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    Clinical Trial Results:
    A Phase Ib/II Multi-Arm Study with Venetoclax in Combination with Cobimetinib and Venetoclax in Combination with Idasanutlin in Patients with Relapsed or Refractory Acute Myeloid Leukemia Who Are Not Eligible for Cytotoxic Therapy

    Summary
    EudraCT number
    		 2015-003386-28
    Trial protocol
    		 FR   IT  
    Global end of trial date
    10 Dec 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Dec 2021
    First version publication date
    21 Dec 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GH29914
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02670044
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.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
    10 Dec 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Dec 2020
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the safety and tolerability of Venetoclax in combination with Cobimetinib and Venetoclax in combination with Idasanutlin
    Protection of trial subjects
    All subjects were required to sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Mar 2016
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 1 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 18
    Country: Number of subjects enrolled
    France: 14
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    United States: 44
    Worldwide total number of subjects
    88
    EEA total number of subjects
    26
    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)
    11
    From 65 to 84 years
    72
    85 years and over
    5

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 17 centers in 4 countries.

    Pre-assignment
    Screening details
    		 A total of 88 subjects were randomized in this study. Of these, 85 subjects received at least one dose of any study drug.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg)
    Arm description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cobimetinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Cobimetinib was administered orally once daily (QD) at a dose of 40mg on Days 1-21 of each 28-day treatment cycle.

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax was administered orally once daily (QD) at a dose of 400mg on Days 1-28 of each 28 day treatment cycle.

    Arm title
    		 Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg)
    Arm description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax was administered orally once daily (QD) at a dose of 600mg on Days 1-28 of each 28 day treatment cycle.

    Investigational medicinal product name
    Cobimetinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Cobimetinib was administered orally once daily (QD) at a dose of 40mg on Days 1-21 of each 28-day treatment cycle.

    Arm title
    		 Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg)
    Arm description
    		 Subjects received Venetoclax 800mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cobimetinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Cobimetinib was administered orally once daily (QD) at a dose of 40mg on Days 1-21 of each 28-day treatment cycle.

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax was administered orally once daily (QD) at a dose of 800mg on Days 1-28 of each 28 day treatment cycle.

    Arm title
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg)
    Arm description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 60mg daily on Days 1-21 of each 28-day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cobimetinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Cobimetinib was administered orally once daily (QD) at a dose of 60mg on Days 1-21 of each 28-day treatment cycle.

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax was administered orally once daily (QD) at a dose of 400mg on Days 1-28 of each 28 day treatment cycle.

    Arm title
    		 Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg)
    Arm description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax was administered orally once daily (QD) at a dose of 400mg on Days 1-28 of each 28 day treatment cycle.

    Investigational medicinal product name
    Idasanutlin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Idasanutlin was administered orally once daily (QD) or twice daily (BID) at a dose of 200mg on Days 1-5 of each 28 day treatment cycle.

    Arm title
    		 Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg)
    Arm description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 150mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax was administered orally once daily (QD) at a dose of 600mg on Days 1-28 of each 28 day treatment cycle.

    Investigational medicinal product name
    Idasanutlin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Idasanutlin was administered orally once daily (QD) or twice daily (BID) at a dose of 150mg on Days 1-5 of each 28 day treatment cycle.

    Arm title
    		 Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg)
    Arm description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax was administered orally once daily (QD) at a dose of 600mg on Days 1-28 of each 28 day treatment cycle.

    Investigational medicinal product name
    Idasanutlin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Idasanutlin was administered orally once daily (QD) or twice daily (BID) at a dose of 200mg on Days 1-5 of each 28 day treatment cycle.

    Arm title
    		 Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg)
    Arm description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 400mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax was administered orally once daily (QD) at a dose of 400mg on Days 1-28 of each 28 day treatment cycle.

    Investigational medicinal product name
    Idasanutlin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Idasanutlin was administered orally once daily (QD) or twice daily (BID) at a dose of 400mg on Days 1-5 of each 28 day treatment cycle.

    Arm title
    		 Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Arm description
    		 Subjects received Venetoclax 600mg daily on Days 1-21 of each 28 day treatment cycle and Idasanutlin 150mg daily on Days 1-5 of each 28 day treatment cycle.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Idasanutlin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Idasanutlin was administered orally once daily (QD) at a dose of 150mg on Days 1-5 of each 28 day treatment cycle.

    Investigational medicinal product name
    Venetoclax
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Venetoclax was administered orally once daily (QD) at a dose of 600mg on Days 1-21 of each 28 day treatment cycle.

    Number of subjects in period 1
    		Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Started
    4
    8
    12
    8
    6
    13
    22
    9
    6
    Completed
    0
    1
    0
    0
    1
    0
    3
    0
    0
    Not completed
    4
    7
    12
    8
    5
    13
    19
    9
    6
         Consent withdrawn by subject
    -
    1
    2
    -
    -
    1
    1
    1
    -
         Death
    4
    6
    10
    6
    5
    11
    17
    7
    2
         Progressive Disease
    -
    -
    -
    -
    -
    1
    -
    -
    -
         Multiple Reasons
    -
    -
    -
    1
    -
    -
    1
    -
    -
         Study Terminated by Sponsor
    -
    -
    -
    -
    -
    -
    -
    -
    4
         Lost to follow-up
    -
    -
    -
    1
    -
    -
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg)
    Reporting group description
    		 Subjects received Venetoclax 800mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 60mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 150mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 400mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-21 of each 28 day treatment cycle and Idasanutlin 150mg daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg) Total
    Number of subjects
    		 4 8 12 8 6 13 22 9 6 88
    Age Categorical
    Units: Subjects
        In utero
    		 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
        Newborns (0-27 days)
    		 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
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 0 2 1 1 1 3 0 1 2 11
        From 65-84 years
    		 4 6 11 7 3 10 19 8 4 72
        85 years and over
    		 0 0 0 0 2 0 3 0 0 5
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 72.3 ( 3.8 ) 70.9 ( 6.6 ) 73.5 ( 6.6 ) 70.4 ( 6.3 ) 75.8 ( 11.4 ) 71.4 ( 5.6 ) 75.1 ( 7.0 ) 73.9 ( 6.6 ) 63.5 ( 14.7 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 2 4 7 2 1 4 9 4 4 37
        Male
    		 2 4 5 6 5 9 13 5 2 51
    Race/Ethnicity, Customized
    Race
    Units: Subjects
        Asian
    		 0 1 1 1 0 0 1 0 0 4
        Black or African American
    		 0 0 2 0 0 1 0 0 0 3
        White
    		 1 7 9 5 6 11 15 8 6 68
        Unknown
    		 3 0 0 2 0 1 6 1 0 13
    Race/Ethnicity, Customized
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 1 0 1 0 0 2 0 0 1 5
        Not Hispanic or Latino
    		 2 7 11 7 6 9 15 7 5 69
        Not Stated
    		 1 1 0 1 0 2 7 2 0 14

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg)
    Reporting group description
    		 Subjects received Venetoclax 800mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 60mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 150mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 400mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-21 of each 28 day treatment cycle and Idasanutlin 150mg daily on Days 1-5 of each 28 day treatment cycle.

    Subject analysis set title
    Arm A (Venetoclax + Cobimetinib) (PRO Analysis)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received Venetoclax daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib daily on Days 1-21 of each 28-day treatment cycle.

    Subject analysis set title
    Arm B (Venetoclax + Idasanutlin) (PRO Analysis)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received Venetoclax on Days 1-28 of each 28 day treatment cycle and Idasanutlin daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Subject analysis set title
    Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) (PK)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Subject analysis set title
    Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) (PK)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Subject analysis set title
    Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) (PK)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received Venetoclax 800mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Subject analysis set title
    Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) (PK)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 60mg daily on Days 1-21 of each 28-day treatment cycle.

    Subject analysis set title
    Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) (PK)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Subject analysis set title
    Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) (PK)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 150mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Subject analysis set title
    Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) (PK)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Subject analysis set title
    Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) (PK)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 400mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Subject analysis set title
    Dose Optim: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg) (PK)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received Venetoclax 600mg daily on Days 1-21 of each 28 day treatment cycle and Idasanutlin 150mg daily on Days 1-5 of each 28 day treatment cycle.

    Primary: Number of Subjects with Dose Limiting Toxicities (DLTs)

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    End point title
    		 Number of Subjects with Dose Limiting Toxicities (DLTs) [1]
    End point description
    End point type
    Primary
    End point timeframe
    From Cycle 1 Day 1 to Cycle 2 Day 1 for a minimum of 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: No Statistical analyses performed on safety data.
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    4
    7
    12
    7
    6
    13
    21
    9
    0 [2]
    Units: Subjects
        number (not applicable)
    0
    1
    1
    2
    0
    2
    2
    2
    Notes
    [2] - Cohort was not assessed for DLTs. Not considered part of dose escalation.
    No statistical analyses for this end point

    Primary: Number of Subjects with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

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    End point title
    		 Number of Subjects with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) [3]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline up until 30 days after the last dose of study drug (up to a maximum of 4 years, 9 months)
    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: No Statistical analyses performed on safety data.
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    4
    7
    12
    7
    6
    13
    21
    9
    6
    Units: Subjects
    number (not applicable)
        AEs
    4
    7
    12
    7
    6
    13
    21
    9
    6
        SAEs
    2
    4
    11
    7
    5
    11
    16
    8
    5
        AESIs
    3
    5
    11
    6
    4
    11
    15
    7
    6
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR) (Complete remission (CR) + Complete Remission with Incomplete Blood Count Recovery (CRi) + Incomplete Platelet Count Recovery (CRp) + Partial Remission/Partial Response [PR])

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    End point title
    		 Overall Response Rate (ORR) (Complete remission (CR) + Complete Remission with Incomplete Blood Count Recovery (CRi) + Incomplete Platelet Count Recovery (CRp) + Partial Remission/Partial Response [PR])
    End point description
    ORR is defined as the proportion of subjects who achieved a CR, CRi, CRp or partial remission/partial response (PR).
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    4
    8
    12
    8
    6
    13
    22
    9
    6
    Units: Subjects
        number (not applicable)
    1
    1
    2
    1
    1
    5
    7
    1
    2
    No statistical analyses for this end point

    Secondary: Complete remission/complete response (CR) + Complete remission with incomplete blood count recovery (CRi) + Complete remission with incomplete platelet count recovery (CRp)

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    End point title
    		 Complete remission/complete response (CR) + Complete remission with incomplete blood count recovery (CRi) + Complete remission with incomplete platelet count recovery (CRp)
    End point description
    Defined as the proportion of subjects who achieved a CR, CRi, or CRp.
    End point type
    Secondary
    End point timeframe
    Up to 2 years.
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    4
    8
    12
    8
    6
    13
    22
    9
    6
    Units: Subjects
        number (not applicable)
    1
    1
    2
    1
    1
    5
    7
    0
    2
    No statistical analyses for this end point

    Secondary: CR + Complete Remission with Partial Hematologic Recovery (CRh) Rate

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    End point title
    		 CR + Complete Remission with Partial Hematologic Recovery (CRh) Rate
    End point description
    Please note that for this Outcome Measure, an insufficient number of subjects were analysed meaning that the data collected was minimal and not sufficient to generate the Statistical (Number) values.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    0 [4]
    0 [5]
    0 [6]
    0 [7]
    0 [8]
    0 [9]
    0 [10]
    0 [11]
    0 [12]
    Units: Subjects
        number (not applicable)
    Notes
    [4] - Insufficient number of subjects analysed.
    [5] - Insufficient number of subjects analysed.
    [6] - Insufficient number of subjects analysed.
    [7] - Insufficient number of subjects analysed.
    [8] - Insufficient number of subjects analysed.
    [9] - Insufficient number of subjects analysed.
    [10] - Insufficient number of subjects analysed.
    [11] - Insufficient number of subjects analysed.
    [12] - Insufficient number of subjects analysed.
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    DOR is defined as the number of days from the date of first response (CR, CRi, CRp or PR) to the earliest recurrence, disease progression or death. 0000/9999 = Not Estimable.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    1
    1
    2
    1
    1
    5
    7
    1
    2
    Units: Months
        median (confidence interval 95%)
    2.0 (0000 to 9999)
    4.4 (0000 to 9999)
    2.6 (1.0 to 4.2)
    10.4 (0000 to 9999)
    9999 (0000 to 9999)
    6.0 (2.2 to 12.5)
    4.9 (1.9 to 8.8)
    0.6 (0000 to 9999)
    9999 (1.0 to 9999)
    No statistical analyses for this end point

    Secondary: Time to Progression (TTP)

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    End point title
    		 Time to Progression (TTP)
    End point description
    TTP is defined as the number of days from the date of first treatment to the date of earliest disease progression. 0000/9999 = Not Estimable.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    1
    2
    4
    0 [13]
    3
    4
    13
    2
    2
    Units: Months
        median (confidence interval 95%)
    4.9 (0000 to 9999)
    4.5 (3.2 to 5.8)
    2.8 (0.9 to 7.4)
    ( to )
    1.7 (0.9 to 6.7)
    7.1 (3.0 to 12.4)
    4.4 (3.3 to 5.9)
    7.7 (1.2 to 14.2)
    3.8 (1.8 to 5.8)
    Notes
    [13] - No subjects analysed in this arm.
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS)

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    End point title
    		 Progression-Free Survival (PFS)
    End point description
    Please note that for this Outcome Measure, an insufficient number of PFS Events meant that this insufficient data could not be analysed and therefore, the Statistical (Median and Lower Limit/Upper Limit Confidence Interval (CI)) values could not be generated.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    0 [14]
    0 [15]
    0 [16]
    0 [17]
    0 [18]
    0 [19]
    0 [20]
    0 [21]
    0 [22]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [14] - No subjects were analysed for median and CI.
    [15] - No subjects were analysed for median and CI.
    [16] - No subjects were analysed for median and CI.
    [17] - No subjects were analysed for median and CI.
    [18] - No subjects were analysed for median and CI.
    [19] - No subjects were analysed for median and CI.
    [20] - No subjects were analysed for median and CI.
    [21] - No subjects were analysed for median and CI.
    [22] - No subjects were analysed for median and CI.
    No statistical analyses for this end point

    Secondary: Event-Free Survival (EFS)

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    End point title
    		 Event-Free Survival (EFS)
    End point description
    EFS is defined for all subjects and measured from the date of first treatment until treatment failure, relapse from CR, CRp or CRi or death from any cause, whichever occurs first.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    4
    8
    12
    8
    6
    13
    22
    9
    6
    Units: Months
        median (confidence interval 95%)
    0.9 (0.9 to 4.7)
    2.8 (1.6 to 3.2)
    2.5 (1.4 to 7.1)
    1.8 (1.0 to 12.3)
    1.9 (1.7 to 6.7)
    3.8 (3.2 to 6.2)
    3.6 (2.3 to 5.5)
    2.8 (1.5 to 4.4)
    3.8 (1.8 to 5.8)
    No statistical analyses for this end point

    Secondary: Leukemia-Free Survival (LFS)

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    End point title
    		 Leukemia-Free Survival (LFS)
    End point description
    Please note that for this Outcome Measure, an insufficient number of LFS Events meant that this insufficient data could not be analysed and therefore, the Statistical (Median and Lower Limit/Upper Limit Confidence Interval (CI)) values could not be generated.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    0 [23]
    0 [24]
    0 [25]
    0 [26]
    0 [27]
    0 [28]
    0 [29]
    0 [30]
    0 [31]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [23] - No subjects were analysed for median and CI.
    [24] - No subjects were analysed for median and CI.
    [25] - No subjects were analysed for median and CI.
    [26] - No subjects were analysed for median and CI.
    [27] - No subjects were analysed for median and CI.
    [28] - No subjects were analysed for median and CI.
    [29] - No subjects were analysed for median and CI.
    [30] - No subjects were analysed for median and CI.
    [31] - No subjects were analysed for median and CI.
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the number of days from the date of first treatment to the date of death from any cause for all subjects. 9999 = Not Estimable.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    4
    8
    12
    8
    6
    13
    22
    9
    6
    Units: Months
        median (confidence interval 95%)
    4.7 (1.6 to 8.7)
    5.9 (2.1 to 14.2)
    3.4 (1.6 to 9.3)
    2.8 (1.0 to 8.6)
    2.3 (1.9 to 10.2)
    5.3 (3.4 to 13.7)
    6.3 (3.9 to 9.8)
    3.1 (1.8 to 4.4)
    9999 (4.1 to 9999)
    No statistical analyses for this end point

    Secondary: Pharmacokinetics of Venetoclax Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr)

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    End point title
    		 Pharmacokinetics of Venetoclax Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr)
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 6 months
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) (PK) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) (PK) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) (PK) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) (PK) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) (PK) Dose Optim: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg) (PK)
    Number of subjects analysed
    4
    7
    8
    3
    6
    11
    19
    8
    5
    Units: μg·hr/mL
        arithmetic mean (full range (min-max))
    20.8 (11.2 to 30.0)
    21.7 (7.54 to 43.0)
    24.9 (13.4 to 47.3)
    22.9 (18.2 to 29.2)
    14.9 (3.68 to 31.5)
    21.6 (7.76 to 50.1)
    16.6 (6.03 to 34.5)
    22.2 (3.46 to 80.7)
    21.8 (10.1 to 33.2)
    No statistical analyses for this end point

    Secondary: Pharmacokinetics of Venetoclax Maximum Observed Concentration (Cmax)

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    End point title
    		 Pharmacokinetics of Venetoclax Maximum Observed Concentration (Cmax)
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 6 months
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) (PK) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) (PK) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) (PK) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) (PK) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) (PK) Dose Optim: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg) (PK)
    Number of subjects analysed
    4
    7
    8
    3
    6
    11
    19
    8
    5
    Units: μg/mL
        arithmetic mean (full range (min-max))
    1.34 (0.85 to 1.65)
    1.48 (0.88 to 2.43)
    1.64 (0.80 to 2.90)
    1.16 (0.96 to 1.43)
    1.11 (0.26 to 1.88)
    1.47 (0.69 to 3.54)
    1.15 (0.34 to 2.09)
    1.04 (0.22 to 1.95)
    1.45 (0.74 to 2.00)
    No statistical analyses for this end point

    Secondary: Pharmacokinetics of Cobimetinib Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr)

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    End point title
    		 Pharmacokinetics of Cobimetinib Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr)
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 6 months
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) (PK)
    Number of subjects analysed
    4
    7
    8
    3
    Units: μg·hr/mL
        arithmetic mean (full range (min-max))
    5.30 (2.40 to 12.9)
    3.21 (0.46 to 5.51)
    6.34 (2.25 to 11.7)
    12.6 (6.0 to 16.0)
    No statistical analyses for this end point

    Secondary: Pharmacokinetics of Cobimetinib Maximum Observed Concentration (Cmax)

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    End point title
    		 Pharmacokinetics of Cobimetinib Maximum Observed Concentration (Cmax)
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 6 months
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) (PK) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) (PK)
    Number of subjects analysed
    4
    7
    8
    3
    Units: μg/mL
        arithmetic mean (full range (min-max))
    0.32 (0.16 to 0.76)
    0.20 (0.089 to 0.30)
    0.39 (0.20 to 0.62)
    0.64 (0.31 to 0.81)
    No statistical analyses for this end point

    Secondary: Pharmacokinetics of Idasanutlin Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr)

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    End point title
    		 Pharmacokinetics of Idasanutlin Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr)
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 6 months
    End point values
    		 Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) (PK) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) (PK) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) (PK) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) (PK) Dose Optim: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg) (PK)
    Number of subjects analysed
    6
    11
    19
    8
    5
    Units: μg·hr/mL
        arithmetic mean (full range (min-max))
    66.2 (19.2 to 142)
    67.5 (24.3 to 135)
    70.1 (29.6 to 124)
    132 (32.5 to 280)
    59.1 (30.6 to 73.9)
    No statistical analyses for this end point

    Secondary: Pharmacokinetics of Idasanutlin Maximum Observed Concentration (Cmax)

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    End point title
    		 Pharmacokinetics of Idasanutlin Maximum Observed Concentration (Cmax)
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 6 months
    End point values
    		 Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) (PK) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) (PK) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) (PK) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) (PK) Dose Optim: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg) (PK)
    Number of subjects analysed
    6
    11
    19
    8
    5
    Units: μg/mL
        arithmetic mean (full range (min-max))
    3.77 (1.16 to 8.74)
    3.76 (1.63 to 7.42)
    4.13 (1.51 to 7.37)
    7.11 (1.39 to 16.3)
    3.22 (1.86 to 3.93)
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire

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    End point title
    		 Number of Subjects Reporting Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire
    End point description
    (n=X; n=X) represents the number of subjects analysed at each timepoint.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Arm A (Venetoclax + Cobimetinib) (PRO Analysis) Arm B (Venetoclax + Idasanutlin) (PRO Analysis)
    Number of subjects analysed
    15
    11
    Units: Subjects
    number (not applicable)
        Nausea frequency (n=14; n=9)
    63.6
    52.9
        Diarrhoea frequency (n=15; n=11)
    68.2
    64.7
        Decreased appetite severity (n=14; n=10)
    63.6
    58.8
        Vomiting severity (n=8; n=8)
    36.4
    47.1
    No statistical analyses for this end point

    Secondary: Rate of Transfusion Independence

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    End point title
    		 Rate of Transfusion Independence
    End point description
    Please note that for this Outcome Measure, an insufficient number of subjects were analysed meaning that the data collected was minimal and not sufficient to generate the Statistical (Number) values.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    0 [32]
    0 [33]
    0 [34]
    0 [35]
    0 [36]
    0 [37]
    0 [38]
    0 [39]
    0 [40]
    Units: Subjects
        number (not applicable)
    Notes
    [32] - Insufficient number of subjects analysed.
    [33] - Insufficient number of subjects analysed.
    [34] - Insufficient number of subjects analysed.
    [35] - Insufficient number of subjects analysed.
    [36] - Insufficient number of subjects analysed.
    [37] - Insufficient number of subjects analysed.
    [38] - Insufficient number of subjects analysed.
    [39] - Insufficient number of subjects analysed.
    [40] - Insufficient number of subjects analysed.
    No statistical analyses for this end point

    Secondary: Duration Of Transfusion Independence, Defined As The Number Of Consecutive Days Of Transfusion Independence, Measured From 1 Day After Last Transfusion To Disease Progression Or Subsequent Transfusion

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    End point title
    		 Duration Of Transfusion Independence, Defined As The Number Of Consecutive Days Of Transfusion Independence, Measured From 1 Day After Last Transfusion To Disease Progression Or Subsequent Transfusion
    End point description
    Please note that for this Outcome Measure, an insufficient number of subjects were analysed meaning that the data collected was minimal and not sufficient to generate the Statistical (Number) values.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    0 [41]
    0 [42]
    0 [43]
    0 [44]
    0 [45]
    0 [46]
    0 [47]
    0 [48]
    0 [49]
    Units: Days
        number (not applicable)
    Notes
    [41] - Insufficient number of subjects analysed.
    [42] - Insufficient number of subjects analysed.
    [43] - Insufficient number of subjects analysed.
    [44] - Insufficient number of subjects analysed.
    [45] - Insufficient number of subjects analysed.
    [46] - Insufficient number of subjects analysed.
    [47] - Insufficient number of subjects analysed.
    [48] - Insufficient number of subjects analysed.
    [49] - Insufficient number of subjects analysed.
    No statistical analyses for this end point

    Secondary: Minimal Residual Disease (MRD) In The Bone Marrow To Evaluate The Depth Of Response

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    End point title
    		 Minimal Residual Disease (MRD) In The Bone Marrow To Evaluate The Depth Of Response
    End point description
    Please note that for this Outcome Measure, an insufficient number of subjects were analysed meaning that the data collected was minimal and not sufficient to generate the Statistical (Number) values.
    End point type
    Secondary
    End point timeframe
    Up to 2 years
    End point values
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Number of subjects analysed
    0 [50]
    0 [51]
    0 [52]
    0 [53]
    0 [54]
    0 [55]
    0 [56]
    0 [57]
    0 [58]
    Units: Subjects
        number (not applicable)
    Notes
    [50] - Insufficient number of subjects analysed.
    [51] - Insufficient number of subjects analysed.
    [52] - Insufficient number of subjects analysed.
    [53] - Insufficient number of subjects analysed.
    [54] - Insufficient number of subjects analysed.
    [55] - Insufficient number of subjects analysed.
    [56] - Insufficient number of subjects analysed.
    [57] - Insufficient number of subjects analysed.
    [58] - Insufficient number of subjects analysed.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up until 30 days after the last dose of study drug (up to a maximum of 4 years, 9 months)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18
    Reporting groups
    Reporting group title
    Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg)
    Reporting group description
    		 Subjects received Venetoclax 800mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 60mg daily on Days 1-21 of each 28-day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 150mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg)
    Reporting group description
    		 Subjects received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 400mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.

    Reporting group title
    Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Reporting group description
    		 Subjects received Venetoclax 600mg daily on Days 1-21 of each 28 day treatment cycle and Idasanutlin 150mg daily on Days 1-5 of each 28 day treatment cycle.

    Serious adverse events
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 4 (50.00%)
    4 / 7 (57.14%)
    11 / 12 (91.67%)
    7 / 7 (100.00%)
    5 / 6 (83.33%)
    11 / 13 (84.62%)
    16 / 21 (76.19%)
    8 / 9 (88.89%)
    5 / 6 (83.33%)
         number of deaths (all causes)
    4
    6
    10
    6
    5
    13
    17
    7
    2
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    ORTHOSTATIC HYPOTENSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    PYREXIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FATIGUE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    ASTHENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    MULTIPLE ORGAN DYSFUNCTION SYNDROME
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    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%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Immune system disorders
    HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    PROSTATITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    PLEURAL EFFUSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMOPTYSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG DISORDER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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 / 1
    0 / 0
    0 / 0
    Psychiatric disorders
    CONFUSIONAL STATE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    Investigations
    WHITE BLOOD CELL COUNT INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    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
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    EJECTION FRACTION DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    2 / 12 (16.67%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    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
    TROPONIN I INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    POST PROCEDURAL HAEMATOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FALL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    CARDIAC FAILURE CHRONIC
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    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 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    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 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARDIO-RESPIRATORY ARREST
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    PERICARDIAL EFFUSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARDIAC FAILURE CONGESTIVE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ACUTE CORONARY SYNDROME
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    CEREBRAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NERVOUS SYSTEM DISORDER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    5 / 12 (41.67%)
    3 / 7 (42.86%)
    2 / 6 (33.33%)
    8 / 13 (61.54%)
    5 / 21 (23.81%)
    3 / 9 (33.33%)
    2 / 6 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    2 / 8
    0 / 6
    1 / 2
    4 / 11
    3 / 7
    3 / 3
    0 / 3
         deaths causally related to treatment / all
    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 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    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 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    CHALAZION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    DYSPHAGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    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
    GASTRIC HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    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 / 7 (14.29%)
    2 / 12 (16.67%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    2 / 2
    0 / 0
    0 / 0
    1 / 1
    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
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHOIDS THROMBOSED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIC COLITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    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
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    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
    UPPER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLECYSTITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    CHONDROCALCINOSIS PYROPHOSPHATE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ARTHRALGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    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
    Infections and infestations
    ENTEROCOCCAL INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    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 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMOCYSTIS JIROVECII PNEUMONIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHOPULMONARY ASPERGILLOSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BACTERAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HORDEOLUM
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA NECROTISING
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ACUTE HAEMORRHAGIC CONJUNCTIVITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SINUSITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    ARTHRITIS BACTERIAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    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
    ESCHERICHIA SEPSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA BACTERIAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    ESCHERICHIA BACTERAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    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
    HERPES ZOSTER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SYSTEMIC CANDIDA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    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
    TOOTH INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA FUNGAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    5 / 12 (41.67%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    3 / 21 (14.29%)
    3 / 9 (33.33%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 5
    0 / 1
    0 / 0
    0 / 2
    0 / 3
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 7 (28.57%)
    3 / 12 (25.00%)
    3 / 7 (42.86%)
    2 / 6 (33.33%)
    2 / 13 (15.38%)
    2 / 21 (9.52%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 5
    0 / 2
    2 / 4
    1 / 5
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL BACTERAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    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 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    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%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    2 / 9 (22.22%)
    2 / 6 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FUNGAL INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    3 / 3
    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
    STAPHYLOCOCCAL INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    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 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    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
    HEPATOSPLENIC CANDIDIASIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    HYPOPHAGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FAILURE TO THRIVE
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEHYDRATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    DECREASED APPETITE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (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
         deaths causally related to treatment / all
    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
    		 Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg) Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg) Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg) Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg) Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    7 / 7 (100.00%)
    12 / 12 (100.00%)
    7 / 7 (100.00%)
    6 / 6 (100.00%)
    13 / 13 (100.00%)
    21 / 21 (100.00%)
    9 / 9 (100.00%)
    6 / 6 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    NEOPLASM
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    LEUKAEMIA CUTIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    MONOCLONAL GAMMOPATHY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    SQUAMOUS CELL CARCINOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    Vascular disorders
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    THROMBOPHLEBITIS SUPERFICIAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    FLUSHING
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    HAEMATOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    PHLEBITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    HYPOTENSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    4 / 21 (19.05%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    1
    5
    2
    0
    ORTHOSTATIC HYPOTENSION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    HYPERTENSION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    1
    1
    1
    1
    0
    0
    2
    General disorders and administration site conditions
    CHILLS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    2 / 12 (16.67%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    4 / 13 (30.77%)
    3 / 21 (14.29%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    7
    4
    2
    0
    PYREXIA
         subjects affected / exposed
    0 / 4 (0.00%)
    3 / 7 (42.86%)
    2 / 12 (16.67%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    4 / 13 (30.77%)
    3 / 21 (14.29%)
    3 / 9 (33.33%)
    1 / 6 (16.67%)
         occurrences all number
    0
    3
    2
    1
    0
    6
    3
    3
    2
    FATIGUE
         subjects affected / exposed
    1 / 4 (25.00%)
    6 / 7 (85.71%)
    4 / 12 (33.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    4 / 13 (30.77%)
    8 / 21 (38.10%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
         occurrences all number
    1
    6
    4
    4
    0
    5
    10
    1
    1
    CYST
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    1
    MALAISE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    LOCALISED OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    1
    0
    0
    FACIAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    GENERALISED OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    1
    0
    0
    SUPRAPUBIC PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    MEDICAL DEVICE PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    ASTHENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    4 / 13 (30.77%)
    2 / 21 (9.52%)
    5 / 9 (55.56%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    1
    1
    0
    4
    2
    8
    2
    CHEST PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    3 / 4 (75.00%)
    2 / 7 (28.57%)
    0 / 12 (0.00%)
    4 / 7 (57.14%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    7 / 21 (33.33%)
    3 / 9 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    3
    2
    0
    4
    0
    3
    7
    4
    0
    PERIPHERAL SWELLING
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    0
    0
    0
    0
    Immune system disorders
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    GENITAL LESION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    PELVIC PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    PROSTATITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    VAGINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    SCROTAL OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    PRODUCTIVE COUGH
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    0
    THROAT IRRITATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    DYSPNOEA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    4 / 13 (30.77%)
    4 / 21 (19.05%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    5
    4
    2
    0
    RALES
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    4
    0
    1
    0
    LOWER RESPIRATORY TRACT CONGESTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    HYPOXIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    1
    0
    0
    RHINORRHOEA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    0
    0
    TACHYPNOEA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    SINUS CONGESTION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    PLEURAL EFFUSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    1
    0
    RHONCHI
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    EPISTAXIS
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 7 (28.57%)
    2 / 12 (16.67%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    3 / 21 (14.29%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    2
    2
    1
    0
    1
    4
    0
    0
    THROAT TIGHTNESS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    UPPER-AIRWAY COUGH SYNDROME
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    COUGH
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    3 / 13 (23.08%)
    5 / 21 (23.81%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    4
    6
    0
    0
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    WHEEZING
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    1
    0
    0
    PULMONARY VASCULAR DISORDER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    PULMONARY OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    1
    0
    0
    HAEMOPTYSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    0
    0
    HICCUPS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    1
    DYSPHONIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    1
    0
    0
    PLEURITIC PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    PULMONARY MASS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    1
    0
    0
    RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Psychiatric disorders
    DEPRESSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    INSOMNIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    3 / 21 (14.29%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    3
    1
    1
    CONFUSIONAL STATE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    3 / 21 (14.29%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    0
    0
    0
    2
    3
    0
    1
    DELIRIUM
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    ANXIETY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    4 / 13 (30.77%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    4
    0
    1
    1
    Investigations
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    3 / 21 (14.29%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    5
    0
    0
    PROTHROMBIN TIME PROLONGED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    URINE OUTPUT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    ANTITHROMBIN III DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    0
    1
    2
    0
    0
    3
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    5 / 21 (23.81%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    1
    1
    0
    3
    5
    2
    0
    BLOOD CREATINE PHOSPHOKINASE INCREASED
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    0
    BREATH SOUNDS ABNORMAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    TROPONIN I INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    WEIGHT DECREASED
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    2 / 21 (9.52%)
    2 / 9 (22.22%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    0
    1
    0
    3
    2
    2
    1
    PLATELET COUNT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    3
    0
    0
    CARDIAC MURMUR
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    ELECTROCARDIOGRAM QT PROLONGED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    SERUM FERRITIN INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    WHITE BLOOD CELL COUNT INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    BLOOD PHOSPHORUS INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    4
    0
    0
    0
    BLOOD PRESSURE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    INTERNATIONAL NORMALISED RATIO INCREASED
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 7 (28.57%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    1
    0
    0
    1
    0
    0
    0
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    1
    0
    1
    1
    1
    0
    BLOOD LACTIC ACID INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    1
    0
    0
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    4 / 21 (19.05%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    1
    2
    0
    2
    4
    2
    0
    WEIGHT INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    1
    1
    0
    0
    0
    0
    EJECTION FRACTION DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    1
    0
    0
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
    2 / 21 (9.52%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    0
    1
    1
    2
    2
    2
    0
    GAMMA-GLUTAMYLTRANSFERASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    LYMPHOCYTE COUNT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    TROPONIN INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    BLOOD CHLORIDE INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    2 / 21 (9.52%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    0
    3
    2
    1
    1
    C-REACTIVE PROTEIN INCREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    TRANSFUSION REACTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    1
    0
    PERIORBITAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    SKIN LACERATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    ARTHROPOD BITE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    INFUSION RELATED REACTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    POST PROCEDURAL ERYTHEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    FALL
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    2 / 12 (16.67%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    2
    2
    0
    0
    1
    0
    1
    POST PROCEDURAL FEVER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    CONTUSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    2 / 13 (15.38%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    0
    1
    2
    0
    0
    1
    Cardiac disorders
    SINUS TACHYCARDIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    1
    TACHYCARDIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    2
    1
    0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    3 / 9 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    3
    0
    BRADYCARDIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    LEFT VENTRICULAR DYSFUNCTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    SINUS BRADYCARDIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    CARDIAC FAILURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Nervous system disorders
    TRANSIENT APHASIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    LETHARGY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    DYSGEUSIA
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    0
    0
    0
    0
    SYNCOPE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    0
    1
    0
    SOMNOLENCE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    DIZZINESS
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    3 / 13 (23.08%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    0
    1
    0
    3
    1
    0
    2
    HEMIPARESIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    TREMOR
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    2
    1
    0
    0
    RESTLESS LEGS SYNDROME
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    COGNITIVE DISORDER
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    HEADACHE
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    5 / 21 (23.81%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    3
    5
    1
    0
    DIABETIC NEUROPATHY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    PRESYNCOPE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    HYPOGEUSIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    LYMPHOPENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    COAGULOPATHY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    BONE MARROW FAILURE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    LYMPHADENOPATHY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    NEUTROPENIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    2 / 6 (33.33%)
    4 / 13 (30.77%)
    5 / 21 (23.81%)
    3 / 9 (33.33%)
    3 / 6 (50.00%)
         occurrences all number
    1
    0
    0
    1
    2
    5
    7
    6
    7
    ANAEMIA
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    3 / 13 (23.08%)
    8 / 21 (38.10%)
    1 / 9 (11.11%)
    3 / 6 (50.00%)
         occurrences all number
    3
    2
    1
    0
    0
    6
    8
    1
    3
    DISSEMINATED INTRAVASCULAR COAGULATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    3 / 12 (25.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    4 / 21 (19.05%)
    2 / 9 (22.22%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    3
    1
    0
    4
    5
    2
    1
    THROMBOCYTOPENIA
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 7 (14.29%)
    2 / 12 (16.67%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    3 / 13 (23.08%)
    7 / 21 (33.33%)
    3 / 9 (33.33%)
    3 / 6 (50.00%)
         occurrences all number
    2
    1
    2
    0
    1
    10
    7
    5
    4
    LEUKOPENIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    0
    1
    0
    0
    LYMPH NODE PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    SPLENOMEGALY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    LEUKOCYTOSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    0
    Ear and labyrinth disorders
    EAR PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    EAR CONGESTION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Eye disorders
    VISION BLURRED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    VITREOUS HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    PERIORBITAL OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    MACULAR OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    PERIORBITAL SWELLING
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    DIABETIC RETINOPATHY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    ORBITAL OEDEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    RETINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    2 / 12 (16.67%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    2
    0
    0
    0
    1
    0
    0
    VITREOUS DETACHMENT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    CONJUNCTIVAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    DRY EYE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    0
    RETINAL DRUSEN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    OPTIC DISC DISORDER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    NORMAL TENSION GLAUCOMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    BLEPHARITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    CATARACT
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    MELAENA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    CONSTIPATION
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    7 / 12 (58.33%)
    2 / 7 (28.57%)
    2 / 6 (33.33%)
    4 / 13 (30.77%)
    4 / 21 (19.05%)
    1 / 9 (11.11%)
    2 / 6 (33.33%)
         occurrences all number
    1
    1
    7
    3
    2
    5
    4
    1
    3
    VOMITING
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 7 (28.57%)
    3 / 12 (25.00%)
    5 / 7 (71.43%)
    2 / 6 (33.33%)
    7 / 13 (53.85%)
    14 / 21 (66.67%)
    3 / 9 (33.33%)
    3 / 6 (50.00%)
         occurrences all number
    2
    2
    4
    11
    5
    13
    25
    3
    4
    HAEMATOCHEZIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    TONGUE DISCOLOURATION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    DRY MOUTH
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    2 / 12 (16.67%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    3 / 21 (14.29%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    1
    3
    2
    0
    ILEUS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    RECTAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    1
    0
    0
    HAEMORRHOIDS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    3 / 13 (23.08%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    1
    0
    0
    4
    0
    1
    2
    ABDOMINAL DISCOMFORT
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    HAEMORRHOIDAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    0
    GASTRIC HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    COLITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    2 / 12 (16.67%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    1
    0
    0
    DIARRHOEA
         subjects affected / exposed
    4 / 4 (100.00%)
    5 / 7 (71.43%)
    7 / 12 (58.33%)
    6 / 7 (85.71%)
    6 / 6 (100.00%)
    12 / 13 (92.31%)
    18 / 21 (85.71%)
    8 / 9 (88.89%)
    4 / 6 (66.67%)
         occurrences all number
    5
    14
    15
    15
    15
    26
    44
    15
    6
    ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    2
    1
    2
    0
    ANAL INCONTINENCE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    1
    0
    0
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    DYSPHAGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    0
    0
    0
    GINGIVAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    MOUTH HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    2 / 21 (9.52%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    1
    0
    FLATULENCE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    2
    0
    1
    0
    GINGIVAL HYPERTROPHY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    ORAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    2 / 12 (16.67%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    1
    0
    0
    1
    0
    0
    DIVERTICULUM
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    STOMATITIS
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    2 / 12 (16.67%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    3
    1
    0
    1
    2
    0
    0
    DIVERTICULUM GASTRIC
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    GINGIVAL BLEEDING
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    TOOTHACHE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    LIP BLISTER
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    NAUSEA
         subjects affected / exposed
    2 / 4 (50.00%)
    4 / 7 (57.14%)
    6 / 12 (50.00%)
    6 / 7 (85.71%)
    5 / 6 (83.33%)
    11 / 13 (84.62%)
    16 / 21 (76.19%)
    6 / 9 (66.67%)
    3 / 6 (50.00%)
         occurrences all number
    3
    5
    7
    9
    9
    18
    31
    9
    6
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    1 / 12 (8.33%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    3 / 13 (23.08%)
    4 / 21 (19.05%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    1
    2
    0
    4
    6
    1
    0
    ODYNOPHAGIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    0
    PROCTALGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    DYSPEPSIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    1
    0
    0
    Hepatobiliary disorders
    CHOLESTASIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    HEPATOCELLULAR INJURY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    CHOLECYSTITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    OCULAR ICTERUS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    HYPERBILIRUBINAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    2 / 21 (9.52%)
    2 / 9 (22.22%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    2
    2
    2
    Skin and subcutaneous tissue disorders
    ECCHYMOSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    RASH
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    2 / 12 (16.67%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    5
    0
    0
    1
    0
    0
    0
    SKIN LESION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    0
    0
    DRUG ERUPTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    PRURITUS
         subjects affected / exposed
    1 / 4 (25.00%)
    3 / 7 (42.86%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    3
    1
    1
    0
    1
    2
    0
    0
    PURPURA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    RASH MACULO-PAPULAR
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    0
    0
    SKIN DISORDER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    ERYTHEMA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    3
    1
    0
    0
    1
    0
    0
    MUCOCUTANEOUS HAEMORRHAGE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    DRY SKIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    3 / 13 (23.08%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    4
    1
    0
    0
    BLOOD BLISTER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    NIGHT SWEATS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    PETECHIAE
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    1
    0
    HYPERHIDROSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    0
    0
    1
    RASH ERYTHEMATOUS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    DECUBITUS ULCER
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    SKIN EXFOLIATION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    0
    0
    0
    ERYTHEMA NODOSUM
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    URTICARIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    Renal and urinary disorders
    MICTURITION FREQUENCY DECREASED
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    1
    2
    0
    2
    1
    1
    0
    HAEMATURIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    2 / 21 (9.52%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    2
    1
    0
    INCONTINENCE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    COSTOVERTEBRAL ANGLE TENDERNESS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    URINARY INCONTINENCE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    3
    0
    0
    POLLAKIURIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    URINARY RETENTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    NECK PAIN
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    MUSCLE FATIGUE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    ARTHRITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    MYOSITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    JOINT SWELLING
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    PAIN IN EXTREMITY
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    1 / 21 (4.76%)
    2 / 9 (22.22%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    1
    2
    0
    MUSCLE SPASMS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    MUSCULAR WEAKNESS
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    2
    1
    0
    0
    CHONDROCALCINOSIS PYROPHOSPHATE
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    BACK PAIN
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    3 / 13 (23.08%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    3
    1
    0
    0
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    HAEMARTHROSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    ARTHRALGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    2
    3
    0
    2
    1
    1
    2
    MYALGIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    1 / 21 (4.76%)
    1 / 9 (11.11%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    1
    1
    2
    Infections and infestations
    BRONCHIOLITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    CRYPTOCOCCOSIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    FUNGAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    RECTAL ABSCESS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    INFLUENZA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    0
    HERPES VIRUS INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    ORAL HERPES
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    2
    0
    0
    PHARYNGITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    CORONAVIRUS INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    2 / 21 (9.52%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    1
    0
    0
    2
    2
    1
    0
    LIVER ABSCESS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    CLOSTRIDIUM DIFFICILE INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    0
    GASTROINTESTINAL CANDIDIASIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    CATHETER SITE CELLULITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    RASH PUSTULAR
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    ARTHRITIS BACTERIAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    ESCHERICHIA BACTERAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    SYSTEMIC CANDIDA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    TOOTH INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    CONJUNCTIVITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    PNEUMONIA FUNGAL
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    0
    PNEUMONIA
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    2 / 21 (9.52%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    2
    3
    0
    0
    PSEUDOMONAL BACTERAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    DEVICE RELATED INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    ORAL CANDIDIASIS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    1
    0
    0
    BETA HAEMOLYTIC STREPTOCOCCAL INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    CELLULITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    0
    0
    GASTROENTERITIS NOROVIRUS
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    LARYNGITIS
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    ANORECTAL INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    WOUND INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    TRICHOSPORON INFECTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    PARAINFLUENZA (URI)
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Metabolism and nutrition disorders
    HYPERGLYCAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    1 / 21 (4.76%)
    3 / 9 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    1
    0
    1
    1
    5
    0
    HYPOKALAEMIA
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 7 (14.29%)
    4 / 12 (33.33%)
    3 / 7 (42.86%)
    4 / 6 (66.67%)
    6 / 13 (46.15%)
    10 / 21 (47.62%)
    3 / 9 (33.33%)
    5 / 6 (83.33%)
         occurrences all number
    1
    1
    9
    5
    4
    11
    12
    3
    6
    DECREASED APPETITE
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 7 (28.57%)
    2 / 12 (16.67%)
    3 / 7 (42.86%)
    2 / 6 (33.33%)
    4 / 13 (30.77%)
    7 / 21 (33.33%)
    3 / 9 (33.33%)
    2 / 6 (33.33%)
         occurrences all number
    1
    2
    2
    3
    2
    4
    9
    3
    2
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    6 / 21 (28.57%)
    2 / 9 (22.22%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    1
    3
    0
    1
    8
    2
    2
    HYPERKALAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    1
    0
    0
    0
    HYPOCALCAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 7 (28.57%)
    2 / 12 (16.67%)
    3 / 7 (42.86%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
    3 / 21 (14.29%)
    2 / 9 (22.22%)
    2 / 6 (33.33%)
         occurrences all number
    0
    2
    2
    3
    1
    1
    3
    3
    2
    IRON OVERLOAD
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    FLUID RETENTION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    1 / 12 (8.33%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    MALNUTRITION
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    HYPONATRAEMIA
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 13 (15.38%)
    2 / 21 (9.52%)
    1 / 9 (11.11%)
    2 / 6 (33.33%)
         occurrences all number
    1
    0
    0
    2
    0
    2
    2
    1
    2
    HYPERPHOSPHATAEMIA
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 7 (28.57%)
    1 / 12 (8.33%)
    1 / 7 (14.29%)
    2 / 6 (33.33%)
    2 / 13 (15.38%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    1
    1
    2
    2
    1
    0
    0
    HYPERMAGNESAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    DEHYDRATION
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    1 / 21 (4.76%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    HYPOMAGNESAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    3 / 7 (42.86%)
    1 / 12 (8.33%)
    2 / 7 (28.57%)
    3 / 6 (50.00%)
    3 / 13 (23.08%)
    7 / 21 (33.33%)
    2 / 9 (22.22%)
    2 / 6 (33.33%)
         occurrences all number
    0
    3
    1
    5
    3
    4
    9
    2
    2
    FLUID OVERLOAD
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 7 (14.29%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    3 / 21 (14.29%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    3
    0
    0
    HYPOALBUMINAEMIA
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 7 (28.57%)
    0 / 12 (0.00%)
    4 / 7 (57.14%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    3 / 21 (14.29%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    1
    2
    0
    7
    0
    0
    3
    1
    0
    TUMOUR LYSIS SYNDROME
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    1
    0
    HYPERURICAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 13 (7.69%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    HYPERVOLAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    1 / 9 (11.11%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    FOLATE DEFICIENCY
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    HYPOVOLAEMIA
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    VITAMIN B12 DEFICIENCY
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 7 (0.00%)
    0 / 12 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 13 (0.00%)
    0 / 21 (0.00%)
    0 / 9 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    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
    30 Jun 2016
    Following updates were made: [1] Updates to Inclusion/Exclusion Criteria; [2] Updates to Dose Limiting Toxicity (DLT) Criteria; [3] Modification of Stratification factors used in the randomized portion of the study and [4] Addition of guidelines for the use of venetoclax and cobimetinib when co-administered with moderate CYP3A inhibitors.
    23 Nov 2016
    Following updates were made: [1] Updates to guidelines for administration of venetoclax with cobimetinib and venetoclax with idasanutlin; [2] Extension of interval for subject consent to 30 days from 21 days to allow subjects time to conduct all required assessments; [3] Updates to sample list of prohibited and cautionary medications in accordance with the FDA’s updated guidelines and [4] Updates to recommendations for prevention of tumor lysis syndrome (TLS).
    31 Jul 2017
    Following updates were made: [1] Addition of New Cohort to Arm B to explore a lower dose level of idasanutlin to obtain additional safety and tolerability data; [2] Modification of Phase 1b dose-escalation rules to a 3+3+3 design to further evaluate safety and tolerability in each dose cohort; [3] Updates to Eligibility Criteria; [4] Updates to guidelines for dose interruption and dose modification after clearance of leukemia from bone marrow; [5] Updates to the response criteria for DLT evaluation and [6] Guidance to minimize GI toxicity including instructions for mandatory prophylaxis and toxicity management were updated.
    31 Jan 2020
    Following updates were made: [1] Addition of new Secondary Efficacy Endpoints; [2] Additional detail provided to clarify the analysis of PRO and geriatric assessment data; [3] Phase II expansion portion of the study was removed; [4] A dosing schedule-optimization phase including additional cohorts in Arm B were added to optimize the venetoclax dosing schedule; [5] Eligibility criteria were amended to include objective criteria to define subjects who are not candidates for cytotoxic chemotherapy and [6] Further evaluation of Arm A would not continue.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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