Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   36818   clinical trials with a EudraCT protocol, of which   6079   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous (IV) and Powder for Oral Suspension Formulations of Posaconazole (POS) in Immunocompromised Pediatric Subjects with Neutropenia

    Summary
    EudraCT number
    2014-002807-10
    Trial protocol
    DE   NO   SE   DK   CZ   ES   BE   IT   Outside EU/EEA  
    Global end of trial date
    03 Sep 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    09 Mar 2019
    First version publication date
    09 Mar 2019
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    5592-097
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02452034
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-000468-PIP02-12
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Sep 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Sep 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study aims to evaluate the pharmacokinetics (PK) of posaconazole (POS) administered intravenously (IV) or orally to immunocompromised pediatric participants.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    07 Sep 2015
    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: 13
    Country: Number of subjects enrolled
    Czech Republic: 19
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    Germany: 27
    Country: Number of subjects enrolled
    Guatemala: 4
    Country: Number of subjects enrolled
    Italy: 8
    Country: Number of subjects enrolled
    Norway: 7
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Sweden: 4
    Country: Number of subjects enrolled
    Thailand: 5
    Country: Number of subjects enrolled
    United States: 23
    Worldwide total number of subjects
    118
    EEA total number of subjects
    86
    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)
    0
    Children (2-11 years)
    73
    Adolescents (12-17 years)
    45
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Immunocompromised participants aged 2 to 17 years old, with neutropenia expected to last for at least 7 days following start of study treatment, were enrolled in this study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    3.5 mg/kg POS (2-7 years old)
    Arm description
    Children 2 to less than 7 years of age received posaconazole (POS) at 3.5 mg/kg by intravenous (IV) solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 3.5 mg/kg POS once daily by powder for oral suspension (PFS) for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Posaconazole at 3.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10.

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Powder and solvent for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Posaconazole at 3.5 mg/kg once daily by PFS for a minimum of 10 days

    Arm title
    3.5 mg/kg POS (7-17 years old)
    Arm description
    Children 7 to 17 years of age received POS at 3.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 3.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Posaconazole at 3.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10.

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Powder and solvent for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Posaconazole at 3.5 mg/kg once daily by PFS for a minimum of 10 days

    Arm title
    4.5 mg/kg POS (2-7 years old)
    Arm description
    Children 2 to less than 7 years of age received POS at 4.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 4.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Posaconazole at 4.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10.

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Powder and solvent for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Posaconazole at 4.5 mg/kg once daily by PFS for a minimum of 10 days

    Arm title
    4.5 mg/kg POS (7-17 years old)
    Arm description
    Children 7 to 17 years of age received POS at 4.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 4.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Powder and solvent for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Posaconazole at 4.5 mg/kg once daily by PFS for a minimum of 10 days

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Posaconazole at 4.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10.

    Arm title
    6 mg/kg POS (2-7 years old)
    Arm description
    Children 2 to less than 7 years of age received POS at 6 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 6 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Posaconazole at 6 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10.

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Powder and solvent for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Posaconazole at 6 mg/kg once daily by PFS for a minimum of 10 days

    Arm title
    6 mg/kg POS (7-17 years old)
    Arm description
    Children 7 to 17 years of age received POS at 6 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 6 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.
    Arm type
    Experimental

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Powder and solvent for oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Posaconazole at 6 mg/kg once daily by PFS for a minimum of 10 days

    Investigational medicinal product name
    Posaconazole
    Investigational medicinal product code
    Other name
    Noxafil
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Posaconazole at 6 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10.

    Number of subjects in period 1
    3.5 mg/kg POS (2-7 years old) 3.5 mg/kg POS (7-17 years old) 4.5 mg/kg POS (2-7 years old) 4.5 mg/kg POS (7-17 years old) 6 mg/kg POS (2-7 years old) 6 mg/kg POS (7-17 years old)
    Started
    16
    21
    15
    17
    20
    29
    Treated
    14
    21
    15
    16
    20
    29
    Completed
    14
    20
    14
    16
    19
    26
    Not completed
    2
    1
    1
    1
    1
    3
         Protocol deviation
    -
    -
    -
    -
    -
    1
         Death
    -
    -
    -
    -
    1
    1
         Physician decision
    -
    1
    1
    -
    -
    -
         Adverse event, non-fatal
    -
    -
    -
    -
    -
    1
         Screen Failure
    1
    -
    -
    1
    -
    -
         Withdrawn by Parent/Guardian
    1
    -
    -
    -
    -
    -

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    3.5 mg/kg POS (2-7 years old)
    Reporting group description
    Children 2 to less than 7 years of age received posaconazole (POS) at 3.5 mg/kg by intravenous (IV) solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 3.5 mg/kg POS once daily by powder for oral suspension (PFS) for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    3.5 mg/kg POS (7-17 years old)
    Reporting group description
    Children 7 to 17 years of age received POS at 3.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 3.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    4.5 mg/kg POS (2-7 years old)
    Reporting group description
    Children 2 to less than 7 years of age received POS at 4.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 4.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    4.5 mg/kg POS (7-17 years old)
    Reporting group description
    Children 7 to 17 years of age received POS at 4.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 4.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    6 mg/kg POS (2-7 years old)
    Reporting group description
    Children 2 to less than 7 years of age received POS at 6 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 6 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    6 mg/kg POS (7-17 years old)
    Reporting group description
    Children 7 to 17 years of age received POS at 6 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 6 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group values
    3.5 mg/kg POS (2-7 years old) 3.5 mg/kg POS (7-17 years old) 4.5 mg/kg POS (2-7 years old) 4.5 mg/kg POS (7-17 years old) 6 mg/kg POS (2-7 years old) 6 mg/kg POS (7-17 years old) Total
    Number of subjects
    16 21 15 17 20 29 118
    Age Categorical
    Units: Subjects
        In utero
    0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0 0 0
        Children (2-11 years)
    16 4 15 5 20 13 73
        Adolescents (12-17 years)
    0 17 0 12 0 16 45
        Adults (18-64 years)
    0 0 0 0 0 0 0
        From 65-84 years
    0 0 0 0 0 0 0
        85 years and over
    0 0 0 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    3.9 ± 1.5 13.9 ± 2.1 4.1 ± 1.4 12.5 ± 2.7 3.9 ± 1.6 12.0 ± 3.5 -
    Gender Categorical
    Units: Subjects
        Female
    3 11 8 8 10 10 50
        Male
    13 10 7 9 10 19 68
    Race
    Units: Subjects
        Asian
    4 1 2 2 1 1 11
        Black Or African American
    0 0 0 0 1 2 3
        Multiple
    0 2 0 2 0 0 4
        Native Hawaiian Or Other Pacific Islander
    0 0 1 0 0 0 1
        White
    12 18 12 13 18 26 99
    Ethnicity
    Units: Subjects
        Hispanic Or Latino
    1 2 2 4 1 2 12
        Not Hispanic Or Latino
    15 19 12 12 18 27 103
        Not Reported
    0 0 1 1 0 0 2
        Unknown
    0 0 0 0 1 0 1

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    3.5 mg/kg POS (2-7 years old)
    Reporting group description
    Children 2 to less than 7 years of age received posaconazole (POS) at 3.5 mg/kg by intravenous (IV) solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 3.5 mg/kg POS once daily by powder for oral suspension (PFS) for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    3.5 mg/kg POS (7-17 years old)
    Reporting group description
    Children 7 to 17 years of age received POS at 3.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 3.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    4.5 mg/kg POS (2-7 years old)
    Reporting group description
    Children 2 to less than 7 years of age received POS at 4.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 4.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    4.5 mg/kg POS (7-17 years old)
    Reporting group description
    Children 7 to 17 years of age received POS at 4.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 4.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    6 mg/kg POS (2-7 years old)
    Reporting group description
    Children 2 to less than 7 years of age received POS at 6 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 6 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    6 mg/kg POS (7-17 years old)
    Reporting group description
    Children 7 to 17 years of age received POS at 6 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 6 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Primary: Area under the plasma concentration versus time curve (AUC) from time 0 to 24 hours post-dose for POS

    Close Top of page
    End point title
    Area under the plasma concentration versus time curve (AUC) from time 0 to 24 hours post-dose for POS [1]
    End point description
    Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma AUC from time 0-24 hours post-dose (AUC0- 24hr) of posaconazole. A non-compartmental analysis of posaconazole plasma concentrations was performed. Results are reported for each treatment arm according to the formulation that participants received (IV or PFS). Participants receiving both formulations were counted once for each formulation. The population analyzed was all treated participants who received at least 7 days of POS dosing (IV and PFS), completed the full POS PK sampling, and met pre-specified acceptability criteria.
    End point type
    Primary
    End point timeframe
    Any day from Day 7 to Day 10 of therapy for each formulation (up to 28 days) at pre-dose, within 15 minutes after end of infusion (up to 2 hours), and 4, 6, 8, 12, 24 hours post-infusion
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint.
    End point values
    3.5 mg/kg POS (2-7 years old) 3.5 mg/kg POS (7-17 years old) 4.5 mg/kg POS (2-7 years old) 4.5 mg/kg POS (7-17 years old) 6 mg/kg POS (2-7 years old) 6 mg/kg POS (7-17 years old)
    Number of subjects analysed
    11 [2]
    19 [3]
    14 [4]
    15 [5]
    17 [6]
    24 [7]
    Units: hr*ng/mL
    geometric mean (geometric coefficient of variation)
        IV
    17800 ± 55.0
    27300 ± 49.7
    25600 ± 30.0
    29800 ± 42.9
    31100 ± 48.9
    44200 ± 41.5
        PFS
    12200 ± 36.0
    20700 ± 33.8
    21600 ± 64.5
    28700 ± 33.7
    23000 ± 47.3
    25000 ± 184.3
    Notes
    [2] - IV n= 11; PFS n= 5
    [3] - IV n= 19; PFS n= 10
    [4] - IV n= 14; PFS n= 8
    [5] - IV n= 15; PFS n= 8
    [6] - IV n= 17; PFS n= 7
    [7] - IV n= 24; PFS n= 12
    No statistical analyses for this end point

    Primary: Maximum plasma concentration (Cmax) for POS

    Close Top of page
    End point title
    Maximum plasma concentration (Cmax) for POS [8]
    End point description
    Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma Cmax of posaconazole. A noncompartmental analysis of posaconazole plasma concentrations was performed. Results are reported for each treatment arm according to the formulation that participants received (IV or PFS). Participants receiving both formulations were counted once for each formulation. The population analyzed was all treated participants who received at least 7 days of POS dosing (IV and PFS), completed the full POS PK sampling, and met pre-specified acceptability criteria.
    End point type
    Primary
    End point timeframe
    Any day from Day 7 to Day 10 of therapy for each formulation (up to 28 days) at pre-dose, within 15 minutes after end of infusion (up to 2 hours), and 4, 6, 8, 12, 24 hours post-infusion
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint.
    End point values
    3.5 mg/kg POS (2-7 years old) 3.5 mg/kg POS (7-17 years old) 4.5 mg/kg POS (2-7 years old) 4.5 mg/kg POS (7-17 years old) 6 mg/kg POS (2-7 years old) 6 mg/kg POS (7-17 years old)
    Number of subjects analysed
    11 [9]
    19 [10]
    14 [11]
    15 [12]
    17 [13]
    24 [14]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        IV
    1590 ± 43.1
    2450 ± 72.7
    2320 ± 39.8
    2310 ± 40.3
    3060 ± 54.1
    3340 ± 39.4
        PFS
    884 ± 44.4
    1340 ± 30.8
    1550 ± 40.8
    1670 ± 28.5
    1510 ± 43.4
    1370 ± 178.5
    Notes
    [9] - IV n=11; PFS n=5
    [10] - IV n=19; PFS n=10
    [11] - IV n=14; PFS n=8
    [12] - IV n=15; PFS n=8
    [13] - IV n=17; PFS n=7
    [14] - IV n=24; PFS n=12
    No statistical analyses for this end point

    Primary: Minimum plasma concentration (Cmin) for POS

    Close Top of page
    End point title
    Minimum plasma concentration (Cmin) for POS [15]
    End point description
    Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma Cmin of posaconazole. A non-compartmental analysis of posaconazole plasma concentrations was performed. Results are reported for each treatment arm according to the formulation that participants received (IV or PFS). Participants receiving both formulations were counted once for each formulation. The population analyzed was all treated participants who received at least 7 days of POS dosing (IV and PFS), completed the full POS PK sampling, and met pre-specified acceptability criteria.
    End point type
    Primary
    End point timeframe
    Any day from Day 7 to Day 10 of therapy for each formulation (up to 28 days) at pre-dose, within 15 minutes after end of infusion (up to 2 hours), and 4, 6, 8, 12, 24 hours post-infusion
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint.
    End point values
    3.5 mg/kg POS (2-7 years old) 3.5 mg/kg POS (7-17 years old) 4.5 mg/kg POS (2-7 years old) 4.5 mg/kg POS (7-17 years old) 6 mg/kg POS (2-7 years old) 6 mg/kg POS (7-17 years old)
    Number of subjects analysed
    11 [16]
    19 [17]
    14 [18]
    15 [19]
    17 [20]
    24 [21]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        IV
    400 ± 81.3
    670 ± 65.1
    501 ± 56.8
    737 ± 66.0
    626 ± 104.8
    1160 ± 60.4
        PFS
    254 ± 45.6
    579 ± 44.9
    476 ± 164.6
    790 ± 48.2
    542 ± 68.8
    713 ± 300.6
    Notes
    [16] - IV n=11; PFS n=5
    [17] - IV n=19; PFS n=10
    [18] - IV n=14; PFS n=8
    [19] - IV n=15; PFS n=8
    [20] - IV n=17; PFS n=7
    [21] - IV n=24; PFS n=12
    No statistical analyses for this end point

    Primary: Average steady-state plasma concentration (Cavg) for POS

    Close Top of page
    End point title
    Average steady-state plasma concentration (Cavg) for POS [22]
    End point description
    Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma Cavg of posaconazole. A non-compartmental analysis of posaconazole plasma concentrations was performed. Results are reported for each treatment arm according to the formulation that participants received (IV or PFS). Participants receiving both formulations were counted once for each formulation. The population analyzed was all treated participants who received at least 7 days of POS dosing (IV and PFS), completed the full POS PK sampling, and met pre-specified acceptability criteria.
    End point type
    Primary
    End point timeframe
    Any day from Day 7 to Day 10 of therapy for each formulation (up to 28 days) at pre-dose, within 15 minutes after end of infusion (up to 2 hours), and 4, 6, 8, 12, 24 hours post-infusion
    Notes
    [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint.
    End point values
    3.5 mg/kg POS (2-7 years old) 3.5 mg/kg POS (7-17 years old) 4.5 mg/kg POS (2-7 years old) 4.5 mg/kg POS (7-17 years old) 6 mg/kg POS (2-7 years old) 6 mg/kg POS (7-17 years old)
    Number of subjects analysed
    11 [23]
    19 [24]
    14 [25]
    15 [26]
    17 [27]
    24 [28]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        IV
    743 ± 55.0
    1140 ± 49.7
    1070 ± 30.0
    1240 ± 42.9
    1300 ± 48.9
    1840 ± 41.5
        PFS
    510 ± 36.0
    861 ± 33.8
    901 ± 64.5
    1200 ± 33.7
    960 ± 47.3
    1040 ± 184.3
    Notes
    [23] - IV n=11; PFS n=5
    [24] - IV n=19; PFS n=10
    [25] - IV n=14; PFS n=8
    [26] - IV n=15; PFS n=8
    [27] - IV n=17; PFS n=7
    [28] - IV n=24; PFS n=12
    No statistical analyses for this end point

    Primary: Time of maximum plasma concentration (Tmax) for POS

    Close Top of page
    End point title
    Time of maximum plasma concentration (Tmax) for POS [29]
    End point description
    Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma Tmax of posaconazole. A non-compartmental analysis of posaconazole plasma concentrations was performed. Results are reported for each treatment arm according to the formulation that participants received (IV or PFS). Participants receiving both formulations were counted once for each formulation. The population analyzed was all treated participants who received at least 7 days of POS dosing (IV and PFS), completed the full POS PK sampling, and met pre-specified acceptability criteria.
    End point type
    Primary
    End point timeframe
    Any day from Day 7 to Day 10 of therapy for each formulation (up to 28 days) at pre-dose, within 15 minutes after end of infusion (up to 2 hours), and 4, 6, 8, 12, 24 hours post-infusion
    Notes
    [29] - 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: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint.
    End point values
    3.5 mg/kg POS (2-7 years old) 3.5 mg/kg POS (7-17 years old) 4.5 mg/kg POS (2-7 years old) 4.5 mg/kg POS (7-17 years old) 6 mg/kg POS (2-7 years old) 6 mg/kg POS (7-17 years old)
    Number of subjects analysed
    11 [30]
    19 [31]
    14 [32]
    15 [33]
    17 [34]
    24 [35]
    Units: Hours
    median (full range (min-max))
        IV
    1.78 (1.67 to 5.53)
    1.77 (0.00 to 3.50)
    1.78 (1.42 to 5.90)
    1.75 (1.52 to 1.80)
    1.75 (1.57 to 1.83)
    1.77 (1.33 to 6.00)
        PFS
    3.83 (1.92 to 4.25)
    2.20 (1.92 to 6.03)
    3.82 (1.88 to 5.92)
    6.14 (1.98 to 7.98)
    4.00 (2.17 to 7.92)
    2.78 (0.00 to 4.00)
    Notes
    [30] - IV n=11; PFS n=5
    [31] - IV n=19; PFS n=10
    [32] - IV n=14; PFS n=8
    [33] - IV n=15; PFS n=8
    [34] - IV n=17; PFS n=7
    [35] - IV n=24; PFS n=12
    No statistical analyses for this end point

    Primary: Total body clearance (CL) for POS administered by IV

    Close Top of page
    End point title
    Total body clearance (CL) for POS administered by IV [36]
    End point description
    Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma CL of posaconazole administered by IV. A non-compartmental analysis of posaconazole plasma concentrations was performed. Results are reported for participants that received IV treatment. The population analyzed was all treated participants who received at least 7 days of POS IV solution therapy, completed the full POS PK sampling while on POS IV solution, and met pre-specified acceptability criteria.
    End point type
    Primary
    End point timeframe
    Any day from Day 7 to Day 10 of therapy at pre-dose, within 15 minutes after end of infusion (up to 2 hours), and 4, 6, 8, 12, 24 hours post-infusion
    Notes
    [36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint.
    End point values
    3.5 mg/kg POS (2-7 years old) 3.5 mg/kg POS (7-17 years old) 4.5 mg/kg POS (2-7 years old) 4.5 mg/kg POS (7-17 years old) 6 mg/kg POS (2-7 years old) 6 mg/kg POS (7-17 years old)
    Number of subjects analysed
    11
    19
    14
    15
    17
    24
    Units: L/hr
        geometric mean (geometric coefficient of variation)
    3.39 ± 52.8
    6.64 ± 38.6
    2.97 ± 36.2
    6.69 ± 37.3
    3.27 ± 49.3
    4.76 ± 55.7
    No statistical analyses for this end point

    Primary: Apparent total body clearance (CL/F) for POS administered by PFS

    Close Top of page
    End point title
    Apparent total body clearance (CL/F) for POS administered by PFS [37]
    End point description
    Blood was collected from pre-dose up to 24 hours post-dose in order to determine the plasma CL/F of posaconazole administered by PFS. A non-compartmental analysis of posaconazole plasma concentrations was performed. Results are reported for participants that received PFS treatment. The population analyzed was all treated participants who received at least 7 days of POS PFS therapy, completed the full POS PK sampling while on POS PFS, and met pre-specified acceptability criteria.
    End point type
    Primary
    End point timeframe
    Any day from Day 7 to Day 10 of therapy (up to 28 days) at pre-dose, within 15 minutes after end of infusion (up to 2 hours), and 4, 6, 8, 12, 24 hours post-infusion
    Notes
    [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint.
    End point values
    3.5 mg/kg POS (2-7 years old) 3.5 mg/kg POS (7-17 years old) 4.5 mg/kg POS (2-7 years old) 4.5 mg/kg POS (7-17 years old) 6 mg/kg POS (2-7 years old) 6 mg/kg POS (7-17 years old)
    Number of subjects analysed
    5
    10
    8
    8
    7
    12
    Units: L/hr
        geometric mean (geometric coefficient of variation)
    4.97 ± 29.1
    7.67 ± 39.9
    3.49 ± 59.1
    7.84 ± 49.4
    4.60 ± 35.2
    8.39 ± 190.3
    No statistical analyses for this end point

    Secondary: Number of participants with an Adverse Event (AE)

    Close Top of page
    End point title
    Number of participants with an Adverse Event (AE)
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an AE. The population analyzed was all participants who received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    14 days after end of treatment (Up to 42 days)
    End point values
    3.5 mg/kg POS (2-7 years old) 3.5 mg/kg POS (7-17 years old) 4.5 mg/kg POS (2-7 years old) 4.5 mg/kg POS (7-17 years old) 6 mg/kg POS (2-7 years old) 6 mg/kg POS (7-17 years old)
    Number of subjects analysed
    14
    21
    15
    16
    20
    29
    Units: Participants
    13
    21
    15
    16
    19
    29
    No statistical analyses for this end point

    Secondary: Number of participants who discontinued treatment of study drug due to an Adverse Event (AE)

    Close Top of page
    End point title
    Number of participants who discontinued treatment of study drug due to an Adverse Event (AE)
    End point description
    An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an AE. The population analyzed was all participants who received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Up to 28 days
    End point values
    3.5 mg/kg POS (2-7 years old) 3.5 mg/kg POS (7-17 years old) 4.5 mg/kg POS (2-7 years old) 4.5 mg/kg POS (7-17 years old) 6 mg/kg POS (2-7 years old) 6 mg/kg POS (7-17 years old)
    Number of subjects analysed
    14
    21
    15
    16
    20
    29
    Units: Participants
    3
    3
    0
    2
    4
    6
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    14 days after end of treatment (up to day 42)
    Adverse event reporting additional description
    All participants who received at least one dose of study drug. Participants were followed for survival up to 110 days; and deaths that occurred outside of the timeframe for adverse event reporting were recorded in the Disposition
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    3.5 mg/kg posaconazole (2-<7 years old)
    Reporting group description
    Children 2 to less than 7 years of age received posaconazole (POS) at 3.5 mg/kg by intravenous (IV) solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 3.5 mg/kg POS once daily by powder for oral suspension (PFS) for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    3.5 mg/kg posaconazole (7-17 years old)
    Reporting group description
    Children 7 to 17 years of age received POS at 3.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 3.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    4.5 mg/kg posaconazole (2-<7 years old)
    Reporting group description
    Children 2 to less than 7 years of age received posaconazole (POS) at 4.5 mg/kg by intravenous (IV) solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 4.5 mg/kg POS once daily by powder for oral suspension (PFS) for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    4.5 mg/kg posaconazole (7-17 years old)
    Reporting group description
    Children 7 to 17 years of age received POS at 4.5 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 4.5 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    6.0 mg/kg posaconazole (2-<7 years old)
    Reporting group description
    Children 2 to less than 7 years of age received posaconazole (POS) at 6 mg/kg by intravenous (IV) solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 6 mg/kg POS once daily by powder for oral suspension (PFS) for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Reporting group title
    6.0 mg/kg posaconazole (7-17 years old)
    Reporting group description
    Children 7 to 17 years of age received POS at 6 mg/kg by IV solution twice on Day 1, then once daily on Days 2-10. This was followed by treatment with 6 mg/kg POS once daily by PFS for a minimum of 10 days; or, if they were unwilling or unable to tolerate POS PFS, continued treatment with POS IV.

    Serious adverse events
    3.5 mg/kg posaconazole (2-<7 years old) 3.5 mg/kg posaconazole (7-17 years old) 4.5 mg/kg posaconazole (2-<7 years old) 4.5 mg/kg posaconazole (7-17 years old) 6.0 mg/kg posaconazole (2-<7 years old) 6.0 mg/kg posaconazole (7-17 years old)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 14 (21.43%)
    8 / 21 (38.10%)
    4 / 15 (26.67%)
    5 / 16 (31.25%)
    3 / 20 (15.00%)
    8 / 29 (27.59%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    2
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Vascular disorders
    Capillary leak syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Venoocclusive disease
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Engraftment syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Transplant rejection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 21 (9.52%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Cardiomyopathy
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Hypoxia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory failure
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Nervous system disorders
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Presyncope
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Stomatitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic lesion
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Venoocclusive liver disease
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Musculoskeletal and connective tissue disorders
    Chest wall haematoma
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Infections and infestations
    Adenovirus infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Cystitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Device related infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterobacter infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Fungal infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Herpes zoster
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Pneumonia viral
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Streptococcal sepsis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Systemic mycosis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    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
    Urinary tract infection viral
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    3.5 mg/kg posaconazole (2-<7 years old) 3.5 mg/kg posaconazole (7-17 years old) 4.5 mg/kg posaconazole (2-<7 years old) 4.5 mg/kg posaconazole (7-17 years old) 6.0 mg/kg posaconazole (2-<7 years old) 6.0 mg/kg posaconazole (7-17 years old)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 14 (92.86%)
    20 / 21 (95.24%)
    15 / 15 (100.00%)
    16 / 16 (100.00%)
    19 / 20 (95.00%)
    29 / 29 (100.00%)
    Vascular disorders
    Capillary leak syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Flushing
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Haematoma
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Hyperaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Hypertension
         subjects affected / exposed
    5 / 14 (35.71%)
    2 / 21 (9.52%)
    2 / 15 (13.33%)
    1 / 16 (6.25%)
    6 / 20 (30.00%)
    4 / 29 (13.79%)
         occurrences all number
    5
    2
    2
    1
    6
    4
    Hypotension
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    2 / 16 (12.50%)
    1 / 20 (5.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    2
    1
    2
    Pallor
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    Phlebitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Venoocclusive disease
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    2
    0
    1
    0
    0
    2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    2 / 20 (10.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    0
    2
    3
    Engraftment syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Graft versus host disease
         subjects affected / exposed
    2 / 14 (14.29%)
    2 / 21 (9.52%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    2
    2
    0
    1
    0
    1
    Graft versus host disease in gastrointestinal tract
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    Graft versus host disease in liver
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Graft versus host disease in skin
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 21 (9.52%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    2 / 20 (10.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    2
    0
    1
    2
    1
    Hypogammaglobulinaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    2 / 20 (10.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Immunodeficiency
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Immunodeficiency common variable
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Serum sickness
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Axillary pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Catheter site erythema
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Catheter site haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Catheter site oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Catheter site pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    Catheter site swelling
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Chills
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Face oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Fatigue
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    1
    0
    0
    0
    1
    General physical health deterioration
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    Generalised oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Granuloma
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Infusion site erythema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Malaise
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Mucosal inflammation
         subjects affected / exposed
    3 / 14 (21.43%)
    9 / 21 (42.86%)
    5 / 15 (33.33%)
    4 / 16 (25.00%)
    5 / 20 (25.00%)
    6 / 29 (20.69%)
         occurrences all number
    3
    10
    5
    4
    5
    6
    Oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    1
    0
    0
    1
    2
    Pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    8 / 14 (57.14%)
    9 / 21 (42.86%)
    6 / 15 (40.00%)
    10 / 16 (62.50%)
    8 / 20 (40.00%)
    8 / 29 (27.59%)
         occurrences all number
    13
    11
    9
    13
    8
    12
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Anxiety
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    Depressed mood
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Depression
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Irritability
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Reproductive system and breast disorders
    Menorrhagia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Metrorrhagia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Perineal erythema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Perineal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Scrotal oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Testicular oedema
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Vulvovaginal inflammation
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Vulvovaginal pruritus
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Allergic transfusion reaction
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Buttock injury
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Eye contusion
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Head injury
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Infusion related reaction
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    Procedural pain
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Scratch
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Transfusion reaction
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    1
    1
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    5 / 29 (17.24%)
         occurrences all number
    0
    1
    1
    0
    1
    5
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    1 / 15 (6.67%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    5 / 29 (17.24%)
         occurrences all number
    0
    1
    1
    1
    0
    6
    BK polyomavirus test positive
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Bacterial test positive
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Blood albumin decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    2 / 16 (12.50%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    1
    0
    2
    0
    0
    Blood calcium decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    Blood culture positive
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Blood immunoglobulin G decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Blood magnesium decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Blood phosphorus decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Blood potassium decreased
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 21 (9.52%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    2
    0
    1
    0
    0
    Blood potassium increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    Blood urea increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Blood uric acid decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Blood uric acid increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Breath sounds abnormal
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Cytomegalovirus test positive
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Drug level increased
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 21 (9.52%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Fibrin D dimer increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Fluid balance positive
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Oxygen saturation decreased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    1
    0
    2
    Platelet count decreased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    0
    0
    2
    1
    2
    Pulmonary arterial pressure increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Red blood cells urine positive
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Transaminases increased
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 21 (4.76%)
    1 / 15 (6.67%)
    3 / 16 (18.75%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    1
    3
    0
    0
    Viral test positive
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vitamin D decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Weight increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    White blood cell count decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Pericardial effusion
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Sinus bradycardia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Sinus tachycardia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Tachycardia
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 21 (9.52%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    2
    1
    0
    1
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 21 (0.00%)
    4 / 15 (26.67%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    3 / 29 (10.34%)
         occurrences all number
    2
    0
    4
    1
    0
    3
    Dysphonia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Dyspnoea
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 21 (9.52%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    2
    0
    1
    0
    1
    Epistaxis
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 21 (4.76%)
    1 / 15 (6.67%)
    5 / 16 (31.25%)
    1 / 20 (5.00%)
    3 / 29 (10.34%)
         occurrences all number
    4
    1
    1
    8
    1
    4
    Haemoptysis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hypoxia
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 21 (9.52%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    2
    0
    1
    1
    1
    Increased viscosity of bronchial secretion
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Lung infiltration
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    3 / 29 (10.34%)
         occurrences all number
    0
    1
    1
    0
    0
    3
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pleural effusion
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Pleuritic pain
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pulmonary oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Rales
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Tachypnoea
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Tonsillar exudate
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Agranulocytosis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Anaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 21 (4.76%)
    1 / 15 (6.67%)
    3 / 16 (18.75%)
    2 / 20 (10.00%)
    2 / 29 (6.90%)
         occurrences all number
    4
    1
    2
    4
    2
    3
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Febrile neutropenia
         subjects affected / exposed
    2 / 14 (14.29%)
    3 / 21 (14.29%)
    2 / 15 (13.33%)
    2 / 16 (12.50%)
    7 / 20 (35.00%)
    7 / 29 (24.14%)
         occurrences all number
    2
    3
    2
    2
    7
    8
    Leukopenia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 21 (9.52%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    2
    0
    0
    0
    2
    Pancytopenia
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Splenomegaly
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 21 (9.52%)
    0 / 15 (0.00%)
    2 / 16 (12.50%)
    1 / 20 (5.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    2
    0
    2
    3
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Headache
         subjects affected / exposed
    1 / 14 (7.14%)
    4 / 21 (19.05%)
    0 / 15 (0.00%)
    5 / 16 (31.25%)
    1 / 20 (5.00%)
    5 / 29 (17.24%)
         occurrences all number
    1
    4
    0
    6
    1
    7
    Hypoaesthesia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Hypotonia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Intention tremor
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Myoclonus
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Opisthotonus
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Paraesthesia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    2 / 16 (12.50%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    0
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    1
    0
    0
    2
    Dry eye
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    0
    0
    1
    1
    2
    Eye haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Eye irritation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Eye pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Eyelid oedema
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    0
    0
    0
    0
    2
    Ocular hyperaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Periorbital oedema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Photophobia
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Vision blurred
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Visual impairment
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Ear and labyrinth disorders
    Ear haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Ear pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Tinnitus
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Abdominal distension
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    2 / 14 (14.29%)
    2 / 21 (9.52%)
    2 / 15 (13.33%)
    6 / 16 (37.50%)
    2 / 20 (10.00%)
    5 / 29 (17.24%)
         occurrences all number
    2
    2
    2
    8
    2
    7
    Abdominal pain upper
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 21 (9.52%)
    2 / 15 (13.33%)
    0 / 16 (0.00%)
    2 / 20 (10.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    2
    2
    0
    2
    2
    Anal fissure
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 21 (9.52%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    Anal inflammation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Anorectal discomfort
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Anorectal disorder
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Aphthous ulcer
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Ascites
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Colitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Constipation
         subjects affected / exposed
    3 / 14 (21.43%)
    2 / 21 (9.52%)
    2 / 15 (13.33%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    4 / 29 (13.79%)
         occurrences all number
    3
    2
    2
    1
    0
    4
    Diarrhoea
         subjects affected / exposed
    5 / 14 (35.71%)
    2 / 21 (9.52%)
    5 / 15 (33.33%)
    4 / 16 (25.00%)
    5 / 20 (25.00%)
    4 / 29 (13.79%)
         occurrences all number
    5
    2
    5
    4
    6
    5
    Dyspepsia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Dysphagia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Faeces hard
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Gingival bleeding
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Gingival pain
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Glossodynia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Haematemesis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Haematochezia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Lip dry
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Lip pruritus
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Loose tooth
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Mouth ulceration
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nausea
         subjects affected / exposed
    1 / 14 (7.14%)
    4 / 21 (19.05%)
    1 / 15 (6.67%)
    3 / 16 (18.75%)
    2 / 20 (10.00%)
    7 / 29 (24.14%)
         occurrences all number
    1
    5
    1
    5
    2
    9
    Odynophagia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Oesophagitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Oral disorder
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Oral mucosal blistering
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Oral mucosal exfoliation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Oral pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Rectal haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Scalloped tongue
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 21 (9.52%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    3 / 20 (15.00%)
    6 / 29 (20.69%)
         occurrences all number
    0
    2
    0
    1
    3
    6
    Subileus
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Tongue haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Tooth loss
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Toothache
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Vomiting
         subjects affected / exposed
    4 / 14 (28.57%)
    6 / 21 (28.57%)
    2 / 15 (13.33%)
    6 / 16 (37.50%)
    6 / 20 (30.00%)
    6 / 29 (20.69%)
         occurrences all number
    6
    9
    3
    8
    8
    13
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Cystitis haemorrhagic
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    1
    1
    1
    Dysuria
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Glycosuria
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Haematuria
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Micturition urgency
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nephropathy toxic
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Tubulointerstitial nephritis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Urinary retention
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Hepatobiliary disorders
    Hepatomegaly
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Jaundice
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Alopecia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    0
    Blister
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Dermatitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Dermatitis atopic
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Dermatitis bullous
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Dermatitis contact
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Dermatitis diaper
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Drug eruption
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Dry skin
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Erythema
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    1 / 16 (6.25%)
    3 / 20 (15.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    1
    4
    1
    Erythema multiforme
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Macule
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Night sweats
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Palmar erythema
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Papule
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Petechiae
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 21 (4.76%)
    1 / 15 (6.67%)
    2 / 16 (12.50%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    1
    1
    2
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    1 / 15 (6.67%)
    5 / 16 (31.25%)
    4 / 20 (20.00%)
    7 / 29 (24.14%)
         occurrences all number
    0
    1
    1
    5
    5
    7
    Pruritus allergic
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Rash
         subjects affected / exposed
    2 / 14 (14.29%)
    4 / 21 (19.05%)
    3 / 15 (20.00%)
    2 / 16 (12.50%)
    4 / 20 (20.00%)
    3 / 29 (10.34%)
         occurrences all number
    3
    4
    4
    2
    6
    3
    Rash generalised
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    2 / 20 (10.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Rash macular
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Rash pruritic
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Skin burning sensation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Skin exfoliation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Skin lesion
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Skin mass
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Skin ulcer
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Swelling face
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    Urticaria
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Back pain
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    3 / 16 (18.75%)
    1 / 20 (5.00%)
    3 / 29 (10.34%)
         occurrences all number
    0
    1
    0
    4
    1
    3
    Bone pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Joint range of motion decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Muscle tightness
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Musculoskeletal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Myalgia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    3 / 29 (10.34%)
         occurrences all number
    0
    1
    0
    1
    0
    3
    Pain in extremity
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 21 (4.76%)
    1 / 15 (6.67%)
    3 / 16 (18.75%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    2
    5
    1
    0
    Pain in jaw
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Soft tissue swelling
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 14 (14.29%)
    4 / 21 (19.05%)
    3 / 15 (20.00%)
    1 / 16 (6.25%)
    3 / 20 (15.00%)
    4 / 29 (13.79%)
         occurrences all number
    2
    4
    3
    1
    3
    4
    Fluid intake reduced
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Fluid retention
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    1
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Hypernatraemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    2 / 20 (10.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    Hypocalcaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Hypochloraemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    0
    1
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    3 / 16 (18.75%)
    3 / 20 (15.00%)
    7 / 29 (24.14%)
         occurrences all number
    2
    0
    1
    3
    3
    8
    Hypomagnesaemia
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 21 (4.76%)
    2 / 15 (13.33%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    4 / 29 (13.79%)
         occurrences all number
    2
    1
    3
    1
    0
    5
    Hyponatraemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    0
    1
    0
    Hypophagia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    3 / 20 (15.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    1
    0
    3
    1
    Magnesium deficiency
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Metabolic acidosis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Vitamin D deficiency
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Infections and infestations
    Adenovirus infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    BK virus infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Bacteraemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Bacterial infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Clostridial infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Corona virus infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Cystitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    3 / 15 (20.00%)
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    0
    3
    1
    1
    2
    Device related infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Ear infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Endocarditis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Enterobacter bacteraemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Epstein-Barr virus infection
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 21 (4.76%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    1
    1
    0
    1
    2
    Escherichia sepsis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Gingivitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Hepatitis E
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Human bocavirus infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    Klebsiella bacteraemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Klebsiella infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Localised infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Lung infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Mucosal infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    1 / 15 (6.67%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Oral herpes
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Paronychia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Pneumonia parainfluenzae viral
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Proctitis herpes
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    1 / 16 (6.25%)
    0 / 20 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Rhinitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    Rhinovirus infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Sepsis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 21 (4.76%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 21 (0.00%)
    0 / 15 (0.00%)
    0 / 16 (0.00%)
    0 / 20 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Staphylococcal infection