    0
    1
    0
    Productive cough
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    Tachypnoea
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Wheezing
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 16 (12.50%)
    3 / 8 (37.50%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    2
    3
    1
    0
    0
    0
    1
    Confusional state
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    Depression
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 8 (25.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    1
    Enuresis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    2 / 11 (18.18%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    2 / 42 (4.76%)
         occurrences all number
    1
    0
    0
    2
    0
    1
    3
    Mood altered
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Restlessness
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 16 (0.00%)
    3 / 8 (37.50%)
    1 / 14 (7.14%)
    3 / 11 (27.27%)
    1 / 8 (12.50%)
    1 / 7 (14.29%)
    2 / 42 (4.76%)
         occurrences all number
    0
    6
    1
    4
    1
    1
    5
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 8 (25.00%)
    1 / 14 (7.14%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    3 / 42 (7.14%)
         occurrences all number
    0
    4
    1
    1
    1
    0
    4
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 16 (0.00%)
    4 / 8 (50.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    9
    0
    1
    0
    0
    2
    Blood bicarbonate decreased
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Blood urea increased
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    2 / 11 (18.18%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    2
    Candida test positive
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Electroencephalogram abnormal
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    2
    Glucose urine present
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    International normalised ratio increased
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 7 (14.29%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    0
    4
    5
    2
    Platelet count decreased
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Urine output decreased
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    2 / 8 (25.00%)
    2 / 7 (28.57%)
    1 / 42 (2.38%)
         occurrences all number
    2
    0
    0
    1
    3
    3
    1
    Weight increased
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    Contusion
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Excoriation
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Fall
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    2 / 8 (25.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    Humerus fracture
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Muscle injury
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Recall phenomenon
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Scar
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    Vascular access complication
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Wound secretion
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Congenital, familial and genetic disorders
    Hydrocele
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    Cardiac disorders
    Aortic valve disease
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Palpitations
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Pericardial effusion
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    1
    0
    Sinus bradycardia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 8 (25.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    Nervous system disorders
    Depressed level of consciousness
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 8 (25.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    1
    2
    1
    0
    0
    0
    2
    Dysaesthesia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    Dysgeusia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    0
    1
    0
    2
    1
    Headache
         subjects affected / exposed
    3 / 16 (18.75%)
    2 / 8 (25.00%)
    3 / 14 (21.43%)
    2 / 11 (18.18%)
    1 / 8 (12.50%)
    1 / 7 (14.29%)
    11 / 42 (26.19%)
         occurrences all number
    4
    7
    4
    2
    1
    2
    15
    Lethargy
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    Neuralgia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    3 / 42 (7.14%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    7
    Neuropathy peripheral
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 7 (14.29%)
    1 / 42 (2.38%)
         occurrences all number
    1
    0
    0
    0
    1
    2
    1
    Peripheral motor neuropathy
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    2 / 8 (25.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    2 / 14 (14.29%)
    0 / 11 (0.00%)
    3 / 8 (37.50%)
    2 / 7 (28.57%)
    3 / 42 (7.14%)
         occurrences all number
    1
    0
    3
    0
    7
    4
    8
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Sciatica
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    4
    1
    0
    0
    0
    0
    Spinal cord compression
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    Visual field defect
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    8 / 16 (50.00%)
    6 / 8 (75.00%)
    6 / 14 (42.86%)
    5 / 11 (45.45%)
    6 / 8 (75.00%)
    6 / 7 (85.71%)
    27 / 42 (64.29%)
         occurrences all number
    17
    19
    20
    15
    13
    25
    68
    Febrile neutropenia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Leukopenia
         subjects affected / exposed
    6 / 16 (37.50%)
    1 / 8 (12.50%)
    2 / 14 (14.29%)
    5 / 11 (45.45%)
    5 / 8 (62.50%)
    3 / 7 (42.86%)
    18 / 42 (42.86%)
         occurrences all number
    22
    20
    15
    9
    38
    34
    69
    Lymphadenitis
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Lymphopenia
         subjects affected / exposed
    6 / 16 (37.50%)
    2 / 8 (25.00%)
    1 / 14 (7.14%)
    2 / 11 (18.18%)
    2 / 8 (25.00%)
    3 / 7 (42.86%)
    5 / 42 (11.90%)
         occurrences all number
    15
    5
    5
    5
    9
    27
    10
    Neutropenia
         subjects affected / exposed
    7 / 16 (43.75%)
    4 / 8 (50.00%)
    6 / 14 (42.86%)
    8 / 11 (72.73%)
    7 / 8 (87.50%)
    6 / 7 (85.71%)
    23 / 42 (54.76%)
         occurrences all number
    22
    24
    27
    33
    43
    38
    97
    Neutrophilia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 8 (25.00%)
    2 / 14 (14.29%)
    1 / 11 (9.09%)
    2 / 8 (25.00%)
    4 / 7 (57.14%)
    8 / 42 (19.05%)
         occurrences all number
    3
    4
    3
    3
    6
    11
    37
    Thrombocytosis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    3 / 42 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    4
    Ear swelling
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Vertigo
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    1 / 42 (2.38%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    1
    Eye disorders
    Diplopia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Dry eye
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Eye irritation
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Eye pain
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Eye pruritus
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Keratitis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Periorbital oedema
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    2 / 11 (18.18%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    3 / 42 (7.14%)
         occurrences all number
    0
    0
    1
    2
    0
    2
    4
    Photophobia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Vision blurred
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    5 / 42 (11.90%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    5
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    0
    Abdominal pain
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 8 (25.00%)
    3 / 14 (21.43%)
    2 / 11 (18.18%)
    3 / 8 (37.50%)
    2 / 7 (28.57%)
    6 / 42 (14.29%)
         occurrences all number
    4
    6
    3
    2
    6
    6
    9
    Abdominal pain upper
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    2 / 14 (14.29%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    2
    1
    0
    0
    0
    Anal fissure
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    Anal incontinence
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Anal inflammation
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Anorectal discomfort
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Ascites
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    4 / 16 (25.00%)
    3 / 8 (37.50%)
    3 / 14 (21.43%)
    6 / 11 (54.55%)
    2 / 8 (25.00%)
    1 / 7 (14.29%)
    10 / 42 (23.81%)
         occurrences all number
    4
    4
    4
    8
    2
    1
    12
    Diarrhoea
         subjects affected / exposed
    2 / 16 (12.50%)
    4 / 8 (50.00%)
    4 / 14 (28.57%)
    3 / 11 (27.27%)
    4 / 8 (50.00%)
    2 / 7 (28.57%)
    8 / 42 (19.05%)
         occurrences all number
    2
    8
    14
    6
    5
    7
    11
    Diarrhoea haemorrhagic
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 8 (25.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    2 / 8 (25.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    0
    5
    1
    0
    2
    0
    2
    Eructation
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Flatulence
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    2 / 14 (14.29%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    0
    Gastrointestinal pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    Haematochezia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    6 / 16 (37.50%)
    3 / 8 (37.50%)
    2 / 14 (14.29%)
    4 / 11 (36.36%)
    2 / 8 (25.00%)
    3 / 7 (42.86%)
    10 / 42 (23.81%)
         occurrences all number
    6
    9
    2
    6
    4
    6
    12
    Odynophagia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Salivary hypersecretion
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    2 / 11 (18.18%)
    1 / 8 (12.50%)
    2 / 7 (28.57%)
    8 / 42 (19.05%)
         occurrences all number
    1
    1
    0
    3
    1
    2
    9
    Toothache
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    0
    3
    1
    0
    0
    0
    2
    Vomiting
         subjects affected / exposed
    8 / 16 (50.00%)
    3 / 8 (37.50%)
    2 / 14 (14.29%)
    3 / 11 (27.27%)
    3 / 8 (37.50%)
    1 / 7 (14.29%)
    14 / 42 (33.33%)
         occurrences all number
    10
    14
    6
    6
    6
    3
    22
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    2 / 16 (12.50%)
    4 / 8 (50.00%)
    4 / 14 (28.57%)
    5 / 11 (45.45%)
    3 / 8 (37.50%)
    2 / 7 (28.57%)
    6 / 42 (14.29%)
         occurrences all number
    2
    5
    5
    9
    4
    3
    8
    Dermatitis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Dermatitis acneiform
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    Dermatitis atopic
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    2 / 11 (18.18%)
    2 / 8 (25.00%)
    2 / 7 (28.57%)
    2 / 42 (4.76%)
         occurrences all number
    0
    0
    1
    2
    2
    2
    2
    Ecchymosis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    Erythema
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    2 / 11 (18.18%)
    2 / 8 (25.00%)
    1 / 7 (14.29%)
    7 / 42 (16.67%)
         occurrences all number
    0
    1
    0
    3
    2
    1
    8
    Haemorrhage subcutaneous
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Intertrigo
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Nail bed inflammation
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Nail discolouration
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Onychoclasis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Onycholysis
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Pain of skin
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    2 / 7 (28.57%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    7
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    2 / 42 (4.76%)
         occurrences all number
    0
    2
    0
    1
    0
    3
    4
    Photosensitivity reaction
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    3 / 42 (7.14%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    3
    Pruritus
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 8 (25.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    1 / 7 (14.29%)
    2 / 42 (4.76%)
         occurrences all number
    2
    7
    0
    1
    1
    1
    2
    Pruritus generalised
         subjects affected / exposed
    3 / 16 (18.75%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    2 / 7 (28.57%)
    5 / 42 (11.90%)
         occurrences all number
    3
    0
    1
    1
    0
    2
    6
    Rash
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Rash erythematous
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    1
    5
    0
    1
    1
    Rash macular
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    3
    1
    8
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    2 / 8 (25.00%)
    1 / 7 (14.29%)
    7 / 42 (16.67%)
         occurrences all number
    0
    1
    0
    0
    5
    1
    10
    Rash papular
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    Skin exfoliation
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    2
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    2 / 8 (25.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    2
    0
    1
    3
    0
    1
    Toxic erythema of chemotherapy
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    4
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    4
    0
    0
    0
    0
    0
    Dysuria
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    Haematuria
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    1
    Ketonuria
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Pollakiuria
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Polyuria
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    Renal pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Urinary incontinence
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Urinary retention
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    1
    Urinary tract obstruction
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    1
    Urinary tract pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    2
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 8 (25.00%)
    0 / 14 (0.00%)
    4 / 11 (36.36%)
    2 / 8 (25.00%)
    2 / 7 (28.57%)
    3 / 42 (7.14%)
         occurrences all number
    1
    5
    0
    7
    3
    4
    5
    Back pain
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 8 (25.00%)
    3 / 14 (21.43%)
    0 / 11 (0.00%)
    2 / 8 (25.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    4
    3
    3
    0
    4
    0
    1
    Bone pain
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    1
    Coccydynia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Epiphysiolysis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Flank pain
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    Groin pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Joint swelling
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    Muscular weakness
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    1 / 42 (2.38%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    1
    Musculoskeletal pain
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    2
    1
    2
    1
    0
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 16 (0.00%)
    4 / 8 (50.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    4
    0
    0
    2
    0
    0
    Neck pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    2 / 16 (12.50%)
    3 / 8 (37.50%)
    2 / 14 (14.29%)
    0 / 11 (0.00%)
    3 / 8 (37.50%)
    1 / 7 (14.29%)
    17 / 42 (40.48%)
         occurrences all number
    2
    3
    2
    0
    4
    1
    23
    Pain in jaw
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Spinal pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    2
    Infections and infestations
    Bacillus bacteraemia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Cellulitis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    2
    Cystitis
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Device related infection
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    2 / 14 (14.29%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    Ear infection
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    Herpes zoster
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    Infection
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    Lung infection
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    1 / 42 (2.38%)
         occurrences all number
    0
    2
    0
    0
    0
    1
    1
    Mucosal infection
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    1
    Oropharyngeal candidiasis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Otitis externa
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Otitis media
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    Paronychia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    Rash pustular
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    2 / 14 (14.29%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    3
    3
    1
    1
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    1 / 8 (12.50%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    3
    0
    1
    1
    1
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    2 / 42 (4.76%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    Vulvitis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    0
    0
    Cachexia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Decreased appetite
         subjects affected / exposed
    3 / 16 (18.75%)
    3 / 8 (37.50%)
    5 / 14 (35.71%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    1 / 7 (14.29%)
    6 / 42 (14.29%)
         occurrences all number
    4
    4
    5
    1
    1
    3
    6
    Dehydration
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Hyperchloraemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    Hypercreatininaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    2
    6
    0
    0
    0
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    0
    0
    Hypermagnesaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Hypernatraemia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Hyperphosphataemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 16 (12.50%)
    3 / 8 (37.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    2
    7
    0
    0
    0
    0
    4
    Hypocalcaemia
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 8 (25.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    3
    9
    2
    0
    0
    0
    1
    Hypochloraemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 8 (12.50%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    1 / 16 (6.25%)
    3 / 8 (37.50%)
    2 / 14 (14.29%)
    1 / 11 (9.09%)
    1 / 8 (12.50%)
    2 / 7 (28.57%)
    5 / 42 (11.90%)
         occurrences all number
    1
    12
    2
    1
    1
    2
    5
    Hypomagnesaemia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 8 (12.50%)
    1 / 14 (7.14%)
    1 / 11 (9.09%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    2 / 42 (4.76%)
         occurrences all number
    1
    2
    1
    1
    0
    0
    4
    Hyponatraemia
         subjects affected / exposed
    1 / 16 (6.25%)
    4 / 8 (50.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    1 / 7 (14.29%)
    1 / 42 (2.38%)
         occurrences all number
    1
    13
    1
    0
    0
    1
    1
    Hypophosphataemia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 8 (0.00%)
    0 / 14 (0.00%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    1 / 42 (2.38%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    Polydipsia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 8 (0.00%)
    1 / 14 (7.14%)
    0 / 11 (0.00%)
    0 / 8 (0.00%)
    0 / 7 (0.00%)
    0 / 42 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 May 2013
    1. A global administrative change of sponsor name from ‘Abraxis BioScience, LLC, a wholly-owned subsidiary of Celgene Corporation’ to ‘Celgene Corporation’ to reflect the retirement of the legacy entity ‘Abraxis BioScience, LLC, a wholly-owned subsidiary of Celgene Corporation’ as sponsor name. 2. The addition of echocardiogram/MUGA scans for increased cardiotoxicity monitoring. 3. Modification of the schedule of events to increase the frequency of 12-lead ECG testing. 4. The addition of a 3-month washout period for HSCT to the exclusion criteria. 5. A decrease in the volume of blood drawn for PK sampling. 6. An administrative change to clarify the PK sampling requirements for samples collected up to 1 hour after the end of study drug infusion. 7. Removal of Cycle 1 Day 1 urine homovanillic acid and vanillylmandelic acid testing. 8. Clarification and updates in the statistical analysis section (eg, safety analysis). 9. An administrative change to include the use of IRT for patient enrollment • Addition of company standard language for End of Trial, overdose, Adverse Events, Serious Adverse Events, pregnancy language, site responsibilities and monitoring, and administrative procedures • Administrative changes to correct minor errors and inconsistencies within the document and/or case report forms
    12 Mar 2014
    1. In the Phase 2 portion, a change to the sample size for the Phase 2 neuroblastoma arm, and modifications of the Simon two-stage minimax design to implement acceptance rates of approximately 20% response rates for the neuroblastoma and rhabdomyosarcoma arms. 2. The addition of ≥ Grade 2 peripheral neuropathy to the exclusion criteria. 3. The addition of information concerning the use of syringe-based devices for administration of small volumes of nab-paclitaxel suspension. 4. A change from cautionary use to prohibition of concomitant medications classified as strong inducers of CYP2C8 and CYP3A4, and additional guidance on the use of strong inhibitors of the same isozymes. 5. An administrative change to the Medical Monitor title and contact information. 6. An administrative change to include the approval of nab-paclitaxel in the US and EU for the treatment of first-line metastatic pancreatic adenocarcinoma. 7. Clarification and updates to the description of the rolling-6 design for the Phase 1 portion. 8. The addition of the use of “other medically appropriate method” for LVSF assessment. 9. The addition of company standard language for the description of investigational product. 10. Clarification of permitted dose reductions from dose level -1 in the Phase 1 portion. 11. Clarification of recommendation concerning labeling of PK samples. 12. Administrative changes to clarify protocol language and provide one additional literature reference. 13. Administrative changes to correct minor formatting errors.
    11 Jun 2014
    Significant changes included in this amendment are summarized below: 1. Update to the new IND number for nab-paclitaxel for the pediatric solid tumors indication. 2. Add specific language to discontinue and not rechallenge treatment for hypersensitivity as agreed with the FDA. 3. Clarify with specific language to discontinue treatment at the third recurrence for neutropenia events as agreed with the FDA.
    25 Mar 2015
    1. Increased scope of dense PK sample collection 2. Change of the third solid tumors group in Phase (Ph) 2 from mixed tumors to Ewing’s sarcoma 3. Harmonization of sample size and Simon two-stage minimax design for the 3 groups in Ph 2 4. Updated inclusion 2 for Ph 2 requiring radiologically documented measurable disease by RECIST version 1.1 (for neuroblastoma evaluable disease by MIBG/Curie Score 5. Updated assessment of the primary endpoint ORR in the Ph 2 neuroblastoma group to use both the RECIST version 1.1 criteria and the Curie score 6. Confirmation of CR in Ph 2 neuroblastoma 7. Decreased minimum platelet level in inclusion 5 for Ph 2 with known bone marrow involvement 8. Addition of guidance on flushing the IV line following infusion of nab-paclitaxel 9. Addition of statements regarding study conduct in compliance with ICH GCPs to align with company standard protocol language 10. Clarification of Ph 1 sample size to: additional patients enrolled at dose levels evaluated as safe by the SMC. 11. Update to length of Ph 1 (from 12 months to up to 18 months) 12. Clarification of SAE reporting during the 28-day follow-up to align with updated company standard protocol language 13. Update to the description of response assessments to include that the sponsor may conduct an independent assessment of response after study completion 14. Update to inclusion 8 to align with current Celgene Standard Risk Language 15. Clarification of safety analysis:l include summarization of AEs of special interest 16. Update to treatment discontinuation information concerning the treating physician’s responsibilities 17. Update to align with company standard protocol language concerning investigator responsibilities for handling of confidential information 18. Update to align with company standard protocol language concerning publication 19. Addition of references 20. Clarification that the MIBG tumor response assessment includes a 10th segment for any soft tissue involvement
    13 Jul 2016
    Significant changes included in this amendment are summarized below: 1. Updated inclusion criterion 1b for Phase 2 to allow enrollment of patients ≥ 6 months to ≤ 24 years of age. 2. Updated inclusion criterion 2b for Phase 2 to allow enrollment of patients who have failed up to three lines of treatment. 3. Modification of exclusion criterion 7 to differentiate between autologous and allogeneic HSCT. 4. Updated assessment of the primary endpoint (ORR) in the Phase 2 neuroblastoma group using both RECIST version 1.1 criteria and the Curie score. 5. Clarification of definition of the efficacy evaluable population 6. Addition of definition of nab-paclitaxel overdose 7. Identification of the RP2D 8. Updated Phase 1 enrollment numbers 9. Allowance for the use of historical LVSF assessments and ECGs at Screening

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    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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