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    Clinical Trial Results:
    A Phase 1 Study of the TRK Inhibitor Selitrectinib (BAY 2731954) in Adult and Pediatric Subjects with Previously Treated NTRK Fusion Cancers

    Summary
    EudraCT number
    2017-004246-20
    Trial protocol
    DK   FR   DE   ES   GB   IE   IT   BE  
    Global end of trial date
    30 Jan 2023

    Results information
    Results version number
    v1(current)
    This version publication date
    30 Jul 2023
    First version publication date
    30 Jul 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20810
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03215511
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser-Wilhelm-Allee, Leverkusen, Germany, D-51368
    Public contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Jan 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Jan 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to determine the recommended dose for further study of oral selitrectinib in 2 patient groups with previously treated neurotrophic tyrosine receptor kinase (NTRK) fusion cancers defined as age 12 years and older and age <12 years. The secondary objectives of this study were: • To characterize the pharmacokinetic (PK) properties of selitrectinib. • To characterize the safety and tolerability of selitrectinib. • To assess objective response rate (ORR) according to best response by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by investigator, in patients with a documented NTRK fusion cancer previously treated with a tropomyosin receptor kinase (TRK) inhibitor. • To assess ORR according to best response by Response Assessment in Neuro-Oncology (RANO), as determined by investigator, in patients with primary central nervous system (CNS) malignancies with NTRK fusion.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects and/or their legally authorized representative. Participating subjects and/or their legally authorized representative signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    03 Jul 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Denmark: 7
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Ireland: 1
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Singapore: 2
    Country: Number of subjects enrolled
    Spain: 7
    Country: Number of subjects enrolled
    United States: 58
    Worldwide total number of subjects
    81
    EEA total number of subjects
    21
    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)
    10
    Adolescents (12-17 years)
    4
    Adults (18-64 years)
    54
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    This multinational study was conducted at 42 centers of 13 countries from 03-Jul-2017 (first patient first visit) to 30-Jan-2023 (last patient last visit)

    Pre-assignment
    Screening details
    A total of 91 patients were enrolled in the study. Of these, there were 10 screen failures, and 81 patients received at least 1 dose of study drug.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Capsule Cohort 1
    Arm description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 100 mg twice daily (BID), in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg, Twice daily (BID)

    Arm title
    Capsule Cohort 2
    Arm description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 150 mg twice daily (BID), in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg, Twice daily (BID)

    Arm title
    Capsule Cohort 3
    Arm description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 100 mg once daily (QD), in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg, Once daily (QD)

    Arm title
    Capsule Cohort 4
    Arm description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg once daily (QD), in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg, Once daily (QD)

    Arm title
    Capsule Cohort 5a
    Arm description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg QD with escalation every 14 days to 75 mg BID, in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg QD with escalation every 14 days to 75 mg BID (capsule)

    Arm title
    Capsule Cohort 5b
    Arm description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg QD with escalation every 14 days to 150 mg QD, in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg QD with escalation every 14 days to 150 mg QD

    Arm title
    Suspension Cohort 6a
    Arm description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50mg BID, in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    50mg BID (liquid suspension)

    Arm title
    Suspension Cohort 6b
    Arm description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 75mg BID, in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    75 mg BID (liquid suspension)

    Arm title
    Suspension Cohort 7a
    Arm description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50mg QD with escalation after 7 days to 50mg BID, in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    50mg QD with escalation after 7 days to 50mg BID

    Arm title
    Suspension Cohort 7b
    Arm description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50mg QD for 7 days, then 50mg BID for 7 days, then 75mg BID, in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    50mg QD for 7 days, then 50mg BID, for 7 days, then 75mg BID

    Arm title
    Pediatric Cohort 43 mg/m^2 BID
    Arm description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 43 mg/m^2 BID, in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    75 mg BID

    Arm title
    Pediatric Cohort 58 mg/m^2 BID
    Arm description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 58 mg/m^2 BID, in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg BID

    Arm title
    Pediatric Cohort 87 mg/m^2 BID
    Arm description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 87 mg/m^2 BID, in continuous 28-day cycles.
    Arm type
    Experimental

    Investigational medicinal product name
    Selitrectinib
    Investigational medicinal product code
    BAY2731954
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg BID

    Number of subjects in period 1
    Capsule Cohort 1 Capsule Cohort 2 Capsule Cohort 3 Capsule Cohort 4 Capsule Cohort 5a Capsule Cohort 5b Suspension Cohort 6a Suspension Cohort 6b Suspension Cohort 7a Suspension Cohort 7b Pediatric Cohort 43 mg/m^2 BID Pediatric Cohort 58 mg/m^2 BID Pediatric Cohort 87 mg/m^2 BID
    Started
    5
    2
    2
    8
    23
    3
    3
    4
    14
    6
    6
    4
    1
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    5
    2
    2
    8
    23
    3
    3
    4
    14
    6
    6
    4
    1
         Adverse event, serious fatal
    4
    2
    1
    7
    18
    3
    2
    2
    9
    3
    4
    2
    -
         Consent withdrawn by subject
    1
    -
    -
    1
    3
    -
    1
    1
    3
    -
    -
    -
    -
         Other
    -
    -
    1
    -
    2
    -
    -
    -
    2
    3
    2
    2
    -
         Lost to follow-up
    -
    -
    -
    -
    -
    -
    -
    1
    -
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Capsule Cohort 1
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 100 mg twice daily (BID), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 2
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 150 mg twice daily (BID), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 3
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 100 mg once daily (QD), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 4
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg once daily (QD), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 5a
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg QD with escalation every 14 days to 75 mg BID, in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 5b
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg QD with escalation every 14 days to 150 mg QD, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort 6a
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50mg BID, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort 6b
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 75mg BID, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort 7a
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50mg QD with escalation after 7 days to 50mg BID, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort 7b
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50mg QD for 7 days, then 50mg BID for 7 days, then 75mg BID, in continuous 28-day cycles.

    Reporting group title
    Pediatric Cohort 43 mg/m^2 BID
    Reporting group description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 43 mg/m^2 BID, in continuous 28-day cycles.

    Reporting group title
    Pediatric Cohort 58 mg/m^2 BID
    Reporting group description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 58 mg/m^2 BID, in continuous 28-day cycles.

    Reporting group title
    Pediatric Cohort 87 mg/m^2 BID
    Reporting group description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 87 mg/m^2 BID, in continuous 28-day cycles.

    Reporting group values
    Capsule Cohort 1 Capsule Cohort 2 Capsule Cohort 3 Capsule Cohort 4 Capsule Cohort 5a Capsule Cohort 5b Suspension Cohort 6a Suspension Cohort 6b Suspension Cohort 7a Suspension Cohort 7b Pediatric Cohort 43 mg/m^2 BID Pediatric Cohort 58 mg/m^2 BID Pediatric Cohort 87 mg/m^2 BID Total
    Number of subjects
    5 2 2 8 23 3 3 4 14 6 6 4 1 81
    Age Categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: years
        median (full range (min-max))
    55.0 (47 to 64) 53.0 (48 to 58) 59.5 (48 to 71) 34.5 (13 to 58) 51.0 (18 to 76) 48.0 (14 to 51) 56.0 (53 to 58) 48.0 (29 to 69) 47.0 (17 to 75) 56.5 (38 to 73) 5.5 (1 to 9) 6.0 (5 to 10) 2.0 (2 to 2) -
    Gender Categorical
    Units: Subjects
        Female
    2 1 2 7 9 2 1 1 7 2 2 2 0 38
        Male
    3 1 0 1 14 1 2 3 7 4 4 2 1 43

    End points

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    End points reporting groups
    Reporting group title
    Capsule Cohort 1
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 100 mg twice daily (BID), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 2
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 150 mg twice daily (BID), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 3
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 100 mg once daily (QD), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 4
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg once daily (QD), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 5a
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg QD with escalation every 14 days to 75 mg BID, in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 5b
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg QD with escalation every 14 days to 150 mg QD, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort 6a
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50mg BID, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort 6b
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 75mg BID, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort 7a
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50mg QD with escalation after 7 days to 50mg BID, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort 7b
    Reporting group description
    Subjects aged ≥12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50mg QD for 7 days, then 50mg BID for 7 days, then 75mg BID, in continuous 28-day cycles.

    Reporting group title
    Pediatric Cohort 43 mg/m^2 BID
    Reporting group description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 43 mg/m^2 BID, in continuous 28-day cycles.

    Reporting group title
    Pediatric Cohort 58 mg/m^2 BID
    Reporting group description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 58 mg/m^2 BID, in continuous 28-day cycles.

    Reporting group title
    Pediatric Cohort 87 mg/m^2 BID
    Reporting group description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 87 mg/m^2 BID, in continuous 28-day cycles.

    Subject analysis set title
    DLT Analysis Set (subjects aged 12 years and older)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    The DLT Analysis Set (DLT) included all patients enrolled in the dose escalation part who experienced a DLT within the DLT period, and those without a DLT who had completed the safety assessments through the assigned DLT period and had received at least 75% of the planned total dose during Cycle 1.

    Subject analysis set title
    DLT Analysis Set (subjects aged less than 12 years)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    The DLT Analysis Set (DLT) included all patients enrolled in the dose escalation part who experienced a DLT within the DLT period, and those without a DLT who had completed the safety assessments through the assigned DLT period and had received at least 75% of the planned total dose during Cycle 1.

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    All enrolled participants who received 1 or more doses of selitrectinib were included in the Safety Analysis Set

    Subject analysis set title
    Participants with primary CNS tumors
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants with primary CNS tumors evaluated via RANO

    Primary: Maximum tolerated dose (MTD) / recommended dose in patients age 12 years and older and age < 12 years

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    End point title
    Maximum tolerated dose (MTD) / recommended dose in patients age 12 years and older and age < 12 years [1]
    End point description
    The MTD for either age group was defined as the dose level immediately below that in which 2 or more patients experienced a DLT during the assigned DLT period. In table below, w stands for "week", f/b stands for "followed by"
    End point type
    Primary
    End point timeframe
    For patients age 12 years and older: dose-limiting toxicity (DLT) period was up to 42 days; For patients age less than 12 years old: DLT period was 28 days or completion of cycle 1.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis for this endpoint is descriptive.
    End point values
    DLT Analysis Set (subjects aged 12 years and older) DLT Analysis Set (subjects aged less than 12 years)
    Number of subjects analysed
    29 [2]
    7 [3]
    Units: mg QD
        number (not applicable)
    50
    99999
    Notes
    [2] - MTD was either 50mg QD for 1 w, f/b 50mg BID for 1 w, f/b 75mg BID or 50mg BID for 1 w f/b 75mg BID
    [3] - "99999" stands for not determined, as there were no DLTs in this age group.
    No statistical analyses for this end point

    Secondary: Number of participants with TEAE and their severity

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    End point title
    Number of participants with TEAE and their severity
    End point description
    Treatment emergent adverse events (TEAEs) was defined as AEs that start on or after the first administration of study drug. TEAE were collected up to 28 ± 7 days post last dose.
    End point type
    Secondary
    End point timeframe
    From start of the first administration of study drug, up to 28 ± 7 days post last dose
    End point values
    Capsule Cohort 1 Capsule Cohort 2 Capsule Cohort 3 Capsule Cohort 4 Capsule Cohort 5a Capsule Cohort 5b Suspension Cohort 6a Suspension Cohort 6b Suspension Cohort 7a Suspension Cohort 7b Pediatric Cohort 43 mg/m^2 BID Pediatric Cohort 58 mg/m^2 BID Pediatric Cohort 87 mg/m^2 BID
    Number of subjects analysed
    5
    2
    2
    8
    23
    3
    3
    4
    14
    6
    6
    4
    1
    Units: subjects
        Any TEAEs
    5
    2
    2
    8
    23
    3
    3
    4
    14
    6
    6
    4
    1
        Serious TEAEs
    3
    1
    1
    5
    16
    1
    0
    4
    8
    2
    3
    3
    0
        Maximum Severity Grade ≥3
    3
    2
    2
    6
    18
    1
    1
    4
    12
    2
    4
    3
    0
    No statistical analyses for this end point

    Secondary: Number of participants with treatment related TEAE

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    End point title
    Number of participants with treatment related TEAE
    End point description
    The causal relationship between the occurrence of TEAE and study drug was judged by the Investigator, based on the conventions described in protocol
    End point type
    Secondary
    End point timeframe
    Treatment emergent adverse events (TEAEs) was defined as AEs that start on or after the first administration of study drug. TEAE were collected up to 28 ± 7 days post last dose.
    End point values
    Capsule Cohort 1 Capsule Cohort 2 Capsule Cohort 3 Capsule Cohort 4 Capsule Cohort 5a Capsule Cohort 5b Suspension Cohort 6a Suspension Cohort 6b Suspension Cohort 7a Suspension Cohort 7b Pediatric Cohort 43 mg/m^2 BID Pediatric Cohort 58 mg/m^2 BID Pediatric Cohort 87 mg/m^2 BID
    Number of subjects analysed
    5
    2
    2
    8
    23
    3
    3
    4
    14
    6
    6
    4
    1
    Units: subjects
        Any TEAEs
    5
    2
    2
    8
    18
    3
    2
    4
    13
    6
    5
    4
    1
        Serious TEAEs
    0
    0
    0
    0
    0
    0
    0
    2
    1
    0
    1
    1
    0
        Maximum Severity Grade ≥3
    0
    2
    1
    1
    5
    1
    1
    2
    6
    0
    2
    2
    0
    No statistical analyses for this end point

    Secondary: Number of participants with hematology shifts from normal baseline value

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    End point title
    Number of participants with hematology shifts from normal baseline value
    End point description
    Directional shifts from baseline according to normal range are summarized for hematology parameters for the Safety Analysis Set. LLN: lower limit of normal; ULN = upper limit of normal
    End point type
    Secondary
    End point timeframe
    Up to 56 months
    End point values
    Safety Analysis Set
    Number of subjects analysed
    81 [4]
    Units: subjects
        Basophils Count below LLN
    0
        Basophils Count Above ULN
    3
        Eosinophils Count Below LLN
    7
        Eosinophils Count Above ULN
    7
        Monocytes Count Below LLN
    9
        Monocytes Count Above ULN
    7
        Hematocrit Below LLN
    19
        Hematocrit Above ULN
    3
        Red Blood Cell Count Below LLN
    10
        Red Blood Cell Count Above ULN
    8
    Notes
    [4] - Only subjects with baseline assessment and at least one post-baseline assessment were included
    No statistical analyses for this end point

    Secondary: Number participants with chemistry shifts from baseline according to normal range

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    End point title
    Number participants with chemistry shifts from baseline according to normal range
    End point description
    Directional shifts from baseline according to normal range are summarized for chemistry parameters for the Safety Analysis Set. A baseline measurement and at least 1 laboratory or other safety-related measurement obtained after at least 1 dose of study drug was required for inclusion in the analysis of a specific parameter.
    End point type
    Secondary
    End point timeframe
    up to 56 months
    End point values
    Safety Analysis Set
    Number of subjects analysed
    81
    Units: subjects
        Blood Urea Nitrogen Below LLN
    3
        Blood Urea Nitrogen Above ULN
    18
        Lactate Dehydrogenase Below LLN
    3
        Lactate Dehydrogenase Above ULN
    25
        Total Protein Below LLN
    17
        Total Protein Above ULN
    5
        Chloride Below LLN
    9
        Chloride Above ULN
    34
        Calcium Below LLN
    19
        Calcium Above ULN
    9
    No statistical analyses for this end point

    Secondary: Objective Response Rate as determined by the Investigator in participants with a documented NTRK fusion cancer previously treated with a TRK inhibitor

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    End point title
    Objective Response Rate as determined by the Investigator in participants with a documented NTRK fusion cancer previously treated with a TRK inhibitor
    End point description
    Objective Response Rate (ORR) was defined as the proportion of patients with a BOR of confirmed CR, or PR. Response was confirmed by a repeat assessment no less than 28 days later.
    End point type
    Secondary
    End point timeframe
    up to 56 months
    End point values
    Capsule Cohort 1 Capsule Cohort 2 Capsule Cohort 3 Capsule Cohort 4 Capsule Cohort 5a Capsule Cohort 5b Suspension Cohort 6a Suspension Cohort 6b Suspension Cohort 7a Suspension Cohort 7b Pediatric Cohort 43 mg/m^2 BID Pediatric Cohort 58 mg/m^2 BID Pediatric Cohort 87 mg/m^2 BID
    Number of subjects analysed
    5
    2
    2
    8
    23
    3
    3
    4
    14
    6
    6
    4
    1
    Units: Percent (%)
        number (confidence interval 95%)
    20 (0.5 to 71.6)
    0 (0.0 to 84.2)
    50 (1.3 to 98.7)
    37.5 (8.5 to 75.5)
    13.0 (2.8 to 33.6)
    33.3 (0.8 to 90.6)
    33.3 (0.8 to 90.6)
    0 (0.0 to 60.2)
    14.3 (1.8 to 42.8)
    50.0 (11.8 to 88.2)
    33.3 (4.3 to 77.7)
    25.0 (0.6 to 80.6)
    0 (0.0 to 97.5)
    No statistical analyses for this end point

    Secondary: Objective Response Rate as determined by investigator in participants with primary CNS malignancies

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    End point title
    Objective Response Rate as determined by investigator in participants with primary CNS malignancies
    End point description
    primary CNS tumors were evaluated via Response Assessment in Neuro-Oncology (RANO)
    End point type
    Secondary
    End point timeframe
    Objective Response Rate (%) is defined as the proportion of patients with Best Overall Response of confirmed CR, or PR. Response was confirmed by a repeat assessment no less than 28 days.
    End point values
    Participants with primary CNS tumors
    Number of subjects analysed
    14
    Units: percent (%)
        number (confidence interval 95%)
    28.6 (8.4 to 58.1)
    No statistical analyses for this end point

    Secondary: Maximum concentration (Cmax) of BAY2731954 in plasma for BID dosing, Cycle 1 Day 1

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    End point title
    Maximum concentration (Cmax) of BAY2731954 in plasma for BID dosing, Cycle 1 Day 1 [5]
    End point description
    "99999" in data entry fields stands for "Not Calculated"
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1
    Notes
    [5] - 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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 1 Capsule Cohort 2 Suspension Cohort 6a Suspension Cohort 6b Pediatric Cohort 43 mg/m^2 BID Pediatric Cohort 58 mg/m^2 BID Pediatric Cohort 87 mg/m^2 BID
    Number of subjects analysed
    5
    2
    3
    4
    6
    4
    1 [6]
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    182 ± 60.9
    69.1 ± 87.8
    145 ± 13.5
    206 ± 74.0
    228 ± 80.2
    167 ± 72.9
    181 ± 99999
    Notes
    [6] - "99999" in data entry fields stands for "Not Calculated"
    No statistical analyses for this end point

    Secondary: Maximum concentration (Cmax) of BAY2731954 in plasma for BID dosing, Cycle 1 Day 8

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    End point title
    Maximum concentration (Cmax) of BAY2731954 in plasma for BID dosing, Cycle 1 Day 8 [7]
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 8
    Notes
    [7] - 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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 1 Suspension Cohort 7a Suspension Cohort 7b Pediatric Cohort 43 mg/m^2 BID Pediatric Cohort 58 mg/m^2 BID
    Number of subjects analysed
    5
    10
    6
    6
    2
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    150 ± 62.1
    161 ± 58.3
    136 ± 57.8
    274 ± 41.8
    229 ± 37.6
    No statistical analyses for this end point

    Secondary: Maximum concentration (Cmax) of BAY2731954 in plasma for BID dosing, Cycle 1 Day 15

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    End point title
    Maximum concentration (Cmax) of BAY2731954 in plasma for BID dosing, Cycle 1 Day 15 [8]
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 15
    Notes
    [8] - 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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 5a Capsule Cohort 5b Suspension Cohort 6a Suspension Cohort 6b Suspension Cohort 7b Pediatric Cohort 58 mg/m^2 BID
    Number of subjects analysed
    14
    3
    2
    3
    5
    2
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    159 ± 93.3
    244 ± 46.7
    119 ± 3.6
    101 ± 41.6
    198 ± 48.1
    354 ± 41.6
    No statistical analyses for this end point

    Secondary: Area under the concentration versus time curve of BAY2731954 in plasma for BID dosing, Cycle 1 Day 1

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    End point title
    Area under the concentration versus time curve of BAY2731954 in plasma for BID dosing, Cycle 1 Day 1 [9]
    End point description
    "99999" in data entry fields stands for "Not Calculated"
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1
    Notes
    [9] - 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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 1 Capsule Cohort 2 Suspension Cohort 6a Suspension Cohort 6b Pediatric Cohort 43 mg/m^2 BID Pediatric Cohort 58 mg/m^2 BID Pediatric Cohort 87 mg/m^2 BID
    Number of subjects analysed
    5
    1 [10]
    3
    4
    6
    2
    1 [11]
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        AUC(0-10)
    527 ± 85.0
    525 ± 99999
    380 ± 15.3
    459 ± 57.2
    492 ± 60.5
    243 ± 57.5
    229 ± 99999
        AUC(0-12)
    537 ± 87.3
    538 ± 99999
    384 ± 15.6
    464 ± 57.0
    493 ± 60.5
    243 ± 57.5
    229 ± 99999
    Notes
    [10] - "99999" in data entry fields stands for "Not Calculated"
    [11] - "99999" in data entry fields stands for "Not Calculated"
    No statistical analyses for this end point

    Secondary: Area under the concentration versus time curve of BAY2731954 in plasma for BID dosing, Cycle 1 Day 8

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    End point title
    Area under the concentration versus time curve of BAY2731954 in plasma for BID dosing, Cycle 1 Day 8 [12]
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 8
    Notes
    [12] - 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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 1 Capsule Cohort 5a Suspension Cohort 7a Suspension Cohort 7b
    Number of subjects analysed
    5
    19
    10
    6
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        AUC(0-10)
    593 ± 120.4
    459 ± 101.4
    401 ± 48.2
    389 ± 51.1
        AUC(0-12)
    638 ± 135.6
    500 ± 100.7
    406 ± 48.5
    394 ± 51.6
    No statistical analyses for this end point

    Secondary: Area under the concentration versus time curve of BAY2731954 in plasma for BID dosing, Cycle 1 Day 15

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    End point title
    Area under the concentration versus time curve of BAY2731954 in plasma for BID dosing, Cycle 1 Day 15 [13]
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 15
    Notes
    [13] - 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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 5a Suspension Cohort 6a Suspension Cohort 6b Suspension Cohort 7b Pediatric Cohort 58 mg/m^2 BID
    Number of subjects analysed
    14
    2
    3
    5
    2
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        AUC(0-10)
    454 ± 89.7
    320 ± 4.1
    287 ± 49.5
    558 ± 57.4
    436 ± 171
        AUC(0-12)
    470 ± 91.4
    338 ± 3.0
    295 ± 50.3
    575 ± 60.5
    449 ± 177.8
    No statistical analyses for this end point

    Secondary: Area under the concentration versus time curve AUC(0-24) of BAY2731954 in plasma for QD dosing, Cycle 1 Day 1

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    End point title
    Area under the concentration versus time curve AUC(0-24) of BAY2731954 in plasma for QD dosing, Cycle 1 Day 1 [14]
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1
    Notes
    [14] - 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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 3 Capsule Cohort 4 Capsule Cohort 5a Capsule Cohort 5b Suspension Cohort 7a Suspension Cohort 7b
    Number of subjects analysed
    2
    6
    20
    2
    9
    6
    Units: h*ng/mL
        geometric mean (geometric coefficient of variation)
    470 ± 37.3
    435 ± 173.5
    385 ± 105.7
    197 ± 27.6
    318 ± 39.7
    366 ± 42.3
    No statistical analyses for this end point

    Secondary: Area under the concentration versus time curve AUC(0-24) of BAY2731954 in plasma for QD dosing, Cycle 1 Day 8

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    End point title
    Area under the concentration versus time curve AUC(0-24) of BAY2731954 in plasma for QD dosing, Cycle 1 Day 8 [15]
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 8
    Notes
    [15] - 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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 3 Capsule Cohort 4 Capsule Cohort 5a Capsule Cohort 5b
    Number of subjects analysed
    1 [16]
    7
    19
    3
    Units: h*ng/mL
        geometric mean (geometric coefficient of variation)
    543 ± 99999
    801 ± 98.9
    618 ± 99.5
    514 ± 101.6
    Notes
    [16] - "99999" in data entry fields stands for "Not Calculated"
    No statistical analyses for this end point

    Secondary: Area under the concentration versus time curve AUC(0-24) of BAY2731954 in plasma for QD dosing, Cycle 1 Day 15

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    End point title
    Area under the concentration versus time curve AUC(0-24) of BAY2731954 in plasma for QD dosing, Cycle 1 Day 15 [17]
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 15
    Notes
    [17] - 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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 5b
    Number of subjects analysed
    3
    Units: h*ng/mL
        geometric mean (geometric coefficient of variation)
    907 ± 50.7
    No statistical analyses for this end point

    Secondary: Maximum concentration (Cmax) of BAY2731954 in plasma for BID dosing, Cycle 2 Day 1

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    End point title
    Maximum concentration (Cmax) of BAY2731954 in plasma for BID dosing, Cycle 2 Day 1 [18]
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 2 Day 1
    Notes
    [18] - 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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 5a
    Number of subjects analysed
    13
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    169 ± 135.4
    No statistical analyses for this end point

    Secondary: Area under the concentration versus time curve of BAY2731954 in plasma for BID dosing, Cycle 2 Day 1

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    End point title
    Area under the concentration versus time curve of BAY2731954 in plasma for BID dosing, Cycle 2 Day 1 [19]
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 2 Day 1
    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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 5a
    Number of subjects analysed
    13
    Units: h*ng/mL
    geometric mean (geometric coefficient of variation)
        AUC(0-10)
    504 ± 123.5
        AUC(0-12)
    520 ± 124.5
    No statistical analyses for this end point

    Secondary: Area under the concentration versus time curve AUC(0-24) of BAY2731954 in plasma for QD dosing, Cycle 2 Day 1

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    End point title
    Area under the concentration versus time curve AUC(0-24) of BAY2731954 in plasma for QD dosing, Cycle 2 Day 1 [20]
    End point description
    End point type
    Secondary
    End point timeframe
    Cycle 2 Day 1
    Notes
    [20] - 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: This endpoint is only reporting PK data of arms with certain dosage schedule on certain day.
    End point values
    Capsule Cohort 5b
    Number of subjects analysed
    2
    Units: h*ng/mL
        geometric mean (geometric coefficient of variation)
    761 ± 59.0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    TEAEs was defined as AEs that start on or after the first administration of study drug, TEAEs were collected up to 28 +/- 7 days post last dose.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Capsule Cohort 2
    Reporting group description
    Subjects aged >= 12 years in this group were administrated with selitrectinib (BAY2731954) capsule 150 mg twice daily (BID), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 1
    Reporting group description
    Subjects aged >= 12 years in this group were administrated with selitrectinib (BAY2731954) capsule 100 mg twice daily (BID), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 3
    Reporting group description
    Subjects aged >= 12 years in this group were administrated with selitrectinib (BAY2731954) capsule 100 mg once daily (QD), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 4
    Reporting group description
    Subjects aged >= 12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg once daily (QD), in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 5a
    Reporting group description
    Subjects aged >= 12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg QD with escalation every 14 days to 75 mg BID, in continuous 28-day cycles.

    Reporting group title
    Capsule Cohort 5b
    Reporting group description
    Subjects aged >= 12 years in this group were administrated with selitrectinib (BAY2731954) capsule 50 mg QD with escalation every 14 days to 150 mg QD, in continuous 28-day cycles.

    Reporting group title
    Pediatric Cohort 87 mg/mm^2 BID
    Reporting group description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 87 mg/m^2 BID, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort 6b
    Reporting group description
    Subjects aged >= 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 75mg BID, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort 7b
    Reporting group description
    Subjects aged >= 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50 mg BID for 7 days, then 75 mg BID for 7 days, then 100 mg BID, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort7a
    Reporting group description
    Subjects aged >= 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50 mg BID with escalation after 7 days to 75 mg BID, in continuous 28-day cycles.

    Reporting group title
    Pediatric Cohort 58 mg/mm^2 BID
    Reporting group description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 58 mg/m^2 BID, in continuous 28-day cycles.

    Reporting group title
    Pediatric Cohort 43 mg/mm^2 BID
    Reporting group description
    Subjects aged < 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 43 mg/m^2 BID, in continuous 28-day cycles.

    Reporting group title
    Suspension Cohort 6a
    Reporting group description
    Subjects aged >= 12 years in this group were administrated with selitrectinib (BAY2731954) liquid suspension 50mg BID, in continuous 28-day cycles.

    Serious adverse events
    Capsule Cohort 2 Capsule Cohort 1 Capsule Cohort 3 Capsule Cohort 4 Capsule Cohort 5a Capsule Cohort 5b Pediatric Cohort 87 mg/mm^2 BID Suspension Cohort 6b Suspension Cohort 7b Suspension Cohort7a Pediatric Cohort 58 mg/mm^2 BID Pediatric Cohort 43 mg/mm^2 BID Suspension Cohort 6a
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 2 (50.00%)
    3 / 5 (60.00%)
    1 / 2 (50.00%)
    5 / 8 (62.50%)
    16 / 23 (69.57%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    4 / 4 (100.00%)
    2 / 6 (33.33%)
    8 / 14 (57.14%)
    3 / 4 (75.00%)
    3 / 6 (50.00%)
    0 / 3 (0.00%)
         number of deaths (all causes)
    2
    4
    1
    7
    18
    3
    0
    2
    3
    9
    2
    4
    2
         number of deaths resulting from adverse events
    1
    2
    0
    4
    7
    0
    0
    2
    0
    3
    1
    2
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Glioblastoma
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stromal tumour
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine carcinoma
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal squamous cell carcinoma
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 2 (50.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cyst
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 5 (20.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    3 / 23 (13.04%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    2 / 23 (8.70%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    2 / 23 (8.70%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood glucose increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tracheal obstruction
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Facial paralysis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Coma
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Facial paresis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    2 / 23 (8.70%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    2 / 23 (8.70%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary obstruction
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 3
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary tract infection
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypernatraemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Capsule Cohort 2 Capsule Cohort 1 Capsule Cohort 3 Capsule Cohort 4 Capsule Cohort 5a Capsule Cohort 5b Pediatric Cohort 87 mg/mm^2 BID Suspension Cohort 6b Suspension Cohort 7b Suspension Cohort7a Pediatric Cohort 58 mg/mm^2 BID Pediatric Cohort 43 mg/mm^2 BID Suspension Cohort 6a
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 2 (100.00%)
    5 / 5 (100.00%)
    2 / 2 (100.00%)
    8 / 8 (100.00%)
    22 / 23 (95.65%)
    3 / 3 (100.00%)
    1 / 1 (100.00%)
    4 / 4 (100.00%)
    6 / 6 (100.00%)
    14 / 14 (100.00%)
    4 / 4 (100.00%)
    6 / 6 (100.00%)
    3 / 3 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to meninges
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Tumour pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Skin papilloma
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Cancer pain
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Tumour exudation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Vascular disorders
    Lymphoedema
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Hypotension
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    2 / 23 (8.70%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    1
    2
    0
    0
    2
    0
    1
    0
    1
    0
    Hypertension
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    2
    0
    2
    0
    Haematoma
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Embolism venous
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Flushing
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    2
    0
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    3 / 23 (13.04%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    5
    0
    1
    0
    0
    0
    1
    0
    0
    Chest discomfort
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Chest pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    1
    0
    Chills
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 2 (50.00%)
    1 / 8 (12.50%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    3
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Drug withdrawal syndrome
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    2 / 23 (8.70%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 2 (50.00%)
    1 / 5 (20.00%)
    1 / 2 (50.00%)
    2 / 8 (25.00%)
    5 / 23 (21.74%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    3 / 14 (21.43%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
    1 / 3 (33.33%)
         occurrences all number
    2
    1
    2
    4
    6
    0
    0
    0
    2
    3
    1
    2
    1
    Gait disturbance
         subjects affected / exposed
    0 / 2 (0.00%)
    2 / 5 (40.00%)
    0 / 2 (0.00%)
    3 / 8 (37.50%)
    6 / 23 (26.09%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    3 / 14 (21.43%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    3
    9
    2
    0
    0
    4
    4
    0
    0
    0
    Oedema
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Malaise
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 2 (50.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    2
    0
    1
    0
    0
    0
    0
    1
    0
    1
    0
    Face oedema
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Energy increased
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    Localised oedema
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    3 / 23 (13.04%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    4 / 4 (100.00%)
    2 / 6 (33.33%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    1
    5
    0
    0
    5
    2
    1
    0
    1
    0
    Pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    3 / 8 (37.50%)
    2 / 23 (8.70%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    3 / 4 (75.00%)
    0 / 6 (0.00%)
    3 / 14 (21.43%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    3
    2
    0
    0
    3
    0
    3
    2
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    1 / 2 (50.00%)
    2 / 8 (25.00%)
    2 / 23 (8.70%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
    1 / 4 (25.00%)
    3 / 6 (50.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    7
    4
    0
    0
    0
    1
    1
    4
    6
    0
    Swelling
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Thirst
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Reproductive system and breast disorders
    Breast pain
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dysmenorrhoea
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Pelvic pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Scrotal oedema
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Scrotal pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Penile oedema
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    5 / 23 (21.74%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    2 / 4 (50.00%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    0
    1
    7
    0
    0
    0
    0
    1
    5
    1
    1
    Bronchospasm
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    8 / 23 (34.78%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    4 / 4 (100.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    1
    13
    0
    0
    4
    1
    0
    0
    0
    0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Hypercapnia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    1 / 1 (100.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Pneumothorax
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    Hypoxia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    2 / 23 (8.70%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    0
    0
    1
    0
    1
    0
    Haemoptysis
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Pleural effusion
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 2 (50.00%)
    1 / 8 (12.50%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    3 / 6 (50.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    0
    0
    0
    0
    0
    3
    0
    Productive cough
         subjects affected / exposed
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    1
    1
    1
    0
    0
    0
    Respiratory failure
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    2
    0
    0
    Sneezing
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Lower respiratory tract inflammation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Paranasal sinus discomfort
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    1 / 3 (33.33%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    2 / 4 (50.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    2
    3
    0
    Wheezing
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    1
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Delirium
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Confusional state
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    3 / 23 (13.04%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    1
    0
    0
    0
    0
    0
    Anxiety
         subjects affected / exposed
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    2 / 23 (8.70%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    1
    4
    0
    0
    0
    0
    1
    0
    0
    0
    Disorientation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Derealisation
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Hallucination, auditory
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Hallucination
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    1 / 23 (4.35%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    2 / 14 (14.29%)
    2 / 4 (50.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    2
    2
    0
    0
    Hallucination, visual
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Restlessness
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Sleep disorder
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    1 / 8 (12.50%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Irritability
         subjects affected / exposed
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 2 (0.00%)
    0 / 8 (0.00%)
    0 / 23 (0.00%)
    0 / 3 (0.00%)
    0 / 1 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)