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    Clinical Trial Results:
    A Phase I/II study of safety and efficacy of ribociclib (LEE011) in combination with trametinib (TMT212) in patients with metastatic or advanced solid tumors

    Summary
    EudraCT number
    2015-005019-34
    Trial protocol
    NL   BE   ES  
    Global end of trial date
    24 Sep 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    23 Sep 2020
    First version publication date
    23 Sep 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CTMT212X2106
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02703571
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.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
    24 Sep 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Sep 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of Phase Ib was to define the maximum tolerated dose (MTD) and/or the recommended Phase II regimen (RP2R) of ribociclib and trametinib in patients with solid tumors. The Phase II part was not pursued, and the study was closed after completion of the Phase Ib part of the study.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    29 Jun 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 13
    Country: Number of subjects enrolled
    Canada: 10
    Country: Number of subjects enrolled
    Germany: 5
    Country: Number of subjects enrolled
    Netherlands: 10
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    United States: 46
    Country: Number of subjects enrolled
    Australia: 7
    Worldwide total number of subjects
    95
    EEA total number of subjects
    32
    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)
    66
    From 65 to 84 years
    29
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Participants took part in 15 investigative sites in 7 countries from 29-Jun-2016 to 14-Mar-2019

    Pre-assignment
    Screening details
    Subjects with advanced or metastatic solid tumors independently of the RAS mutation status were screened for eligibility during the 28 days prior to starting study treatment on Cycle 1 Day 1. The eligibility assessments were performed and ensured that all inclusion and exclusion were satisfied.

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

    Arms
    Arm title
    TMT212+LEE011
    Arm description
    Phase Ib part: Patients with advanced or metastatic solid tumors participating in the Phase I part received combination treatment with ribociclib (projected dose levels: 0.5 mg, 1 mg, 1.5 mg and 2 mg) and trametinib (projected dose levels: 200 mg, 300 mg, 400 mg, 500 mg and 600 mg) at different dosing regimens. Phase II part: Patients with advanced or metastatic pancreatic adenocarcinoma who have failed at least one prior systemic treatment and patients with advanced or metastatic KRAS mutant colorectal carcinoma who have failed at least two prior lines of treatment.
    Arm type
    Experimental

    Investigational medicinal product name
    Ribociclib
    Investigational medicinal product code
    LEE011
    Other name
    Pharmaceutical forms
    Tablet, Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    During the Phase I part, ribociclib was administered orally and escalated from 200 to 600mg at different dosing schedules: 1) once daily on days 1 to 21 of a 28 days cycle; 2) once daily on days 8 to 21 of a 21-day cycle (Schedule 1); and 3) once daily on days 1 to 14 of a 21-day cycle (Schedule 2).

    Investigational medicinal product name
    Trametinib
    Investigational medicinal product code
    TMT212
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    During the Phase I part, trametinib 0.5, 1, 1.5 or 2 mg was administered orally at different dosing schedules: 1) once daily on days 1 to 21 of a 28-day cycle; 2) once daily on days 1 to 14 of a 21-day cycle (Schedule 1 and Schedule 2)

    Number of subjects in period 1
    TMT212+LEE011
    Started
    95
    Full analysis set
    95
    Safety set
    95
    Dose determining set
    79
    Completed
    0
    Not completed
    95
         Physician decision
    8
         Adverse event, serious fatal
    1
         Adverse event, non-fatal
    14
         Disease progression
    55
         Sponsor decision
    1
         Lost to follow-up
    1
         Subject/guardian decision
    15

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall study
    Reporting group description
    Patients with advanced or metastatic solid tumors participating in the Phase I part received combination treatment with ribociclib (projected dose levels: 0.5 mg, 1 mg, 1.5 mg and 2 mg) and trametinib (projected dose levels: 200 mg, 300 mg, 400 mg, 500 mg and 600 mg) at different dosing regimens. Phase II part of the study was not conducted

    Reporting group values
    Overall study Total
    Number of subjects
    95 95
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    66 66
        From 65-84 years
    29 29
        85 years and over
    0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    58.0 ± 9.89 -
    Sex: Female, Male
    Units: Participants
        Female
    46 46
        Male
    49 49
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    5 5
        Black
    2 2
        Caucasian
    84 84
        Pacific islander
    1 1
        Unknown
    3 3

    End points

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    End points reporting groups
    Reporting group title
    TMT212+LEE011
    Reporting group description
    Phase Ib part: Patients with advanced or metastatic solid tumors participating in the Phase I part received combination treatment with ribociclib (projected dose levels: 0.5 mg, 1 mg, 1.5 mg and 2 mg) and trametinib (projected dose levels: 200 mg, 300 mg, 400 mg, 500 mg and 600 mg) at different dosing regimens. Phase II part: Patients with advanced or metastatic pancreatic adenocarcinoma who have failed at least one prior systemic treatment and patients with advanced or metastatic KRAS mutant colorectal carcinoma who have failed at least two prior lines of treatment.

    Primary: Phase Ib: Number of participants with dose limiting toxicities (DLTs)

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    End point title
    Phase Ib: Number of participants with dose limiting toxicities (DLTs) [1]
    End point description
    Phase Ib part: Incidence of DLTs during the first 21 days of therapy. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with ribociclib and trametinib and meets any of the criteria described in the protocol.
    End point type
    Primary
    End point timeframe
    21-day cycle one of treatment
    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 were planned for this endpoint
    End point values
    TMT212+LEE011
    Number of subjects analysed
    79
    Units: Participants
    12
    No statistical analyses for this end point

    Primary: Phase II: Objective Response Rate (ORR)

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    End point title
    Phase II: Objective Response Rate (ORR) [2]
    End point description
    Phase II part: ORR is defined as the proportion of patients with a best overall confirmed complete response (CR) or partial response (PR), as assessed per RECIST 1.1 by investigator assessment.
    End point type
    Primary
    End point timeframe
    Until progression of disease up to 1 year
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were planned for this endpoint
    End point values
    TMT212+LEE011
    Number of subjects analysed
    0 [3]
    Units: Percentage of participants
        number (confidence interval 95%)
    ( to )
    Notes
    [3] - Phase 2 was not initiated; no data was collected.
    No statistical analyses for this end point

    Secondary: Phase Ib: Progression disease rate

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    End point title
    Phase Ib: Progression disease rate
    End point description
    Phase Ib part: Progression disease rate defined as the proportion of patients with a progression disease as assessed per RECIST 1.1 by investigator assessment.
    End point type
    Secondary
    End point timeframe
    Until progression of disease, up to approximately 2 years
    End point values
    TMT212+LEE011
    Number of subjects analysed
    95
    Units: Percentage of Participants
        number (confidence interval 95%)
    44.2 (34.0 to 54.8)
    No statistical analyses for this end point

    Secondary: Phase Ib: Progression free survival (PFS)

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    End point title
    Phase Ib: Progression free survival (PFS)
    End point description
    Phase Ib part: PFS is defined as the time from the date of the first dose of study drug to the date of first documented disease progression per RECIST 1.1 and investigator assessment or death due to any cause.
    End point type
    Secondary
    End point timeframe
    Until progression of disease or death, up to approximately 2 years
    End point values
    TMT212+LEE011
    Number of subjects analysed
    95
    Units: Months
        median (confidence interval 95%)
    2.6 (1.8 to 3.2)
    No statistical analyses for this end point

    Secondary: Phase II: Duration of response (DOR)

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    End point title
    Phase II: Duration of response (DOR)
    End point description
    Phase II part: Among patients with a confirmed response (PR or CR) per RECIST 1.1, DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause.
    End point type
    Secondary
    End point timeframe
    From first documented response until progression of disease or death, up to 1 year
    End point values
    TMT212+LEE011
    Number of subjects analysed
    0 [4]
    Units: Months
        arithmetic mean (confidence interval 95%)
    ( to )
    Notes
    [4] - Phase 2 was not initiated; no data was collected.
    No statistical analyses for this end point

    Secondary: Phase II: Time to response

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    End point title
    Phase II: Time to response
    End point description
    Phase II part:Time to overall response of CR or PR (TTR) is defined as the time from start of study drug to first documented response (CR or PR, which must be confirmed subsequently) for patients with a confirmed CR or PR. Phase 2 was not initiated; no data was collected.
    End point type
    Secondary
    End point timeframe
    From start of study drug to first documented response, up to 1 year
    End point values
    TMT212+LEE011
    Number of subjects analysed
    0 [5]
    Units: Months
        arithmetic mean (confidence interval 95%)
    ( to )
    Notes
    [5] - Phase 2 was not initiated; no data was collected.
    No statistical analyses for this end point

    Secondary: Phase II: Disease Control Rate (DCR)

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    End point title
    Phase II: Disease Control Rate (DCR)
    End point description
    Phase II part: DCR is defined as the proportion of patients with best overall response of CR, PR, or SD per RECIST 1.1. Phase 2 was not initiated; no data was collected.
    End point type
    Secondary
    End point timeframe
    Until progression of disease up to 1 year
    End point values
    TMT212+LEE011
    Number of subjects analysed
    0 [6]
    Units: Percentage of Participants
        number (confidence interval 95%)
    ( to )
    Notes
    [6] - Phase 2 was not initiated; no data was collected.
    No statistical analyses for this end point

    Secondary: Phase II: Progression Free Survival (PFS)

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    End point title
    Phase II: Progression Free Survival (PFS)
    End point description
    Phase II part: PFS is defined as the time from the date of the first dose of study drug to the date of first documented disease progression per RECIST 1.1 and investigator assessment or death due to any cause. Phase 2 was not initiated; no data was collected.
    End point type
    Secondary
    End point timeframe
    Until progression of disease or death, up to 1 year
    End point values
    TMT212+LEE011
    Number of subjects analysed
    0 [7]
    Units: Months
        median (confidence interval 95%)
    ( to )
    Notes
    [7] - Phase 2 was not initiated; no data was collected.
    No statistical analyses for this end point

    Secondary: Phase II: Overall Survival (OS)

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    End point title
    Phase II: Overall Survival (OS)
    End point description
    Phase II part: OS is defined as the time from the date of first dose of study drug to the date of death due to any cause. Phase 2 was not initiated; no data was collected.
    End point type
    Secondary
    End point timeframe
    Up to 1 year
    End point values
    TMT212+LEE011
    Number of subjects analysed
    0 [8]
    Units: Months
        median (confidence interval 95%)
    ( to )
    Notes
    [8] - Phase 2 was not initiated; no data was collected.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 25.53 months.
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Cohort 0: LEE011 200mg 21 on/7 off + TMT212 2 mg QD
    Reporting group description
    2 mg TMT212 administered once daily on Days 1-28 and 200 mg LEE011 administered once daily on Days 1-21 followed by a 7-day break of a 28-day cycle

    Reporting group title
    Cohort 1: TMT212 1.5 mg QD + LEE011 200 mg QD - Schedule 1
    Reporting group description
    1.5 mg TMT212 administered once daily on Days 1-14 and 200 mg LEE011 administered once daily on Days 8-21 of a 21-day cycle.

    Reporting group title
    Cohort 2a: TMT212 2 mg QD + LEE011 200 mg QD- Schedule 1
    Reporting group description
    2 mg TMT212 administered once daily on Days 1-14 and 200 mg LEE011 administered once daily on Days 8-21 of a 21-day cycle

    Reporting group title
    Cohort 2b: TMT212 1.5 mg QD + LEE011 300 mg QD- Schedule 1
    Reporting group description
    1.5 mg TMT212 administered once daily on Days 1-14 and 300 mg LEE011 administered once daily on Days 8-21 of a 21-day cycle

    Reporting group title
    Cohort 3a: TMT212 2 mg QD + LEE011 300 mg QD- Schedule 1
    Reporting group description
    2 mg TMT212 administered once daily on Days 1-14 and 300 mg LEE011 administered once daily on Days 8-21 of a 21-day cycle

    Reporting group title
    Cohort 3b: TMT212 1.5 mg QD + LEE011 400 mg QD - Schedule 1
    Reporting group description
    1.5 mg TMT212 administered once daily on Days 1-14 and 400 mg LEE011 administered once daily on Days 8-21 of a 21-day cycle

    Reporting group title
    Cohort 4a: TMT212 2 mg QD + LEE011 400 mg QD - Schedule 1
    Reporting group description
    2 mg TMT212 administered once daily on Days 1-14 and 400 mg LEE011 administered once daily on Days 8-21 of a 21-day cycle

    Reporting group title
    Cohort 4a*: TMT212 2 mg QD + LEE011 400 mg QD- Schedule 2
    Reporting group description
    2 mg TMT212 administered once daily on Days 1-14 and LEE011 administered once daily on Days 1-14 of a 21-day cycle

    Reporting group title
    Cohort 5a: TMT212 2 mg QD + LEE011 500 mg QD- Schedule 1
    Reporting group description
    2 mg TMT212 administered once daily on Days 1-14 and 500 mg LEE011 administered once daily on Days 8-21 of a 21-day cycle

    Reporting group title
    Cohort Xa: TMT212 1 mg QD + LEE011 300 mg QD- Schedule 1
    Reporting group description
    1 mg TMT212 administered once daily on Days 1-14 and 300 mg LEE011 administered once daily on Days 8-21 of a 21-day cycle

    Reporting group title
    Cohort Xb: TMT212 1 mg QD + LEE011 400 mg QD- Schedule 1
    Reporting group description
    1 mg TMT212 administered once daily on Days 1-14 and 400 mg LEE011 administered once daily on Days 8-21 of a 21-day cycle

    Reporting group title
    All Subjects
    Reporting group description
    All subjects who received at least one dose of either study drug in the Phase I part of the study

    Serious adverse events
    Cohort 0: LEE011 200mg 21 on/7 off + TMT212 2 mg QD Cohort 1: TMT212 1.5 mg QD + LEE011 200 mg QD - Schedule 1 Cohort 2a: TMT212 2 mg QD + LEE011 200 mg QD- Schedule 1 Cohort 2b: TMT212 1.5 mg QD + LEE011 300 mg QD- Schedule 1 Cohort 3a: TMT212 2 mg QD + LEE011 300 mg QD- Schedule 1 Cohort 3b: TMT212 1.5 mg QD + LEE011 400 mg QD - Schedule 1 Cohort 4a: TMT212 2 mg QD + LEE011 400 mg QD - Schedule 1 Cohort 4a*: TMT212 2 mg QD + LEE011 400 mg QD- Schedule 2 Cohort 5a: TMT212 2 mg QD + LEE011 500 mg QD- Schedule 1 Cohort Xa: TMT212 1 mg QD + LEE011 300 mg QD- Schedule 1 Cohort Xb: TMT212 1 mg QD + LEE011 400 mg QD- Schedule 1 All Subjects
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 5 (40.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    5 / 12 (41.67%)
    4 / 12 (33.33%)
    6 / 10 (60.00%)
    6 / 9 (66.67%)
    5 / 10 (50.00%)
    2 / 10 (20.00%)
    6 / 9 (66.67%)
    40 / 95 (42.11%)
         number of deaths (all causes)
    1
    1
    0
    1
    1
    0
    1
    1
    0
    0
    2
    8
         number of deaths resulting from adverse events
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    General disorders and administration site conditions
    Administration site extravasation
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Occult blood positive
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary arterial hypertension
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral ischaemia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Presyncope
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal vein occlusion
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    3 / 95 (3.16%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    1 / 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
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    2 / 95 (2.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Gastrointestinal perforation
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    2 / 95 (2.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 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
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    3 / 95 (3.16%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    6 / 95 (6.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    2 / 95 (2.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Groin pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal sepsis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    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
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Biliary tract infection
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash pustular
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cohort 0: LEE011 200mg 21 on/7 off + TMT212 2 mg QD Cohort 1: TMT212 1.5 mg QD + LEE011 200 mg QD - Schedule 1 Cohort 2a: TMT212 2 mg QD + LEE011 200 mg QD- Schedule 1 Cohort 2b: TMT212 1.5 mg QD + LEE011 300 mg QD- Schedule 1 Cohort 3a: TMT212 2 mg QD + LEE011 300 mg QD- Schedule 1 Cohort 3b: TMT212 1.5 mg QD + LEE011 400 mg QD - Schedule 1 Cohort 4a: TMT212 2 mg QD + LEE011 400 mg QD - Schedule 1 Cohort 4a*: TMT212 2 mg QD + LEE011 400 mg QD- Schedule 2 Cohort 5a: TMT212 2 mg QD + LEE011 500 mg QD- Schedule 1 Cohort Xa: TMT212 1 mg QD + LEE011 300 mg QD- Schedule 1 Cohort Xb: TMT212 1 mg QD + LEE011 400 mg QD- Schedule 1 All Subjects
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5 / 5 (100.00%)
    7 / 7 (100.00%)
    6 / 6 (100.00%)
    5 / 5 (100.00%)
    12 / 12 (100.00%)
    12 / 12 (100.00%)
    10 / 10 (100.00%)
    8 / 9 (88.89%)
    10 / 10 (100.00%)
    10 / 10 (100.00%)
    9 / 9 (100.00%)
    94 / 95 (98.95%)
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Embolism
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Hypertension
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    3 / 10 (30.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    11 / 95 (11.58%)
         occurrences all number
    1
    2
    0
    0
    2
    0
    3
    0
    2
    1
    1
    12
    Hypotension
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    3 / 95 (3.16%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    3
    Lymphoedema
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    2
    Vascular rupture
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pyogenic granuloma
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Tumour pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
    2 / 12 (16.67%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    4 / 95 (4.21%)
         occurrences all number
    0
    0
    1
    1
    0
    2
    0
    0
    0
    0
    0
    4
    Immune system disorders
    Contrast media reaction
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    2
    Immune system disorder
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Seasonal allergy
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    8 / 95 (8.42%)
         occurrences all number
    0
    2
    0
    0
    1
    1
    1
    3
    1
    1
    0
    10
    Device related thrombosis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Face oedema
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Fatigue
         subjects affected / exposed
    3 / 5 (60.00%)
    5 / 7 (71.43%)
    3 / 6 (50.00%)
    4 / 5 (80.00%)
    8 / 12 (66.67%)
    7 / 12 (58.33%)
    6 / 10 (60.00%)
    4 / 9 (44.44%)
    5 / 10 (50.00%)
    5 / 10 (50.00%)
    4 / 9 (44.44%)
    54 / 95 (56.84%)
         occurrences all number
    3
    5
    3
    4
    9
    7
    7
    5
    6
    5
    4
    58
    Gait disturbance
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Malaise
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    3
    Oedema
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Oedema peripheral
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    5 / 12 (41.67%)
    5 / 12 (41.67%)
    5 / 10 (50.00%)
    3 / 9 (33.33%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    26 / 95 (27.37%)
         occurrences all number
    0
    1
    4
    1
    7
    6
    6
    3
    1
    1
    2
    32
    Pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Peripheral swelling
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    2
    Pyrexia
         subjects affected / exposed
    1 / 5 (20.00%)
    3 / 7 (42.86%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    4 / 12 (33.33%)
    3 / 12 (25.00%)
    2 / 10 (20.00%)
    3 / 9 (33.33%)
    3 / 10 (30.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    22 / 95 (23.16%)
         occurrences all number
    1
    5
    1
    1
    4
    3
    2
    3
    3
    1
    0
    24
    Secretion discharge
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Suprapubic pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Swelling face
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Temperature intolerance
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Xerosis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    2
    Bruxism
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Confusional state
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    2
    Depression
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    3 / 95 (3.16%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    1
    0
    0
    3
    Insomnia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    2
    Mental status changes
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Sleep disorder
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Breast pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Pelvic pain
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Scrotal pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Uterine pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Vulvovaginal pruritus
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Avulsion fracture
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Fracture
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Thermal burn
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Wrist fracture
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    2
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    2 / 12 (16.67%)
    2 / 12 (16.67%)
    2 / 10 (20.00%)
    4 / 9 (44.44%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    19 / 95 (20.00%)
         occurrences all number
    2
    0
    3
    3
    2
    3
    2
    12
    3
    0
    2
    32
    Amylase increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    7 / 95 (7.37%)
         occurrences all number
    0
    0
    2
    0
    0
    1
    0
    3
    2
    1
    4
    13
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 7 (14.29%)
    4 / 6 (66.67%)
    4 / 5 (80.00%)
    5 / 12 (41.67%)
    4 / 12 (33.33%)
    7 / 10 (70.00%)
    5 / 9 (55.56%)
    4 / 10 (40.00%)
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    38 / 95 (40.00%)
         occurrences all number
    2
    2
    5
    5
    6
    4
    8
    8
    6
    1
    2
    49
    Bilirubin conjugated increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 5 (0.00%)
    3 / 7 (42.86%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    2 / 12 (16.67%)
    1 / 12 (8.33%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    15 / 95 (15.79%)
         occurrences all number
    0
    3
    2
    2
    4
    1
    1
    0
    3
    0
    4
    20
    Blood bilirubin increased
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    6 / 95 (6.32%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    3
    0
    0
    1
    0
    7
    Blood creatine increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    2
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 5 (40.00%)
    3 / 7 (42.86%)
    3 / 6 (50.00%)
    1 / 5 (20.00%)
    6 / 12 (50.00%)
    6 / 12 (50.00%)
    4 / 10 (40.00%)
    4 / 9 (44.44%)
    5 / 10 (50.00%)
    0 / 10 (0.00%)
    3 / 9 (33.33%)
    37 / 95 (38.95%)
         occurrences all number
    2
    3
    4
    1
    10
    6
    6
    8
    7
    0
    3
    50
    Blood creatinine decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    3 / 6 (50.00%)
    0 / 5 (0.00%)
    2 / 12 (16.67%)
    2 / 12 (16.67%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    11 / 95 (11.58%)
         occurrences all number
    0
    0
    3
    0
    2
    3
    0
    3
    3
    2
    0
    16
    Blood urea increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    C-reactive protein increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Ejection fraction decreased
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    4 / 95 (4.21%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    1
    1
    0
    4
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    8 / 95 (8.42%)
         occurrences all number
    1
    1
    2
    1
    1
    1
    0
    1
    0
    0
    1
    9
    International normalised ratio increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Lipase increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    9 / 95 (9.47%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    1
    6
    3
    0
    4
    17
    Liver function test increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 7 (28.57%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    4 / 95 (4.21%)
         occurrences all number
    0
    2
    1
    0
    0
    0
    0
    0
    1
    0
    0
    4
    Monocyte count decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    4 / 12 (33.33%)
    0 / 12 (0.00%)
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    10 / 95 (10.53%)
         occurrences all number
    0
    0
    2
    0
    6
    0
    3
    1
    1
    0
    2
    15
    Neutrophil count increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Platelet count decreased
         subjects affected / exposed
    2 / 5 (40.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    2 / 12 (16.67%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    2 / 10 (20.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    10 / 95 (10.53%)
         occurrences all number
    2
    0
    0
    0
    2
    2
    1
    1
    2
    1
    0
    11
    Weight decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    7 / 95 (7.37%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    1
    1
    0
    1
    2
    7
    Weight increased
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    3 / 12 (25.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    3 / 10 (30.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    9 / 95 (9.47%)
         occurrences all number
    0
    2
    0
    0
    0
    4
    0
    2
    4
    0
    1
    13
    Cardiac disorders
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Bradycardia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Mitral valve thickening
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Sinus bradycardia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Tachycardia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    1
    0
    0
    3
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Aphonia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Cough
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    8 / 95 (8.42%)
         occurrences all number
    1
    1
    1
    0
    1
    1
    0
    2
    0
    0
    2
    9
    Dysphonia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    4 / 95 (4.21%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    1
    1
    0
    0
    0
    4
    Dyspnoea
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    3 / 12 (25.00%)
    1 / 12 (8.33%)
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    16 / 95 (16.84%)
         occurrences all number
    0
    1
    2
    1
    3
    1
    2
    2
    1
    1
    2
    16
    Dyspnoea at rest
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Dyspnoea exertional
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Epistaxis
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    4 / 95 (4.21%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    0
    0
    1
    0
    0
    4
    Haemoptysis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    2
    Increased upper airway secretion
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Nasal congestion
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    2
    Oropharyngeal pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 12 (16.67%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    3 / 95 (3.16%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    1
    0
    0
    0
    3
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Pleural effusion
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    2
    Pleuritic pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Pneumonitis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Productive cough
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    3 / 95 (3.16%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    3
    Rhinorrhoea
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    2
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 5 (60.00%)
    2 / 7 (28.57%)
    3 / 6 (50.00%)
    2 / 5 (40.00%)
    8 / 12 (66.67%)
    7 / 12 (58.33%)
    3 / 10 (30.00%)
    5 / 9 (55.56%)
    3 / 10 (30.00%)
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    40 / 95 (42.11%)
         occurrences all number
    4
    3
    3
    3
    9
    9
    3
    8
    3
    4
    3
    52
    Leukopenia
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    5 / 95 (5.26%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    1
    1
    3
    0
    7
    Lymphopenia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    0
    2
    Neutropenia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    3 / 12 (25.00%)
    1 / 12 (8.33%)
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    3 / 10 (30.00%)
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    14 / 95 (14.74%)
         occurrences all number
    0
    1
    0
    0
    5
    2
    1
    3
    6
    2
    1
    21
    Thrombocytopenia
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 12 (16.67%)
    0 / 12 (0.00%)
    2 / 10 (20.00%)
    3 / 9 (33.33%)
    4 / 10 (40.00%)
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    15 / 95 (15.79%)
         occurrences all number
    2
    0
    0
    0
    2
    0
    2
    4
    7
    1
    2
    20
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Balance disorder
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Dizziness
         subjects affected / exposed
    1 / 5 (20.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    1 / 12 (8.33%)
    2 / 12 (16.67%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    11 / 95 (11.58%)
         occurrences all number
    1
    3
    0
    2
    1
    2
    0
    2
    1
    1
    0
    13
    Dysgeusia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    7 / 95 (7.37%)
         occurrences all number
    0
    0
    2
    1
    1
    0
    2
    0
    2
    0
    1
    9
    Headache
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    2 / 12 (16.67%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    5 / 95 (5.26%)
         occurrences all number
    0
    0
    0
    2
    2
    1
    0
    0
    0
    1
    0
    6
    Hyperaesthesia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    2
    Hypoaesthesia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    2
    0
    0
    4
    Neuropathy peripheral
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    3 / 12 (25.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    4 / 95 (4.21%)
         occurrences all number
    0
    0
    0
    0
    3
    3
    0
    0
    0
    0
    0
    6
    Paraesthesia
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    2
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    3 / 95 (3.16%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    1
    0
    0
    0
    0
    4
    Seizure
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    2
    Somnolence
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Syncope
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    2
    Taste disorder
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    2
    Tongue paralysis
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Transient ischaemic attack
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Eye disorders
    Chorioretinopathy
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Dry eye
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    3 / 95 (3.16%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    1
    0
    0
    0
    3
    Eye irritation
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Eye pain
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Eye swelling
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Periorbital oedema
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Retinal detachment
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Retinal disorder
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    2
    Retinal exudates
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Subretinal fluid
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Vision blurred
         subjects affected / exposed
    0 / 5 (0.00%)
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    3 / 95 (3.16%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    1
    0
    0
    0
    0
    3
    Visual impairment
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    2
    Vitreous floaters
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    2
    Ear and labyrinth disorders
    Ear congestion
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Tinnitus
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Vertigo
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    3 / 95 (3.16%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    2
    0
    0
    0
    4
    Abdominal distension
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    Abdominal pain
         subjects affected / exposed
    1 / 5 (20.00%)
    3 / 7 (42.86%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    1 / 10 (10.00%)
    3 / 9 (33.33%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    2 / 9 (22.22%)
    13 / 95 (13.68%)
         occurrences all number
    1
    3
    0
    1
    0
    1
    1
    4
    0
    2
    2
    15
    Abdominal pain lower
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 5 (20.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    3 / 95 (3.16%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    3
    Anal incontinence
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Aphthous ulcer
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Ascites
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Constipation
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    1 / 12 (8.33%)
    2 / 12 (16.67%)
    3 / 10 (30.00%)
    2 / 9 (22.22%)
    0 / 10 (0.00%)
    2 / 10 (20.00%)
    2 / 9 (22.22%)
    17 / 95 (17.89%)
         occurrences all number
    0
    2
    2
    2
    1
    2
    3
    2
    0
    2
    2
    18
    Diarrhoea
         subjects affected / exposed
    3 / 5 (60.00%)
    5 / 7 (71.43%)
    2 / 6 (33.33%)
    3 / 5 (60.00%)
    6 / 12 (50.00%)
    7 / 12 (58.33%)
    4 / 10 (40.00%)
    5 / 9 (55.56%)
    9 / 10 (90.00%)
    1 / 10 (10.00%)
    5 / 9 (55.56%)
    50 / 95 (52.63%)
         occurrences all number
    3
    12
    6
    3
    6
    10
    6
    6
    13
    1
    6
    72
    Dry mouth
         subjects affected / exposed
    1 / 5 (20.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    2 / 12 (16.67%)
    0 / 12 (0.00%)
    3 / 10 (30.00%)
    2 / 9 (22.22%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    10 / 95 (10.53%)
         occurrences all number
    1
    0
    1
    0
    2
    0
    3
    3
    1
    0
    0
    11
    Duodenal ulcer
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Dyspepsia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    4 / 95 (4.21%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    1
    2
    5
    Dysphagia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Flatulence
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    4 / 95 (4.21%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    1
    0
    0
    1
    4
    Haemorrhoids
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Intra-abdominal haematoma
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Lip dry
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Lip pain
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Lip swelling
         subjects affected / exposed
    0 / 5 (0.00%)
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    2
    Mouth ulceration
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Nausea
         subjects affected / exposed
    0 / 5 (0.00%)
    3 / 7 (42.86%)
    4 / 6 (66.67%)
    3 / 5 (60.00%)
    7 / 12 (58.33%)
    7 / 12 (58.33%)
    3 / 10 (30.00%)
    3 / 9 (33.33%)
    5 / 10 (50.00%)
    4 / 10 (40.00%)
    5 / 9 (55.56%)
    44 / 95 (46.32%)
         occurrences all number
    0
    6
    5
    3
    10
    8
    4
    5
    6
    5
    6
    58
    Oesophageal discomfort
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Oesophagitis
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    2
    Oral discomfort
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Proctalgia
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 95 (1.05%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Rectal haemorrhage
         subjects affected / exposed
    0 / 5 (0.00%)
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    2 / 95 (2.11%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0