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    Clinical Trial Results:
    An open phase I/IIa trial to investigate the maximum tolerated dose, safety, pharmacokinetics and efficacy of intravenous BI 6727 as monotherapy or in combination with subcutaneous cytarabine in patients with acute myeloid leukaemia

    Summary
    EudraCT number
    		 2008-003617-27
    Trial protocol
    		 DE   BE   AT  
    Global end of trial date
    23 Apr 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Apr 2022
    First version publication date
    22 Apr 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    1230.4
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00804856
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Boehringer Ingelheim
    Sponsor organisation address
    Binger Strasse 173, Ingelheim am Rhein, Germany,
    Public contact
    Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com
    Scientific contact
    Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    05 May 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    09 Mar 2012
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Apr 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the maximum tolerated dose (MTD), safety, pharmacokinetics and efficacy of volasertib monotherapy and volasertib in combination with low dose cytarabine (LDAC) in patients with acute myeloid leukaemia (AML)
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. If a subject continued to take trial medication, close monitoring was adhered to and all adverse events recorded. Rules were implemented in all trials whereby doses would be reduced if required. Thereafter, if further events were reported, the subject would be withdrawn from the trial. Symptomatic treatment of tumour associated symptoms were allowed throughout.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Dec 2008
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 2
    Country: Number of subjects enrolled
    Belgium: 20
    Country: Number of subjects enrolled
    Canada: 7
    Country: Number of subjects enrolled
    Germany: 126
    Country: Number of subjects enrolled
    France: 23
    Country: Number of subjects enrolled
    Italy: 8
    Country: Number of subjects enrolled
    Norway: 7
    Worldwide total number of subjects
    193
    EEA total number of subjects
    186
    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)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    18
    From 65 to 84 years
    169
    85 years and over
    6

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Open-label, randomized, dose escalation study. In this trial 180 patients were entered and randomised. However 3 patients were entered but not treated in Phase I and 2 patients were not treated in Phase II. Thus total 175 patients were treated in this trial.

    Pre-assignment
    Screening details
    		 Patients were assigned to two treatment schedules (A and B) in the phase I part of the trial (dose escalation phase to determine maximum tolerated dose (MTD)). In the phase IIa part of the trial (after MTD was determined), patients were randomised to two treatment schedules (A and C).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    This trial was conducted according to an open-label design.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Phase I Schedule A. Volasertib 150 mg+LDAC
    Arm description
    		 Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Low-dose cytarabine (LDAC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Low-dose cytarabine (LDAC) 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Arm title
    		 Phase I Schedule A. Volasertib 200 mg+LDAC
    Arm description
    		 Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Low-dose cytarabine (LDAC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Low-dose cytarabine (LDAC) 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Arm title
    		 Phase I Schedule A. Volasertib 250 mg+LDAC
    Arm description
    		 Volasertib 250 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Investigational medicinal product name
    Low-dose cytarabine (LDAC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Low-dose cytarabine (LDAC) 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Arm title
    		 Phase I Schedule A. Volasertib 300 mg+LDAC
    Arm description
    		 Volasertib 300 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 300 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Investigational medicinal product name
    Low-dose cytarabine (LDAC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Low-dose cytarabine (LDAC) 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Arm title
    		 Phase I Schedule A. Volasertib 350 mg+LDAC
    Arm description
    		 Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Investigational medicinal product name
    Low-dose cytarabine (LDAC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Low-dose cytarabine (LDAC) 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Arm title
    		 Phase I Schedule A. Volasertib 400 mg+LDAC
    Arm description
    		 Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Investigational medicinal product name
    Low-dose cytarabine (LDAC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Low-dose cytarabine (LDAC) 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Arm title
    		 Phase I Schedule B. Volasertib 150 mg
    Arm description
    		 Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Arm title
    		 Phase I Schedule B. Volasertib 200 mg
    Arm description
    		 Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Arm title
    		 Phase I Schedule B. Volasertib 350 mg
    Arm description
    		 Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Arm title
    		 Phase I Schedule B. Volasertib 400 mg
    Arm description
    		 Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Arm title
    		 Phase I Schedule B. Volasertib 450 mg
    Arm description
    		 Volasertib 450 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 450 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Arm title
    		 Phase I Schedule B. Volasertib 500 mg
    Arm description
    		 Volasertib 500 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 500 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Arm title
    		 Phase I Schedule B. Volasertib 550 mg
    Arm description
    		 Volasertib 550 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 550 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Arm title
    		 Phase II Schedule C. LDAC
    Arm description
    		 Low-dose cytarabine (LDAC) monotherapy 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 days treatment cycle.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Low-dose cytarabine (LDAC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Low-dose cytarabine (LDAC) 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Arm title
    		 Phase II Schedule A. Volasertib 350 mg+LDAC
    Arm description
    		 Volasertib 350 milligram (mg) on Days 1 and 15 (28-day cycle) administered by Intravenous Infusion (IV) over 60 minutes and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 days treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Low-dose cytarabine (LDAC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Low-dose cytarabine (LDAC) 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Investigational medicinal product name
    Volasertib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle)

    Number of subjects in period 1 [1]
    		Phase I Schedule A. Volasertib 150 mg+LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 550 mg Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC
    Started
    4
    3
    5
    9
    8
    3
    11
    2
    5
    6
    23
    5
    4
    45
    42
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    4
    3
    5
    9
    8
    3
    11
    2
    5
    6
    23
    5
    4
    45
    42
         Other Adverse Event
    1
    1
    1
    2
    2
    1
    3
    -
    -
    1
    5
    2
    -
    6
    13
         Dose Limiting Toxicity (DLT)
    -
    -
    -
    -
    1
    -
    -
    -
    -
    -
    -
    -
    -
    -
    1
         Progressive Disease
    3
    2
    4
    6
    4
    1
    8
    2
    4
    5
    12
    2
    2
    26
    20
         Other reason than listed above
    -
    -
    -
    -
    -
    1
    -
    -
    1
    -
    3
    1
    1
    10
    3
         Refused to continue medication
    -
    -
    -
    1
    1
    -
    -
    -
    -
    -
    3
    -
    1
    1
    5
         Non compliance with protocol
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    2
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of the 193 enrolled subjects, 175 were treated and displayed here.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Phase I Schedule A. Volasertib 150 mg+LDAC
    Reporting group description
    		 Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 200 mg+LDAC
    Reporting group description
    		 Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 250 mg+LDAC
    Reporting group description
    		 Volasertib 250 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 300 mg+LDAC
    Reporting group description
    		 Volasertib 300 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 350 mg+LDAC
    Reporting group description
    		 Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 400 mg+LDAC
    Reporting group description
    		 Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule B. Volasertib 150 mg
    Reporting group description
    		 Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 200 mg
    Reporting group description
    		 Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 350 mg
    Reporting group description
    		 Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 400 mg
    Reporting group description
    		 Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 450 mg
    Reporting group description
    		 Volasertib 450 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 500 mg
    Reporting group description
    		 Volasertib 500 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 550 mg
    Reporting group description
    		 Volasertib 550 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase II Schedule C. LDAC
    Reporting group description
    		 Low-dose cytarabine (LDAC) monotherapy 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 days treatment cycle.

    Reporting group title
    Phase II Schedule A. Volasertib 350 mg+LDAC
    Reporting group description
    		 Volasertib 350 milligram (mg) on Days 1 and 15 (28-day cycle) administered by Intravenous Infusion (IV) over 60 minutes and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 days treatment cycle.

    Reporting group values
    		 Phase I Schedule A. Volasertib 150 mg+LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 550 mg Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC Total
    Number of subjects
    		 4 3 5 9 8 3 11 2 5 6 23 5 4 45 42 175
    Age categorical
    Treated Set: All patients in Phase I who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason. For the Phase II part, the treated set (Phase II) was defined as all patients in Phase II who received at least a single dose of either Volasertib or LDAC.
    Units: participants
        In utero
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 1 1 1 2 1 0 0 0 0 1 7 1 0 2 0 17
        From 65-84 years
    		 3 2 4 7 7 3 11 2 5 5 16 4 4 41 40 154
        85 years and over
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 2 2 4
    Age Continuous
    Treated Set: All patients in Phase I who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason. For the Phase II part, the treated set (Phase II) was defined as all patients in Phase II who received at least a single dose of either Volasertib or LDAC.
    Units: years
        arithmetic mean (standard deviation)
    		 69.5 ( 12.1 ) 67.0 ( 3.0 ) 71.2 ( 6.8 ) 67.9 ( 12.0 ) 72.5 ( 6.1 ) 73.3 ( 7.6 ) 73.5 ( 3.9 ) 73.0 ( 4.2 ) 70.6 ( 2.9 ) 65.2 ( 20.1 ) 68.2 ( 7.7 ) 66.4 ( 7.3 ) 69.8 ( 4.1 ) 75.2 ( 5.5 ) 75.6 ( 4.9 ) -
    Gender, Male/Female
    Treated Set: All patients in Phase I who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason. For the Phase II part, the treated set (Phase II) was defined as all patients in Phase II who received at least a single dose of either Volasertib or LDAC.
    Units: Participants
        Female
    		 2 0 2 3 3 1 3 1 3 2 16 1 3 20 19 79
        Male
    		 2 3 3 6 5 2 8 1 2 4 7 4 1 25 23 96
    Race (NIH/OMB)
    Treated Set: All patients in Phase I who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason. For the Phase II part, the treated set (Phase II) was defined as all patients in Phase II who received at least a single dose of either Volasertib or LDAC.
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 1
        Asian
    		 0 0 1 1 0 0 0 0 0 0 0 0 0 1 1 4
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        White
    		 4 3 4 8 8 3 11 2 5 6 21 5 4 35 34 153
        More than one race
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0 0 0 0 0 0 0 2 0 0 8 7 17

    End points

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    End points reporting groups
    Reporting group title
    Phase I Schedule A. Volasertib 150 mg+LDAC
    Reporting group description
    		 Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 200 mg+LDAC
    Reporting group description
    		 Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 250 mg+LDAC
    Reporting group description
    		 Volasertib 250 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 300 mg+LDAC
    Reporting group description
    		 Volasertib 300 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 350 mg+LDAC
    Reporting group description
    		 Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 400 mg+LDAC
    Reporting group description
    		 Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule B. Volasertib 150 mg
    Reporting group description
    		 Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 200 mg
    Reporting group description
    		 Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 350 mg
    Reporting group description
    		 Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 400 mg
    Reporting group description
    		 Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 450 mg
    Reporting group description
    		 Volasertib 450 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 500 mg
    Reporting group description
    		 Volasertib 500 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 550 mg
    Reporting group description
    		 Volasertib 550 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase II Schedule C. LDAC
    Reporting group description
    		 Low-dose cytarabine (LDAC) monotherapy 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 days treatment cycle.

    Reporting group title
    Phase II Schedule A. Volasertib 350 mg+LDAC
    Reporting group description
    		 Volasertib 350 milligram (mg) on Days 1 and 15 (28-day cycle) administered by Intravenous Infusion (IV) over 60 minutes and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 days treatment cycle.

    Subject analysis set title
    Phase I Schedule A. Volasertib+LDAC
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    PVolasertib escalating dose on Days 1 and 15 (28-day cycle). Dose escalation in 50 milligram (mg) steps up to 400 mg, with a starting dose of 150 mg and LDAC 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle until the patient met criteria for stopping study medication during the MTD evaluation period.

    Subject analysis set title
    Phase I Schedule B. Volasertib
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Volasertib escalating dose on Days 1 and 15 (28-day cycle). Dose escalation in 50 milligram (mg) steps from an initial starting dose of 150 mg; dose escalation stopped at 200 mg and then restarted from the MTD dose in Schedule A (350 mg); dose was escalated up to 550 mg. Volasertib administered by Intravenous Infusion (IV) over 60 minutes.

    Subject analysis set title
    Phase II Combined. Schedule A and C
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Volasertib escalating dose on Days 1 and 15 (28-day cycle). Dose escalation in 50 milligram (mg) steps up to 400 mg, with a starting dose of 150 mg. Volasertib 350 mg on Days 1+15 (28-day cycle) administered by Intravenous Infusion (IV) over 60 minutes and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Subject analysis set title
    Dose norm Volasertib+LDAC (Phase I A). 150-400 mg Volasertib
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Volasertib 150 to 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle. Dose groups of Phase I were combined by dose normalizing as pre specified in the study protocol.

    Subject analysis set title
    Phase I+II Volasertib 350 mg+LDAC
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Phase I+II: Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Primary: Phase I: Maximum Tolerated Dose (MTD) of Volasertib in Combination with LDAC (schedule A) and Volasertib monotherapy (schedule B)

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    End point title
    		 Phase I: Maximum Tolerated Dose (MTD) of Volasertib in Combination with LDAC (schedule A) and Volasertib monotherapy (schedule B) [1]
    End point description
    To determine the Maximum tolerated dose (MTD), dose escalation was conducted following 3+3 design with de-escalation. The MTD was defined as the highest dose at which 6 patients had been treated and less than 2 patients experienced a Dose limiting toxicity (DLT), first cycle only. DLT is defined as drug related Common terminology criteria for adverse events (CTCAE) grade ≥ 3 nonhaematological toxicity (excluding: untreated nausea, untreated vomiting, CTCAE grade 3 untreated diarrhoea, CTCAE grade 3 "febrile neutropenia" and CTCAE grade 3 "infection with grade 3 or 4 neutrophils"). In patients with CRi or PR, persistent CTCAE grade 4 neutropenia or thrombocytopenia until three weeks after the end of the treatment cycle were regarded a DLT. Treated Set-phase I part: all patients who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason.
    End point type
    Primary
    End point timeframe
    First Treatment cycle, up to 28 days.
    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: As pre-specified in the protocol this end point only analyses the Phase I arms.
    End point values
    		 Phase I Schedule A. Volasertib+LDAC Phase I Schedule B. Volasertib
    Number of subjects analysed
    32
    56
    Units: milligram (mg)
    350
    450
    No statistical analyses for this end point

    Primary: Phase II: Number of patients with Objective Response (Complete remission (CR) + Complete remission with incomplete blood count recovery (CRi))

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    End point title
    		 Phase II: Number of patients with Objective Response (Complete remission (CR) + Complete remission with incomplete blood count recovery (CRi)) [2]
    End point description
    Phase II: Number of patients with Objective Response (Complete remission (CR) + Complete remission with incomplete blood count recovery (CRi)). Treated set-phase II part: Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC.
    End point type
    Primary
    End point timeframe
    The best overall response recorded during the time period from the start of the treatment until end of the treatment period, progression or death (whichever was earlier), up to 869 days.
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point only analyses the Phase II arms.
    End point values
    		 Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects analysed
    45
    42
    Units: Participants
    6
    13
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Analysis for Objective Response. Ratio calculated as Phase II Schedule A Volasertib 350mg+LDAC divided by Phase II Schedule C LDAC.
    Comparison groups
    Phase II Schedule C. LDAC v Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0523
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 8.58

    Primary: Phase I: Number of Participants with Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

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    End point title
    		 Phase I: Number of Participants with Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD) [3] [4]
    End point description
    A DLT was defined as a drug related CTCAE (Common Toxicity Criteria for Adverse Events) Grade ≥3 non-haematological toxicity (excluding untreated nausea, untreated vomiting, Grade 3 untreated diarrhea, Grade 3 febrile neutropenia, and Grade 3 infection with Grade 3 or 4 neutrophils). In patients with CRi (Complete Remission with Incomplete Blood Count Recovery) or PR (Partial Remission), persistent Grade 4 neutropenia or thrombocytopenia for 3 weeks after the end of the treatment cycle was regarded as a DLT unless the respective Grade 4 cytopenia was preexistent. In patients who required platelet substitution to maintain a Grade <4 before treatment, a Grade 4 thrombocytopenia after treatment did not constitute a DLT. Treated Set-Phase I part: Treated Set was defined as all patients who received at least a single dose of either Volasertib (BI 6727) or LDAC (Low-Dose Cytarabine), including patients who were replaced for any reason.
    End point type
    Primary
    End point timeframe
    First Treatment cycle, up to 28 days.
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As pre-specified in the protocol this end point only analyses the Phase I arms.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point only analyses the Phase I arms.
    End point values
    		 Phase I Schedule A. Volasertib 150 mg+LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 550 mg Phase I Schedule A. Volasertib+LDAC Phase I Schedule B. Volasertib
    Number of subjects analysed
    4
    3
    5
    9
    8
    3
    11
    2
    5
    6
    23
    5
    4
    32
    56
    Units: Participants
    0
    0
    0
    1
    1
    2
    1
    0
    0
    1
    1
    2
    2
    4
    7
    No statistical analyses for this end point

    Secondary: Best Overall Response

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    End point title
    		 Best Overall Response
    End point description
    Best overall response: The best overall response recorded during the time period from the start of the treatment until end of the treatment period, progression or death (whichever was earlier). Possible responses for best overall response were: Complete remission (CR), Complete remission with incomplete blood count recovery (CRi), Partial remission (PR), no change, aplasia, Indeterminate, Progressive disease (PD), Not evaluable or missing. Patients dying before any assessment were classified as PD for best overall response. The number of participants for each response is reported. Treated Set-phase I part: Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason. Phase II part, the Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC.
    End point type
    Secondary
    End point timeframe
    The best overall response recorded during the time period from the start of the treatment until end of the treatment period, progression or death (whichever was earlier), up to 869 days.
    End point values
    		 Phase I Schedule A. Volasertib 150 mg+LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 550 mg Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib+LDAC Phase I Schedule B. Volasertib Phase II Combined. Schedule A and C
    Number of subjects analysed
    4
    3
    5
    9
    8
    3
    11
    2
    5
    6
    23
    5
    4
    45
    42
    32
    56
    87
    Units: Participants
        Complete remission
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    6
    2
    0
    9
        CRi
    0
    2
    0
    1
    1
    0
    0
    0
    1
    2
    2
    0
    0
    3
    7
    4
    5
    10
        Partial remission
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    2
    0
    1
    2
    2
    0
    4
    4
        No change
    2
    1
    2
    1
    1
    1
    4
    0
    2
    2
    7
    3
    0
    18
    15
    8
    18
    33
        Aplasia
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    3
    1
    1
    0
    0
    0
    6
    0
        Indeterminate
    0
    0
    0
    2
    3
    1
    1
    0
    0
    0
    0
    0
    0
    3
    5
    6
    1
    8
        Progressive disease
    2
    0
    1
    3
    3
    1
    6
    2
    1
    1
    7
    1
    1
    14
    7
    10
    19
    21
        Not evaluable
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    2
    0
    1
    2
    0
    1
    3
    2
        Missing
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Phase I: Number of Patients with Objective Response: Complete remission or Complete remission with incomplete blood count recovery (CR+CRi)

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    End point title
    		 Phase I: Number of Patients with Objective Response: Complete remission or Complete remission with incomplete blood count recovery (CR+CRi) [5]
    End point description
    Phase I: Objective Response (yes/no): yes=Best Overall Response of Complete remission (CR) or Complete remission with incomplete blood count recovery (CRi), no=all others. Treated Set-phase I part: Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason.
    End point type
    Secondary
    End point timeframe
    The best overall response recorded during the time period from the start of the treatment until end of the treatment period, progression or death (whichever was earlier), up to 594 days.
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point only analyses the Phase I arms.
    End point values
    		 Phase I Schedule A. Volasertib 150 mg+LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 550 mg Phase I Schedule A. Volasertib+LDAC Phase I Schedule B. Volasertib
    Number of subjects analysed
    4
    3
    5
    9
    8
    3
    11
    2
    5
    6
    23
    5
    4
    32
    56
    Units: Participants
    0
    2
    2
    1
    1
    0
    0
    0
    1
    2
    2
    0
    0
    6
    5
    No statistical analyses for this end point

    Secondary: Phase II: Event Free Survival

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    End point title
    		 Phase II: Event Free Survival [6]
    End point description
    Event-free survival (EFS) [days] was the shortest duration of the following: (a) Date of assessment indicating PD on the response page of the eCRF (Electronic Case Report Form) – date of randomisation + 1 day (b) Date of assessment indicating clinical progressive disease (PD) on the disease or responses pages of the of eCRF– date of randomisation + 1 day (c) Date of assessment indicating PD on the patient status page of the eCRF – date of randomisation +1 day (for patients who had not been censored before this time point) (d) Death date – date of randomisation +1 day. Patients not being assessed PD, clinical PD, or death during the trial were censored. EFS was analysed with the Kaplan-Meier method for each of the treatment arms. Treated Set-Phase II part: Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC.
    End point type
    Secondary
    End point timeframe
    The patients that entered the trial, and measured from the date of randomization to the date of disease progression (treatment failure), relapse or death from any cause, whichever occurred first, up to 1000 days..
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point only analyses the Phase II arms.
    End point values
    		 Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects analysed
    45
    42
    Units: Days
        median (inter-quartile range (Q1-Q3))
    69.0 (27 to 215)
    169.0 (39 to 470)
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    An exploratory (non-stratified) logrank test was used to compare the different treatment arms.
    Comparison groups
    Phase II Schedule C. LDAC v Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 [7]
    P-value
    		 = 0.0208
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 0.92
    Notes
    [7] - Ratio calculated as Phase II Schedule A Volasertib 350mg+LDAC divided by Phase II Schedule C LDAC.

    Secondary: Phase II: Overall Survival

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    End point title
    		 Phase II: Overall Survival [8]
    End point description
    Overall survival [days] = (date of death - date of randomisation + 1 day), for patients with known date of death. Overall survival (censored) [days] = (date of last trial visit or follow-up - date of randomisation + 1 day), for patients who were still alive at time of database lock. Overall survival (OS) was analysed with the Kaplan-Meier method for each of the treatment arms. Treated Set-Phase II part: Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC.
    End point type
    Secondary
    End point timeframe
    The patients that entered the trial, and measured from the date of randomisation until death from any cause, up to 1100 days..
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point only analyses the Phase II arms.
    End point values
    		 Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects analysed
    45
    42
    Units: Days
        median (inter-quartile range (Q1-Q3))
    158.0 (78 to 347)
    245.0 (73 to 689)
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    An exploratory (non-stratified) logrank test was used to compare the different treatment arms.
    Comparison groups
    Phase II Schedule C. LDAC v Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects included in analysis
    87
    Analysis specification
    Pre-specified
    Analysis type
    		 [9]
    P-value
    		 = 0.0465
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 1
    Notes
    [9] - Ratio calculated as Phase II Schedule A Volasertib 350mg+LDAC divided by Phase II Schedule C LDAC.

    Secondary: Phase II: Relapse - Free Survival

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    End point title
    		 Phase II: Relapse - Free Survival [10]
    End point description
    Relapse-free survival [days] = (date of first recurrence of disease or death after entering the trial – date of first occurrence of CR or CRi after entering the trial+ 1 day) for patients with a recurrence (this value should be positive). Relapse-free survival (censored) [days] = (date of last trial visit or follow-up - date of first occurrence of CR or CRi after entering the trial + 1 day) for patients who did not experience recurrence of disease or death at the time of analysis. Patients in Treated Set-Phase II with objective response. Treated Set-Phase II part: Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC.
    End point type
    Secondary
    End point timeframe
    The patients who achieved CR or CRi, and was measured from the date of attaining CR or CRi until the date of disease recurrence or death from any cause, whichever occurred first, up to 900 days.
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point only analyses the Phase II arms.
    End point values
    		 Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects analysed
    6
    13 [11]
    Units: Days
        median (inter-quartile range (Q1-Q3))
    304.0 (113 to 367)
    563.0 (427 to 99999)
    Notes
    [11] - 99999 = NA, 25% quartile not reached, not enough events occurred.
    No statistical analyses for this end point

    Secondary: Phase II: Remission Duration

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    End point title
    		 Phase II: Remission Duration [12]
    End point description
    Remission duration analysis was defined only for patients who achieved Complete remission (CR) or Complete remission with incomplete blood count recovery (CRi), and was measured from the date of attaining CR or CRi until the date of disease recurrence (relapse). For patients who died without report of relapse, remission duration was censored on the date of death, regardless of cause. Patients in Treated Set-Phase II with objective response. Treated Set-Phase II part: Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC.
    End point type
    Secondary
    End point timeframe
    The patients who achieved CR or CRi, and was measured from the date of attaining CR or CRi until the date of disease recurrence (relapse), up to 900 days.
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point only analyses the Phase II arms.
    End point values
    		 Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects analysed
    6
    13 [13]
    Units: Days
        median (inter-quartile range (Q1-Q3))
    367.0 (113 to 367)
    687.0 (427 to 99999)
    Notes
    [13] - 99999 = NA, 25% quartile not reached, not enough events occurred.
    No statistical analyses for this end point

    Secondary: Phase II: Time to Remission

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    End point title
    		 Phase II: Time to Remission [14]
    End point description
    Time to remission [days] = (date of first occurrence of CR or CRi after entering the trial–date of randomisation + 1 day) for patients with an objective response. Patients in Treated Set-Phase II with objective response. Treated Set-Phase II part: Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC.
    End point type
    Secondary
    End point timeframe
    The patients who achieved CR or CRi, and was measured from the date of attaining CR or CRi until the date of disease recurrence (relapse), up to 158 days.
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point only analyses the Phase II arms.
    End point values
    		 Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects analysed
    6
    13
    Units: Days
        median (full range (min-max))
    63.5 (30 to 125)
    71.0 (29 to 158)
    No statistical analyses for this end point

    Secondary: Best Eastern Co-operative Oncology Group (ECOG) Performance Score from Baseline until End of Treatment

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    End point title
    		 Best Eastern Co-operative Oncology Group (ECOG) Performance Score from Baseline until End of Treatment
    End point description
    ECOG performance score change from baseline to last visit of last cycle = ECOG performance score at last visit of the last cycle – ECOG performance score at baseline. ECOG performance score changes from baseline were also categorised on a 3-point categorical scale: deteriorated (-1), unchanged (0), and improved (1). The number of participants for category of ECOG score change is reported. Treated Set-Phase I part: Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason. Phase II part, the Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC. Only participants with non-missing values are reported.
    End point type
    Secondary
    End point timeframe
    Baseline and End of Treatment (up to 869 days).
    End point values
    		 Phase I Schedule A. Volasertib 150 mg+LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 550 mg Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib+LDAC Phase I Schedule B. Volasertib Phase II Combined. Schedule A and C
    Number of subjects analysed
    4
    3
    5
    5
    8
    2
    10
    2
    5
    6
    22
    5
    3
    42
    39
    27
    53
    81
    Units: Participants
        Unchanged
    3
    1
    5
    2
    5
    1
    9
    1
    0
    4
    14
    2
    3
    22
    15
    17
    33
    37
        Improved
    0
    2
    0
    1
    0
    0
    0
    0
    1
    1
    3
    1
    0
    8
    13
    3
    6
    21
        Deteriorated
    1
    0
    0
    2
    3
    1
    1
    1
    4
    1
    5
    2
    0
    12
    11
    7
    14
    23
    No statistical analyses for this end point

    Secondary: Total Clearance (CL) of Volasertib in Plasma after i.v (Intravenous) Administration of Volasertib

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    End point title
    		 Total Clearance (CL) of Volasertib in Plasma after i.v (Intravenous) Administration of Volasertib [15]
    End point description
    Total Clearance (CL) of Volasertib in Plasma after Intravenous (i.v.) Administration of Volasertib. Pharmacokinetic (PK) set which included all patients in the treated set who had at least 1 evaluable blood sample during cycle 1. Phase I Schedule B Volasertib 200mg+LDAC was not analysed as there was insufficient data, Only participants with non-missing values are reported.
    End point type
    Secondary
    End point timeframe
    Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h, 24h, 96h, 216h, 335:55h, 336:30h, 337h, 337:30h, 338h, 339h, 340h, 648h after first drug administration.
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point only analyses the Phase I and Phase IIA arms.
    End point values
    		 Phase I Schedule A. Volasertib 150 mg+LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 550 mg Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects analysed
    4
    3
    5
    8
    8
    3
    10
    1 [16]
    5
    6
    22
    5
    3
    31
    Units: millilitre/minute (mL/min)
        geometric mean (geometric coefficient of variation)
    1280 ( 52.8 )
    972 ( 26.6 )
    864 ( 27.6 )
    1150 ( 34.4 )
    1000 ( 36.2 )
    852 ( 49.6 )
    1330 ( 29.3 )
    9999 ( 9999 )
    810 ( 35.1 )
    1120 ( 62.1 )
    920 ( 36.2 )
    1140 ( 38.5 )
    939 ( 93.2 )
    897 ( 42.8 )
    Notes
    [16] - 9999 = not calculable with one subject
    No statistical analyses for this end point

    Secondary: Apparent Volume of Distribution of volasertib at steady state (VSS)

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    End point title
    		 Apparent Volume of Distribution of volasertib at steady state (VSS) [17]
    End point description
    Apparent Volume of Distribution of volasertib at steady state (VSS) following Intravenous (i.v.) administration. Pharmacokinetic (PK) set which included all patients in the treated set who had at least 1 evaluable blood sample during cycle 1. Phase I Schedule B Volasertib 200mg+LDAC was not analysed as there was insufficient data.
    End point type
    Secondary
    End point timeframe
    Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h, 24h, 96h, 216h, 335:55h, 336:30h, 337h, 337:30h, 338h, 339h, 340h, 648h after first drug administration.
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point only analyses the Phase I and Phase IIA arms.
    End point values
    		 Phase I Schedule A. Volasertib 150 mg+LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 550 mg Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects analysed
    4
    3
    5
    8
    8
    3
    10
    1 [18]
    5
    6
    22
    5
    3
    31
    Units: Liter (L)
        geometric mean (geometric coefficient of variation)
    10600 ( 111.0 )
    8640 ( 14.1 )
    7000 ( 26.6 )
    6320 ( 35.9 )
    5270 ( 58.2 )
    4830 ( 56.7 )
    10300 ( 36.3 )
    9999 ( 9999 )
    5800 ( 35.1 )
    7150 ( 70.6 )
    5740 ( 38.7 )
    6360 ( 50.1 )
    5680 ( 81.9 )
    6130 ( 42.0 )
    Notes
    [18] - 9999 = Not calculable with one subject
    No statistical analyses for this end point

    Secondary: Dose normalized maximum measured concentration of cytarabine in plasma (Cmax, norm)

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    End point title
    		 Dose normalized maximum measured concentration of cytarabine in plasma (Cmax, norm) [19]
    End point description
    Cmax, norm: Maximum measured concentration of Cytarabine in plasma. The dose normalisation was done by dividing by the dose applied. Unit: nanogram/milliliter/milligram: ((ng/mL)/mg). Dose groups of Phase I were combined by dose normalizing as pre specified in the study protocol. Pharmacokinetic (PK) set which included all patients in the treated set who had at least 1 evaluable blood sample during cycle 1, Only participants with non-missing values are reported.
    End point type
    Secondary
    End point timeframe
    Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h, 24h, 96h, 216h, 335:55h, 336:30h, 337h, 337:30h, 338h, 339h, 340h, 648h after first drug administration.
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point Phase IA arms were combined and compared to the Phase II C and Phase II A (350 mg) arms.
    End point values
    		 Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC Dose norm Volasertib+LDAC (Phase I A). 150-400 mg Volasertib
    Number of subjects analysed
    40
    41
    32
    Units: (ng/mL)/mg
        geometric mean (geometric coefficient of variation)
    2.36 ( 77.6 )
    2.83 ( 52.8 )
    2.92 ( 61.3 )
    No statistical analyses for this end point

    Secondary: Dose Normalized Area Under the Concentration-Time Curve of Cytarabine in Plasma Over the Time Interval from 0 Extrapolated up to 4 hours

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    End point title
    		 Dose Normalized Area Under the Concentration-Time Curve of Cytarabine in Plasma Over the Time Interval from 0 Extrapolated up to 4 hours [20]
    End point description
    AUC0-4,norm: Area under the concentration-time curve of Cytarabine in plasma over the time interval from zero extrapolated to 4 hours. The dose normalisation was done by dividing by dose applied. Unit: nanogram*hour/milliliter/milligram: ((ng*h/mL)/mg). Dose groups of Phase I were combined by dose normalizing as pre specified in the study protocol. Pharmacokinetic (PK) set which included all patients in the treated set who had at least 1 evaluable blood sample during cycle 1, Only participants with non-missing values are reported.
    End point type
    Secondary
    End point timeframe
    Cycle 1: -0:05 hour (h), 0:30h, 1:00h, 1:30h, 2h, 3h, 4h after first drug administration.
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol this end point Phase IA arms were combined and compared to the Phase II C and Phase II A (350 mg) arms.
    End point values
    		 Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC Dose norm Volasertib+LDAC (Phase I A). 150-400 mg Volasertib
    Number of subjects analysed
    40
    41
    32
    Units: (ng*h/mL)/mg
        geometric mean (geometric coefficient of variation)
    3.94 ( 43.8 )
    4.00 ( 35.6 )
    3.84 ( 30.6 )
    No statistical analyses for this end point

    Secondary: Absolute QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Intervals

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    End point title
    		 Absolute QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Intervals [21]
    End point description
    ECG (electrocardiogram) Measurements: Absolute QTcF (QT Interval (interval from the beginning of the QRS complex to the end of the T wave) Corrected for Heart Rate Using Fridericia's Formula) Intervals. Treated Set-Phase I part: Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason. Only participants with non-missing values are reported. The 350 mg + LDAC arm of phase I and II were combined into one arm to provide maximum information on QT changes and presented together with the Phase I schedule B 450 mg arm, as pre specified in the study protocol.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -14 to -1) and day 1 (1 hour and 24 hours) after start of infusion.
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol only arms with sufficient subject numbers were included in this endpoint.
    End point values
    		 Phase I Schedule B. Volasertib 450 mg Phase I+II Volasertib 350 mg+LDAC
    Number of subjects analysed
    23
    50
    Units: milliseconds (ms)
    arithmetic mean (standard deviation)
        Individual baseline
    412.4 ( 18.7 )
    411.6 ( 20.7 )
        1 hour after start of infusion
    441.1 ( 20.0 )
    430.0 ( 20.4 )
        24 hour after start of infusion
    411.9 ( 18.4 )
    414.0 ( 21.3 )
    No statistical analyses for this end point

    Secondary: QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Change from Baseline at Cycle 1

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    End point title
    		 QTcF (QT Interval Corrected for Heart Rate Using Fridericia's Formula) Change from Baseline at Cycle 1 [22]
    End point description
    ECG Measurements: QTcF (QT Interval (interval from the beginning of the QRS complex to the end of the T wave) changes from baseline at each time point: The QTcF post baseline measurement obtained at time t minus baseline QTcF measurement. Treated Set-Phase I part: Treated Set was defined as all patients who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason. Only participants with non-missing values are reported. The 350 mg + LDAC arm of phase I and II were combined into one arm to provide maximum information on QT changes and presented together with the Phase I schedule B 450 mg arm, as pre specified in the study protocol.
    End point type
    Secondary
    End point timeframe
    Baseline (Days -14 to -1) and day 1 (1 hour and 24 hours) after start of infusion.
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified in the protocol only arms with sufficient subject numbers were included in this endpoint.
    End point values
    		 Phase I Schedule B. Volasertib 450 mg Phase I+II Volasertib 350 mg+LDAC
    Number of subjects analysed
    23
    50
    Units: millisecond (ms)
    arithmetic mean (standard deviation)
        Change from baseline after 1 hour
    29.6 ( 8.1 )
    18.5 ( 10.4 )
        Change from baseline after 24 hour
    -0.5 ( 9.8 )
    1.9 ( 10.5 )
    No statistical analyses for this end point

    Secondary: Phase I Schedule A: Incidence and Intensity of Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), based on the number of patients with AEs with CTCAE Grade ≥3 during Cycle 1

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    End point title
    		 Phase I Schedule A: Incidence and Intensity of Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), based on the number of patients with AEs with CTCAE Grade ≥3 during Cycle 1 [23]
    End point description
    Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported. Treated set-Phase I part: Treated set was defined as all patients in Phase I who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason.
    End point type
    Secondary
    End point timeframe
    First treatment cycle, up to 28 days.
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint only considers the Phase IA arms, other arms are reported in a separate endpoint.
    End point values
    		 Phase I Schedule A. Volasertib 150 mg+LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule A. Volasertib+LDAC
    Number of subjects analysed
    4
    3
    5
    9
    8
    3
    32
    Units: Participants
        Grade 3
    0
    0
    1
    1
    2
    1
    5
        Grade 4
    2
    3
    3
    5
    3
    1
    17
        Grade 5
    0
    0
    0
    3
    2
    1
    6
    No statistical analyses for this end point

    Secondary: Phase I Schedule B: Incidence and Intensity of Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), based on the number of patients with AEs with CTCAE Grade ≥3 during Cycle 1

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    End point title
    		 Phase I Schedule B: Incidence and Intensity of Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), based on the number of patients with AEs with CTCAE Grade ≥3 during Cycle 1 [24]
    End point description
    Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported. Treated set-Phase I part: Treated set was defined as all patients in Phase I who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason.
    End point type
    Secondary
    End point timeframe
    First treatment cycle, up to 28 days.
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint only considers the Phase IB arms, other arms are reported in a separate endpoint.
    End point values
    		 Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 550 mg Phase I Schedule B. Volasertib
    Number of subjects analysed
    11
    2
    5
    6
    23
    5
    4
    56
    Units: Participants
        Grade 3
    5
    0
    1
    0
    5
    0
    0
    11
        Grade 4
    4
    1
    3
    4
    14
    1
    3
    30
        Grade 5
    1
    1
    0
    0
    2
    1
    1
    6
    No statistical analyses for this end point

    Secondary: Phase I Schedule A: Incidence and Intensity of Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), based on the number of patients with AEs with CTCAE Grade ≥3 during all cycles

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    End point title
    		 Phase I Schedule A: Incidence and Intensity of Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), based on the number of patients with AEs with CTCAE Grade ≥3 during all cycles [25]
    End point description
    Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported. Treated set-Phase I part: Treated set was defined as all patients in Phase I who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason.
    End point type
    Secondary
    End point timeframe
    From first drug administration until 21 days after the last trial drug administration in the last treatment cycle, up to 615 days.
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint only considers the Phase IA arms, other arms are reported in a separate endpoint.
    End point values
    		 Phase I Schedule A. Volasertib 150 mg+LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule A. Volasertib+LDAC
    Number of subjects analysed
    4
    3
    5
    9
    8
    3
    32
    Units: Participants
        Grade 3
    1
    0
    0
    1
    2
    1
    5
        Grade 4
    1
    3
    5
    5
    3
    1
    18
        Grade 5
    1
    0
    0
    3
    2
    1
    7
    No statistical analyses for this end point

    Secondary: Phase I Schedule B: Incidence and Intensity of Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), based on the number of patients with AEs with CTCAE Grade ≥3 during all cycles

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    End point title
    		 Phase I Schedule B: Incidence and Intensity of Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), based on the number of patients with AEs with CTCAE Grade ≥3 during all cycles [26]
    End point description
    Number of patients with AEs following in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported. Treated set-Phase I part: the treated set was defined as all patients in Phase I who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason.
    End point type
    Secondary
    End point timeframe
    From first drug administration until 21 days after the last trial drug administration in the last treatment cycle, up to 597 days.
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint only considers the Phase IB arms, other arms are reported in a separate endpoint.
    End point values
    		 Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 550 mg Phase I Schedule B. Volasertib
    Number of subjects analysed
    11
    2
    5
    6
    23
    5
    4
    56
    Units: Participants
        Grade 3
    5
    0
    1
    0
    3
    0
    0
    9
        Grade 4
    4
    1
    3
    5
    15
    1
    3
    32
        Grade 5
    2
    1
    0
    0
    3
    2
    1
    9
    No statistical analyses for this end point

    Secondary: Phase II: Incidence and Intensity of Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), based on the number of patients with AEs with CTCAE Grade ≥3 during all cycles

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    End point title
    		 Phase II: Incidence and Intensity of Adverse Events (AEs) Graded According to Common Terminology Criteria for Adverse Events (CTCAE), based on the number of patients with AEs with CTCAE Grade ≥3 during all cycles [27]
    End point description
    Number of patients with AEs following in the in the categories 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related AE) of CTCAE is reported. Treated set-Phase II part: the treated set (Phase II) was defined as all patients in Phase II who received at least a single dose of either Volasertib or LDAC.
    End point type
    Secondary
    End point timeframe
    From first drug administration until 21 days after the last trial drug administration in the last treatment cycle, up to 890 days.
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint only considers the Phase II arms, other arms are reported in a separate endpoint.
    End point values
    		 Phase II Schedule C. LDAC Phase II Schedule A. Volasertib 350 mg+LDAC
    Number of subjects analysed
    45
    42
    Units: Participants
        Grade 3
    13
    12
        Grade 4
    13
    20
        Grade 5
    6
    8
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first drug administration until 21 days after the last trial drug administration in the last treatment cycle, up to 3325 days.
    Adverse event reporting additional description
    Treated Set-phase I part: patients who received at least a single dose of either Volasertib or LDAC, including patients who were replaced for any reason. Phase I: all patients who received at least a single dose of either Volasertib or LDAC.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Phase I Schedule A. Volasertib 150 mg+LDAC
    Reporting group description
    		 Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase II Schedule C. LDAC
    Reporting group description
    		 Low-dose cytarabine (LDAC) monotherapy 2x20 milligram (mg) per day administered by subcutaneous injection on days 1-10 of each 28 days treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 200 mg+LDAC
    Reporting group description
    		 Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 250 mg+LDAC
    Reporting group description
    		 Volasertib 250 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 300 mg+LDAC
    Reporting group description
    		 Volasertib 300 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase II Schedule A. Volasertib 350 mg+LDAC
    Reporting group description
    		 Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 350 mg+LDAC
    Reporting group description
    		 Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule A. Volasertib 400 mg+LDAC
    Reporting group description
    		 Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle) and Low-dose cytarabine (LDAC) 2x20mg per day administered by subcutaneous injection on days 1-10 of each 28 day treatment cycle.

    Reporting group title
    Phase I Schedule B. Volasertib 400 mg
    Reporting group description
    		 Volasertib 400 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 350 mg
    Reporting group description
    		 Volasertib 350 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 150 mg
    Reporting group description
    		 Volasertib 150 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 200 mg
    Reporting group description
    		 Volasertib 200 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 500 mg
    Reporting group description
    		 Volasertib 500 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 450 mg
    Reporting group description
    		 Volasertib 450 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Reporting group title
    Phase I Schedule B. Volasertib 550 mg
    Reporting group description
    		 Volasertib 550 milligram (mg) administered by Intravenous Infusion (IV) over 60 minutes on Days 1 and 15 (28-day cycle).

    Serious adverse events
    		 Phase I Schedule A. Volasertib 150 mg+LDAC Phase II Schedule C. LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase II Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 550 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 4 (50.00%)
    29 / 45 (64.44%)
    3 / 3 (100.00%)
    3 / 5 (60.00%)
    7 / 9 (77.78%)
    34 / 42 (80.95%)
    6 / 8 (75.00%)
    3 / 3 (100.00%)
    3 / 6 (50.00%)
    3 / 5 (60.00%)
    7 / 11 (63.64%)
    1 / 2 (50.00%)
    3 / 5 (60.00%)
    16 / 23 (69.57%)
    3 / 4 (75.00%)
         number of deaths (all causes)
    4
    45
    3
    4
    9
    38
    8
    3
    6
    3
    11
    2
    5
    21
    4
         number of deaths resulting from adverse events
    0
    0
    0
    0
    1
    6
    0
    0
    0
    0
    1
    0
    1
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Central nervous system leukaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Catheterisation venous
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 4 (0.00%)
    5 / 45 (11.11%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    2 / 9 (22.22%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 6
    0 / 1
    0 / 1
    0 / 2
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypothermia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    2 / 4 (50.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 4 (0.00%)
    8 / 45 (17.78%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    5 / 42 (11.90%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 8
    0 / 0
    0 / 1
    0 / 0
    3 / 5
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperventilation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infiltration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Pulmonary oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Acute psychosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Brain natriuretic peptide increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    3 / 5 (60.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 5
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Meniscus injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Long QT syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuralgia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    5 / 42 (11.90%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    4 / 5
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    2 / 4 (50.00%)
    6 / 45 (13.33%)
    2 / 3 (66.67%)
    2 / 5 (40.00%)
    2 / 9 (22.22%)
    23 / 42 (54.76%)
    3 / 8 (37.50%)
    2 / 3 (66.67%)
    2 / 6 (33.33%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    2 / 5 (40.00%)
    9 / 23 (39.13%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 3
    5 / 9
    2 / 2
    0 / 3
    0 / 2
    22 / 27
    0 / 4
    1 / 2
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 15
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    5 / 42 (11.90%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 4
    0 / 0
    0 / 0
    0 / 0
    5 / 5
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    2 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea haemorrhagic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mouth ulceration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tongue haematoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis allergic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephropathy
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Crystal arthropathy
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polyarthritis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspergillus infection
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial pyelonephritis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral fungal infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    8 / 42 (19.05%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    3 / 11 (27.27%)
    0 / 2 (0.00%)
    2 / 5 (40.00%)
    4 / 23 (17.39%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    1 / 1
    3 / 11
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 3
    0 / 0
    1 / 2
    0 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    1 / 1
    1 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 2
    1 / 1
    Pneumonia fungal
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 2
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mycosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    2 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stenotrophomonas infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Klebsiella sepsis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Phase I Schedule A. Volasertib 150 mg+LDAC Phase II Schedule C. LDAC Phase I Schedule A. Volasertib 200 mg+LDAC Phase I Schedule A. Volasertib 250 mg+LDAC Phase I Schedule A. Volasertib 300 mg+LDAC Phase II Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 350 mg+LDAC Phase I Schedule A. Volasertib 400 mg+LDAC Phase I Schedule B. Volasertib 400 mg Phase I Schedule B. Volasertib 350 mg Phase I Schedule B. Volasertib 150 mg Phase I Schedule B. Volasertib 200 mg Phase I Schedule B. Volasertib 500 mg Phase I Schedule B. Volasertib 450 mg Phase I Schedule B. Volasertib 550 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    43 / 45 (95.56%)
    3 / 3 (100.00%)
    5 / 5 (100.00%)
    9 / 9 (100.00%)
    41 / 42 (97.62%)
    8 / 8 (100.00%)
    3 / 3 (100.00%)
    6 / 6 (100.00%)
    5 / 5 (100.00%)
    11 / 11 (100.00%)
    2 / 2 (100.00%)
    5 / 5 (100.00%)
    23 / 23 (100.00%)
    4 / 4 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Chloroma
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    2 / 9 (22.22%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    2
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Leukaemia cutis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Meningioma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasm progression
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Small intestine carcinoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    Angiopathy
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Circulatory collapse
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Haematoma
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    1 / 9 (11.11%)
    2 / 42 (4.76%)
    3 / 8 (37.50%)
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    1 / 2 (50.00%)
    2 / 5 (40.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    2
    1
    2
    3
    0
    4
    0
    2
    1
    2
    3
    0
    Haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Hypertension
         subjects affected / exposed
    1 / 4 (25.00%)
    4 / 45 (8.89%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    5 / 23 (21.74%)
    2 / 4 (50.00%)
         occurrences all number
    1
    4
    0
    1
    0
    2
    0
    0
    1
    0
    1
    0
    1
    5
    3
    Hypertensive crisis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    7 / 42 (16.67%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    1
    0
    1
    7
    1
    1
    0
    0
    0
    0
    0
    1
    0
    Infarction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Peripheral coldness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Peripheral embolism
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Thrombophlebitis
         subjects affected / exposed
    0 / 4 (0.00%)
    4 / 45 (8.89%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    2
    0
    Varicose vein
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Lymphoedema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Phlebitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Surgical and medical procedures
    Central venous catheterisation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nail operation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Asthenia
         subjects affected / exposed
    0 / 4 (0.00%)
    11 / 45 (24.44%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    10 / 42 (23.81%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    16
    0
    1
    1
    15
    0
    1
    0
    0
    1
    0
    0
    0
    0
    Calcinosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Catheter site erythema
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Catheter site oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Chest discomfort
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    Chest pain
         subjects affected / exposed
    0 / 4 (0.00%)
    3 / 45 (6.67%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    2 / 9 (22.22%)
    4 / 42 (9.52%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    4
    3
    0
    2
    4
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Chills
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    1 / 9 (11.11%)
    2 / 42 (4.76%)
    3 / 8 (37.50%)
    2 / 3 (66.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    2 / 5 (40.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    2
    1
    2
    3
    2
    0
    1
    1
    0
    2
    1
    0
    Fatigue
         subjects affected / exposed
    1 / 4 (25.00%)
    11 / 45 (24.44%)
    1 / 3 (33.33%)
    5 / 5 (100.00%)
    5 / 9 (55.56%)
    11 / 42 (26.19%)
    4 / 8 (50.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    3 / 11 (27.27%)
    2 / 2 (100.00%)
    2 / 5 (40.00%)
    4 / 23 (17.39%)
    2 / 4 (50.00%)
         occurrences all number
    1
    14
    1
    10
    6
    11
    5
    1
    0
    1
    3
    2
    2
    5
    2
    Feeling cold
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Feeling hot
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Feeling of body temperature change
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Gait disturbance
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    General physical health deterioration
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    1 / 9 (11.11%)
    5 / 42 (11.90%)
    3 / 8 (37.50%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    13 / 23 (56.52%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    1
    3
    1
    6
    6
    1
    2
    1
    1
    0
    1
    13
    0
    Granuloma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Induration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Inflammation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    2
    0
    Influenza like illness
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Infusion site pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site haematoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    3 / 42 (7.14%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    3
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Local swelling
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    Localised oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Malaise
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Mucosal inflammation
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    2 / 9 (22.22%)
    10 / 42 (23.81%)
    3 / 8 (37.50%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    1
    2
    12
    3
    0
    2
    1
    1
    0
    0
    2
    0
    Oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    2 / 42 (4.76%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    1 / 4 (25.00%)
         occurrences all number
    0
    2
    1
    0
    1
    2
    1
    1
    0
    0
    1
    0
    0
    4
    1
    Oedema mucosal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 4 (0.00%)
    9 / 45 (20.00%)
    2 / 3 (66.67%)
    1 / 5 (20.00%)
    5 / 9 (55.56%)
    12 / 42 (28.57%)
    2 / 8 (25.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    2 / 11 (18.18%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    9 / 23 (39.13%)
    0 / 4 (0.00%)
         occurrences all number
    0
    11
    3
    1
    8
    16
    5
    1
    1
    1
    2
    1
    0
    9
    0
    Pain
         subjects affected / exposed
    1 / 4 (25.00%)
    3 / 45 (6.67%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    5 / 42 (11.90%)
    3 / 8 (37.50%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    3 / 11 (27.27%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    1
    3
    0
    0
    2
    5
    3
    1
    1
    1
    3
    0
    0
    3
    0
    Puncture site pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 4 (0.00%)
    8 / 45 (17.78%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    4 / 9 (44.44%)
    13 / 42 (30.95%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    11
    1
    1
    10
    18
    1
    0
    0
    0
    3
    0
    0
    2
    0
    Thirst decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Peripheral swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    2 / 9 (22.22%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    4
    2
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Catheter site pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Hyperthermia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Discomfort
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Mucosal haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    4
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Social circumstances
    Fasting
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    Breast enlargement
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Genital swelling
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Haematospermia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Nipple disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Pelvic pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Penile oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Scrotal oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Vulvovaginal erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Genital burning sensation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Bronchial secretion retention
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dysphonia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    1
    1
    0
    0
    0
    0
    1
    1
    0
    0
    1
    0
    Cough
         subjects affected / exposed
    0 / 4 (0.00%)
    6 / 45 (13.33%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    4 / 9 (44.44%)
    10 / 42 (23.81%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    6 / 23 (26.09%)
    0 / 4 (0.00%)
         occurrences all number
    0
    8
    1
    2
    4
    18
    2
    0
    1
    0
    2
    0
    1
    10
    0
    Dyspnoea
         subjects affected / exposed
    0 / 4 (0.00%)
    8 / 45 (17.78%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    4 / 9 (44.44%)
    10 / 42 (23.81%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    4 / 23 (17.39%)
    0 / 4 (0.00%)
         occurrences all number
    0
    10
    1
    0
    5
    12
    2
    0
    2
    0
    1
    0
    1
    4
    0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    3 / 5 (60.00%)
    2 / 9 (22.22%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    4
    2
    0
    1
    0
    1
    1
    1
    0
    0
    1
    0
    Haemoptysis
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    5 / 42 (11.90%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    1 / 4 (25.00%)
         occurrences all number
    1
    1
    0
    0
    2
    6
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Epistaxis
         subjects affected / exposed
    0 / 4 (0.00%)
    9 / 45 (20.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    3 / 9 (33.33%)
    16 / 42 (38.10%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    2 / 11 (18.18%)
    1 / 2 (50.00%)
    2 / 5 (40.00%)
    5 / 23 (21.74%)
    1 / 4 (25.00%)
         occurrences all number
    0
    11
    0
    1
    7
    24
    2
    0
    5
    2
    2
    2
    2
    6
    1
    Hiccups
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Laryngeal disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Lung infiltration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    2 / 9 (22.22%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    1
    1
    0
    0
    0
    0
    2
    0
    Lung disorder
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nasal inflammation
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    5 / 42 (11.90%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    5
    1
    1
    0
    0
    0
    0
    1
    3
    0
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Pleural effusion
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    4 / 9 (44.44%)
    3 / 42 (7.14%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    2
    4
    3
    1
    0
    0
    0
    2
    0
    1
    2
    0
    Productive cough
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    0
    0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Respiratory failure
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Sputum discoloured
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Sputum retention
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Vocal cord disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Rales
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Rhonchi
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Throat irritation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Anxiety
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    5 / 42 (11.90%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    1
    1
    5
    1
    0
    1
    0
    1
    0
    1
    1
    0
    Communication disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Confusional state
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    1 / 4 (25.00%)
         occurrences all number
    0
    2
    0
    1
    1
    2
    0
    0
    0
    0
    0
    0
    0
    2
    1
    Depressed mood
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Depression
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Disorientation
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Hallucination
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Hallucination, visual
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Initial insomnia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 4 (0.00%)
    4 / 45 (8.89%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    3
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Panic attack
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Restlessness
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    1
    0
    1
    0
    0
    0
    0
    0
    1
    Sleep disorder
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    1 / 4 (25.00%)
         occurrences all number
    1
    3
    1
    0
    0
    3
    0
    0
    0
    0
    2
    0
    0
    1
    1
    Suicidal ideation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    2
    0
    0
    5
    1
    Activated partial thromboplastin time shortened
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    3 / 3 (100.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    4 / 23 (17.39%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    4
    2
    0
    0
    0
    0
    1
    0
    2
    0
    1
    4
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    2 / 3 (66.67%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    1 / 2 (50.00%)
    1 / 5 (20.00%)
    5 / 23 (21.74%)
    0 / 4 (0.00%)
         occurrences all number
    0
    3
    2
    1
    0
    0
    0
    0
    1
    0
    1
    1
    1
    7
    0
    Blast cell count increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Blood albumin decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood albumin increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    3 / 11 (27.27%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    3
    0
    0
    0
    0
    6
    0
    0
    3
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    2 / 3 (66.67%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    0
    0
    2
    0
    2
    0
    0
    7
    0
    Blood chloride increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Blood creatine phosphokinase decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood creatinine
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood creatinine decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    2 / 9 (22.22%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 4 (25.00%)
    3 / 45 (6.67%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    3 / 9 (33.33%)
    2 / 42 (4.76%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    2 / 11 (18.18%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    6 / 23 (26.09%)
    2 / 4 (50.00%)
         occurrences all number
    1
    3
    0
    3
    4
    2
    1
    0
    2
    2
    3
    1
    0
    12
    2
    Blood fibrinogen increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Blood glucose increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    4
    0
    Blood iron decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood iron increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood lactate dehydrogenase decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    4 / 11 (36.36%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    4
    0
    0
    5
    0
    Blood phosphorus decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Blood potassium decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    2
    0
    0
    3
    0
    0
    0
    0
    1
    0
    Blood pressure increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    2
    0
    0
    0
    1
    0
    0
    0
    0
    Blood triglycerides increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood urea decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood urea increased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    2 / 9 (22.22%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    3 / 11 (27.27%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    3
    0
    2
    2
    0
    0
    0
    5
    1
    3
    1
    0
    0
    0
    Blood uric acid increased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    0
    1
    1
    0
    0
    0
    3
    0
    1
    1
    0
    4
    2
    Blood urine present
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Body temperature increased
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    1
    2
    0
    1
    0
    0
    0
    0
    0
    0
    2
    0
    0
    1
    0
    Breath sounds abnormal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    2 / 4 (50.00%)
    5 / 45 (11.11%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    4 / 9 (44.44%)
    2 / 42 (4.76%)
    4 / 8 (50.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    1 / 5 (20.00%)
    4 / 11 (36.36%)
    2 / 2 (100.00%)
    1 / 5 (20.00%)
    7 / 23 (30.43%)
    3 / 4 (75.00%)
         occurrences all number
    2
    6
    1
    3
    4
    2
    4
    1
    3
    1
    4
    2
    1
    8
    3
    Candida test positive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    5 / 23 (21.74%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    2
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    14
    1
    Electrocardiogram change
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Enterococcus test positive
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Escherichia test positive
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    2 / 3 (66.67%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    4 / 11 (36.36%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    2
    1
    1
    1
    0
    0
    0
    1
    4
    0
    0
    3
    0
    Heart rate increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Liver function test abnormal
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Prostatic specific antigen increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Protein total decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    3 / 11 (27.27%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    2
    0
    Prothrombin time prolonged
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    Serum ferritin increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Thrombin time shortened
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Troponin T increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    5
    0
    Troponin increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    1
    1
    0
    1
    3
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Weight increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    1
    1
    0
    0
    0
    1
    1
    0
    0
    0
    White blood cells urine
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Allergic transfusion reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    1
    0
    Drug administration error
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Excoriation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Fall
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    4 / 9 (44.44%)
    4 / 42 (9.52%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    4 / 23 (17.39%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    2
    4
    4
    1
    1
    1
    0
    0
    0
    1
    4
    0
    Laceration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Lip injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Procedural pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Transfusion reaction
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    2
    0
    Wound
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Skin abrasion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Stoma site haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Aortic valve incompetence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Atrioventricular block
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Bradycardia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    2
    0
    Bundle branch block right
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    2
    0
    Cardiac arrest
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Cardiac disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cardiac failure
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    3
    0
    0
    1
    0
    1
    0
    0
    0
    0
    Cardiac valve disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cardiomegaly
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Cardiomyopathy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cardiovascular disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Congestive cardiomyopathy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Extrasystoles
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    Heart valve incompetence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypertensive heart disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Left ventricular hypertrophy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    2
    0
    0
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 4 (0.00%)
    4 / 45 (8.89%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Pericardial effusion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    2 / 9 (22.22%)
    0 / 42 (0.00%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    2
    0
    1
    0
    0
    0
    0
    1
    0
    Tachyarrhythmia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    2
    0
    0
    0
    0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Arrhythmia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Nervous system disorders
    Burning sensation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 45 (4.44%)
    1 / 3 (33.33%)
    4 / 5 (80.00%)
    2 / 9 (22.22%)
    3 / 42 (7.14%)
    2 / 8 (25.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    4 / 23 (17.39%)
    1 / 4 (25.00%)
         occurrences all number
    1
    2
    1
    4
    2
    6
    3
    1
    0
    0
    1
    0
    0
    4
    1
    Headache
         subjects affected / exposed
    1 / 4 (25.00%)
    7 / 45 (15.56%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    4 / 42 (9.52%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    2 / 5 (40.00%)
    5 / 23 (21.74%)
    1 / 4 (25.00%)
         occurrences all number
    2
    9
    0
    0
    0
    6
    1
    1
    2
    3
    1
    0
    3
    6
    1
    Hemiparesis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Orthostatic intolerance
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    0 / 4 (0.00%)
    3 / 45 (6.67%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Polyneuropathy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Sinus headache
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Syncope
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Tremor
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    2
    0
    1
    0
    0
    0
    0
    0
    1
    Ageusia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Dysgeusia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Hypotonia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 4 (25.00%)
    12 / 45 (26.67%)
    2 / 3 (66.67%)
    4 / 5 (80.00%)
    6 / 9 (66.67%)
    14 / 42 (33.33%)
    3 / 8 (37.50%)
    1 / 3 (33.33%)
    4 / 6 (66.67%)
    5 / 5 (100.00%)
    4 / 11 (36.36%)
    2 / 2 (100.00%)
    1 / 5 (20.00%)
    11 / 23 (47.83%)
    2 / 4 (50.00%)
         occurrences all number
    1
    31
    3
    5
    20
    27
    6
    1
    6
    6
    4
    2
    3
    16
    2
    Febrile neutropenia
         subjects affected / exposed
    0 / 4 (0.00%)
    4 / 45 (8.89%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    8 / 42 (19.05%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    4 / 23 (17.39%)
    1 / 4 (25.00%)
         occurrences all number
    0
    6
    0
    0
    2
    9
    0
    0
    0
    1
    1
    0
    0
    4
    1
    Leukocytosis
         subjects affected / exposed
    0 / 4 (0.00%)
    3 / 45 (6.67%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    4 / 11 (36.36%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    6
    0
    1
    1
    0
    0
    0
    0
    0
    5
    0
    0
    1
    0
    Leukopenia
         subjects affected / exposed
    1 / 4 (25.00%)
    3 / 45 (6.67%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    5 / 9 (55.56%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    2 / 11 (18.18%)
    1 / 2 (50.00%)
    1 / 5 (20.00%)
    7 / 23 (30.43%)
    1 / 4 (25.00%)
         occurrences all number
    1
    7
    2
    3
    9
    1
    2
    1
    2
    2
    3
    1
    1
    10
    1
    Lymphadenopathy
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    0
    0
    0
    0
    1
    1
    0
    2
    0
    Neutropenia
         subjects affected / exposed
    0 / 4 (0.00%)
    5 / 45 (11.11%)
    2 / 3 (66.67%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    11 / 42 (26.19%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    1 / 5 (20.00%)
    2 / 11 (18.18%)
    1 / 2 (50.00%)
    1 / 5 (20.00%)
    12 / 23 (52.17%)
    1 / 4 (25.00%)
         occurrences all number
    0
    10
    2
    1
    1
    36
    0
    0
    5
    1
    3
    1
    1
    16
    1
    Splenomegaly
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    2 / 9 (22.22%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    1
    1
    0
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    8 / 45 (17.78%)
    2 / 3 (66.67%)
    4 / 5 (80.00%)
    5 / 9 (55.56%)
    9 / 42 (21.43%)
    3 / 8 (37.50%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    3 / 5 (60.00%)
    5 / 11 (45.45%)
    1 / 2 (50.00%)
    1 / 5 (20.00%)
    12 / 23 (52.17%)
    2 / 4 (50.00%)
         occurrences all number
    0
    26
    2
    5
    16
    45
    9
    1
    5
    3
    5
    1
    1
    22
    2
    Cytopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Ear and labyrinth disorders
    Ear haemorrhage
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    2 / 9 (22.22%)
    3 / 42 (7.14%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    2
    3
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Dry eye
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Erythema of eyelid
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Eye haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    1
    0
    0
    0
    0
    0
    2
    0
    Eyelid oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    Glaucoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Macular degeneration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Visual acuity reduced
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Visual impairment
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    2
    0
    0
    0
    0
    0
    Hyphaema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Photopsia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    4 / 45 (8.89%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    2 / 9 (22.22%)
    4 / 42 (9.52%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    4 / 23 (17.39%)
    0 / 4 (0.00%)
         occurrences all number
    0
    6
    0
    2
    3
    4
    1
    0
    0
    1
    0
    0
    0
    4
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 4 (25.00%)
    4 / 45 (8.89%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    3 / 42 (7.14%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    1
    4
    1
    0
    1
    4
    1
    0
    1
    0
    0
    0
    0
    2
    0
    Abnormal faeces
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Anal haemorrhage
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Ascites
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 4 (0.00%)
    12 / 45 (26.67%)
    3 / 3 (100.00%)
    2 / 5 (40.00%)
    2 / 9 (22.22%)
    18 / 42 (42.86%)
    3 / 8 (37.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    3 / 11 (27.27%)
    1 / 2 (50.00%)
    1 / 5 (20.00%)
    6 / 23 (26.09%)
    2 / 4 (50.00%)
         occurrences all number
    0
    14
    4
    3
    2
    26
    3
    0
    1
    0
    4
    1
    1
    7
    2
    Diarrhoea
         subjects affected / exposed
    2 / 4 (50.00%)
    11 / 45 (24.44%)
    2 / 3 (66.67%)
    2 / 5 (40.00%)
    4 / 9 (44.44%)
    13 / 42 (30.95%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    2 / 5 (40.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    2 / 5 (40.00%)
    6 / 23 (26.09%)
    0 / 4 (0.00%)
         occurrences all number
    2
    14
    4
    7
    7
    21
    1
    0
    5
    3
    1
    0
    2
    8
    0
    Dry mouth
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    2 / 3 (66.67%)
    0 / 5 (0.00%)
    2 / 9 (22.22%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    2
    0
    2
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dysphagia
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    2 / 3 (66.67%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    3 / 42 (7.14%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    2
    0
    1
    3
    1
    0
    1
    0
    0
    0
    1
    0
    0
    Enterocolitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Faecaloma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Flatulence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    4 / 8 (50.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    4
    0
    1
    0
    0
    0
    1
    1
    0
    Gastritis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Gingival bleeding
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    1
    2
    1
    0
    0
    3
    0
    0
    0
    0
    1
    0
    Gingival discolouration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gingival pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gingival swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Glossodynia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Haematochezia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Haemorrhoids
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    2 / 5 (40.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    2
    0
    0
    Hiatus hernia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Mouth haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    3 / 45 (6.67%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    1 / 4 (25.00%)
         occurrences all number
    0
    3
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    3
    1
    Mouth ulceration
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    2 / 4 (50.00%)
    16 / 45 (35.56%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    4 / 9 (44.44%)
    19 / 42 (45.24%)
    4 / 8 (50.00%)
    2 / 3 (66.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    0 / 2 (0.00%)
    2 / 5 (40.00%)
    7 / 23 (30.43%)
    2 / 4 (50.00%)
         occurrences all number
    2
    22
    0
    5
    6
    28
    6
    2
    2
    0
    2
    0
    3
    14
    2
    Oesophagitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Oral mucosal erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Oral pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    1
    0
    0
    1
    0
    0
    0
    1
    0
    Periodontal disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Proctalgia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    1
    0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Small intestine ulcer
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    3 / 5 (60.00%)
    5 / 23 (21.74%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    3
    0
    0
    0
    0
    1
    0
    3
    5
    0
    Tongue coated
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Tongue ulceration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Toothache
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    2 / 4 (50.00%)
    6 / 45 (13.33%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    4 / 9 (44.44%)
    16 / 42 (38.10%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    1 / 2 (50.00%)
    1 / 5 (20.00%)
    6 / 23 (26.09%)
    1 / 4 (25.00%)
         occurrences all number
    2
    7
    1
    2
    5
    30
    0
    1
    0
    0
    1
    1
    1
    8
    1
    Anal incontinence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    2
    0
    0
    0
    0
    0
    0
    1
    0
    Aphthous ulcer
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    4
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Tongue discolouration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Abdominal discomfort
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Gastric ulcer
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Palatal disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Tongue haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hepatic congestion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Hepatic cyst
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hepatic lesion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hepatomegaly
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    4
    1
    Hepatic steatosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    2 / 8 (25.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    2 / 4 (50.00%)
         occurrences all number
    0
    0
    0
    1
    0
    5
    2
    1
    3
    1
    0
    0
    0
    3
    2
    Blister
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood blister
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    2 / 2 (100.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    1
    0
    1
    2
    0
    0
    0
    Dermatitis atopic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dermatitis exfoliative
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 4 (0.00%)
    3 / 45 (6.67%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    3 / 9 (33.33%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    3
    0
    0
    3
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    2
    1
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    Haemorrhage subcutaneous
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    3 / 42 (7.14%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    0
    1
    3
    1
    1
    0
    0
    2
    0
    0
    0
    0
    Night sweats
         subjects affected / exposed
    0 / 4 (0.00%)
    3 / 45 (6.67%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    4 / 42 (9.52%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    1 / 4 (25.00%)
         occurrences all number
    0
    3
    1
    1
    0
    5
    0
    1
    4
    1
    1
    0
    0
    3
    1
    Pain of skin
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Parapsoriasis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Petechiae
         subjects affected / exposed
    0 / 4 (0.00%)
    5 / 45 (11.11%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    2 / 9 (22.22%)
    10 / 42 (23.81%)
    2 / 8 (25.00%)
    2 / 3 (66.67%)
    4 / 6 (66.67%)
    1 / 5 (20.00%)
    4 / 11 (36.36%)
    0 / 2 (0.00%)
    2 / 5 (40.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    8
    0
    4
    2
    12
    2
    2
    4
    1
    4
    0
    2
    3
    0
    Pruritus
         subjects affected / exposed
    0 / 4 (0.00%)
    7 / 45 (15.56%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    4 / 42 (9.52%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    1 / 4 (25.00%)
         occurrences all number
    0
    8
    0
    0
    0
    5
    1
    0
    2
    0
    0
    0
    0
    2
    1
    Psoriasis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Purpura
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Rash
         subjects affected / exposed
    0 / 4 (0.00%)
    4 / 45 (8.89%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    1 / 5 (20.00%)
    2 / 11 (18.18%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    4 / 23 (17.39%)
    0 / 4 (0.00%)
         occurrences all number
    0
    4
    0
    1
    0
    3
    1
    0
    3
    1
    2
    1
    0
    5
    0
    Skin erosion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Skin haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Skin lesion
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    2 / 42 (4.76%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    1
    2
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Swelling face
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Eczema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Ingrowing nail
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Intertrigo
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Renal and urinary disorders
    Anuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Bladder pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dysuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    3 / 42 (7.14%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    3
    0
    1
    0
    0
    0
    0
    0
    3
    0
    Glycosuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Haematuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    2 / 3 (66.67%)
    2 / 5 (40.00%)
    2 / 9 (22.22%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    3
    2
    2
    1
    0
    0
    0
    0
    1
    0
    0
    1
    0
    Leukocyturia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Micturition disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Nephropathy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Nocturia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Pollakiuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Renal atrophy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Renal cyst
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Renal impairment
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Renal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Urethral haemorrhage
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Urethral pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Urinary incontinence
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    2
    1
    1
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Urinary retention
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    2
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Chronic kidney disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Incontinence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Micturition urgency
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Endocrine disorders
    Adrenal disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 4 (0.00%)
    4 / 45 (8.89%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    3 / 9 (33.33%)
    7 / 42 (16.67%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    3 / 5 (60.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    5
    1
    0
    3
    9
    3
    0
    0
    1
    0
    0
    3
    4
    0
    Arthritis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    0
    0
    0
    4
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Back pain
         subjects affected / exposed
    2 / 4 (50.00%)
    10 / 45 (22.22%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    2 / 9 (22.22%)
    6 / 42 (14.29%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    1 / 4 (25.00%)
         occurrences all number
    2
    10
    1
    1
    2
    6
    0
    0
    1
    0
    1
    0
    0
    3
    3
    Bone lesion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Bone pain
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    2
    0
    0
    3
    0
    1
    0
    0
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Groin pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Joint swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 4 (0.00%)
    3 / 45 (6.67%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    3
    1
    2
    0
    3
    1
    0
    2
    0
    0
    0
    0
    1
    0
    Muscular weakness
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    1
    2
    1
    1
    0
    0
    0
    0
    0
    0
    3
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    2 / 3 (66.67%)
    2 / 5 (40.00%)
    1 / 9 (11.11%)
    2 / 42 (4.76%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    2
    2
    1
    2
    1
    0
    0
    0
    0
    0
    1
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 45 (4.44%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    3
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Myopathy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Osteoarthritis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Osteolysis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Osteopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Osteoporosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 4 (0.00%)
    6 / 45 (13.33%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    3 / 9 (33.33%)
    3 / 42 (7.14%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    1 / 4 (25.00%)
         occurrences all number
    0
    7
    0
    3
    4
    7
    0
    0
    1
    0
    1
    0
    0
    3
    1
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    1
    0
    0
    1
    0
    Infections and infestations
    Bacterial infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Beta haemolytic streptococcal infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    3
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Candida infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    0
    0
    0
    0
    1
    1
    0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cystitis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Device related infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    Diverticulitis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Enterococcal infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Erysipelas
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Escherichia infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Fungal infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Fungal skin infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Fusobacterium infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Gingivitis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Herpes simplex
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Herpes virus infection
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    1
    1
    0
    Herpes zoster
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Micrococcus infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Nail bed infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 45 (4.44%)
    1 / 3 (33.33%)
    2 / 5 (40.00%)
    4 / 9 (44.44%)
    0 / 42 (0.00%)
    2 / 8 (25.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    2
    1
    2
    4
    0
    2
    0
    0
    1
    1
    0
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    1 / 9 (11.11%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Oral herpes
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    0
    0
    1
    0
    1
    0
    1
    5
    0
    Pharyngitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    4
    0
    Pneumonia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    5 / 42 (11.90%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    5
    1
    0
    0
    0
    0
    0
    0
    3
    0
    Pneumonia fungal
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    1
    0
    1
    0
    0
    0
    0
    0
    Pseudomonas infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Sepsis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Staphylococcal infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Urosepsis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Osteomyelitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Post procedural infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Soft tissue infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Alkalosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    3
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Decreased appetite
         subjects affected / exposed
    2 / 4 (50.00%)
    6 / 45 (13.33%)
    2 / 3 (66.67%)
    4 / 5 (80.00%)
    5 / 9 (55.56%)
    6 / 42 (14.29%)
    2 / 8 (25.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    3 / 11 (27.27%)
    0 / 2 (0.00%)
    1 / 5 (20.00%)
    10 / 23 (43.48%)
    1 / 4 (25.00%)
         occurrences all number
    2
    6
    2
    5
    6
    10
    5
    1
    2
    1
    3
    0
    1
    14
    1
    Dehydration
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Diabetes mellitus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypercalcaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 45 (4.44%)
    2 / 3 (66.67%)
    4 / 5 (80.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    2 / 2 (100.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    0 / 4 (0.00%)
         occurrences all number
    1
    2
    3
    8
    1
    0
    0
    0
    0
    0
    2
    2
    0
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    3 / 42 (7.14%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    3
    1
    0
    6
    1
    0
    0
    1
    1
    0
    0
    0
    0
    Hypernatraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    1 / 23 (4.35%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    2
    Hyperuricaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    4 / 45 (8.89%)
    0 / 3 (0.00%)
    2 / 5 (40.00%)
    2 / 9 (22.22%)
    1 / 42 (2.38%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    3 / 23 (13.04%)
    0 / 4 (0.00%)
         occurrences all number
    0
    6
    0
    2
    4
    6
    0
    0
    0
    0
    3
    0
    0
    3
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    0 / 5 (0.00%)
    1 / 9 (11.11%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    4 / 23 (17.39%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    0
    1
    1
    0
    0
    6
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    1 / 3 (33.33%)
    3 / 5 (60.00%)
    2 / 9 (22.22%)
    2 / 42 (4.76%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    2 / 11 (18.18%)
    2 / 2 (100.00%)
    1 / 5 (20.00%)
    6 / 23 (26.09%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    1
    3
    5
    2
    1
    0
    1
    2
    2
    2
    1
    9
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    1 / 5 (20.00%)
    0 / 9 (0.00%)
    2 / 42 (4.76%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    3 / 45 (6.67%)
    1 / 3 (33.33%)
    4 / 5 (80.00%)
    4 / 9 (44.44%)
    8 / 42 (19.05%)
    6 / 8 (75.00%)
    3 / 3 (100.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 11 (18.18%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    10 / 23 (43.48%)
    2 / 4 (50.00%)
         occurrences all number
    0
    5
    1
    5
    6
    11
    6
    3
    0
    0
    3
    0
    0
    17
    4
    Hyponatraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    1 / 3 (33.33%)
    3 / 5 (60.00%)
    4 / 9 (44.44%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    1 / 4 (25.00%)
         occurrences all number
    0
    0
    1
    4
    4
    0
    0
    0
    0
    0
    1
    1
    0
    7
    1
    Hypoproteinaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    2 / 23 (8.70%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Iron overload
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 45 (2.22%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Uraemic acidosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    1 / 2 (50.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Vitamin D deficiency
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    0 / 8 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 11 (9.09%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Fluid overload
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 45 (0.00%)
    0 / 3 (0.00%)
    0 / 5 (0.00%)
    0 / 9 (0.00%)
    0 / 42 (0.00%)
    1 / 8 (12.50%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 11 (0.00%)
    0 / 2 (0.00%)
    0 / 5 (0.00%)
    0 / 23 (0.00%)
    0 / 4 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Oct 2008
    To allow for close cardiac monitoring of patients during the trial, additional Electrocardiogram (ECG) and troponin analyses were added. A formal safety analysis after the Phase I part of the trial and if necessary an updated benefit risk assessment was implemented. The Phase I part safety analysis was to be made available to all involved competent authorities and ethics committees. The blood sample for pharmacogenetic analysis was increased to 10 milliLiter (mL) to allow for different additives and different volumes in commercial tubes. The addition of further Pharmacokinetics (PK) analyses on volasertib metabolites, if applicable, was added to obtain further information on the PK of volasertib
    11 Aug 2009
    The procedure was changed for allocation of patients in the Phase I part to treatment groups. This change in allocation for the Phase I part of the trial was implemented to avoid or shorten periods with stopped recruitment. Recruitment was to be stopped if the planned number of patients at a dose level was recruited in both schedules until all patients at that dose level finished the first treatment cycle. A non-randomised allocation of patients to treatment groups reduced the risk that the planned number of patients was recruited in both schedules at the same time. Changed dose escalation in Schedule B (volasertib monotherapy) to minimise the number of patients treated at suboptimal doses of volasertib. Change in details of packaging and labelling for Low-dose cytarabine (LDAC) used in the Phase II part of the trial. Details on serious adverse event (SAE) reporting changed to enhance comprehensibility of the procedure.
    12 Nov 2009
    The procedure for allocating patients in the Phase I part to treatment schedules was changed. This change was implemented based on the first preliminary results that suggested an inferior clinical effect of volasertib monotherapy at the dose levels investigated at this point compared to the combination of volasertib and Low-dose cytarabine (LDAC). Screening for additional mutations and deregulated expression of genes was added to the planned cytogenetic and molecular genetic testing to allow the most up to date diagnostics in the trial. The sample volume of blood needed was adapted. The wording for the replacement of patients was considered misleading for the Phase II part of the trial so this was clarified. The address of the coordinating investigator was changed. The rules for pharmacodynamic investigations were changed, with the Progressive disease (PD) analysis being changed to being optional in Phase II part of the trial
    01 Dec 2010
    Details on exclusion of patients with QT interval corrected (QTc) prolongation were added to provide more accurate recommendations for the management of QTc interval prolongation and ventricular tachyarrhythmia
    26 May 2011
    Details were added on timing and preparation of the clinical trial report (CTR) at the end of the trial. An early analysis of response to therapy was added to support internal strategic decisions/planning regarding future clinical trials.
    20 Mar 2012
    Details on timing and preparation of the CTR were clarified.
    23 Jul 2013
    Details on timing and preparation of the CTR were clarified.
    14 Oct 2014
    The vial size of volasertib was changed to administer a dose of 350 milligram (mg) by the use of only 1 vial.
    12 Jan 2017
    Procedures and data collection were reduced to a minimum because the sponsor decided to discontinue volasertib development; however, patients with a clinical benefit could continue treatment. The sample size changed from about 143 to 177 enrolled (175 evaluable) to provide current and up-to-date information.
    07 Feb 2019
    Details on electronic data capture were updated.

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

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