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    Clinical Trial Results:
    A Multicenter, Open-label, Single-arm, Extension Study to Assess Long-term Safety of Evolocumab Therapy in Subjects With Clinically Evident Cardiovascular Disease in Selected European Countries

    Summary
    EudraCT number
    		 2016-004066-26
    Trial protocol
    		 DE   SE   DK   PT   BE   IT  
    Global end of trial date
    04 Mar 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    05 Jan 2023
    First version publication date
    05 Jan 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20160250
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03080935
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States,
    Public contact
    Amgen (EUROPE) GmbH, IHQ Medical Info-Clinical Trials, MedInfoInternational@amgen.com
    Scientific contact
    Amgen (EUROPE) GmbH, IHQ Medical Info-Clinical Trials, MedInfoInternational@amgen.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
    04 Mar 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Mar 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this trial was to describe the safety and tolerability of long-term administration of evolocumab.
    Protection of trial subjects
    This study was conducted in accordance with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Mar 2017
    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: 158
    Country: Number of subjects enrolled
    Denmark: 354
    Country: Number of subjects enrolled
    France: 178
    Country: Number of subjects enrolled
    Germany: 292
    Country: Number of subjects enrolled
    Italy: 198
    Country: Number of subjects enrolled
    Portugal: 191
    Country: Number of subjects enrolled
    Sweden: 229
    Worldwide total number of subjects
    1600
    EEA total number of subjects
    1600
    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)
    823
    From 65 to 84 years
    776
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was an open-label extension of study 20110118 (NCT01764633). Eligible participants were enrolled after the completion of the 20110118 study. Participants were enrolled at 86 centers in Belgium, Germany, Denmark, France, Italy, Portugal, and Sweden.

    Pre-assignment
    Screening details
    		 Participants were enrolled from 13 March 2017 to 04 March 2022. A total of 1600 participants were enrolled and 1599 of those participants received study drug.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo in Parent Study
    Arm description
    		 Participants in the parent study who received placebo subcutaneous injections either Q2W or QM, and received evolocumab 140 mg every 2 weeks Q2W or 420 mg monthly QM in the open label extension, according to the participant's preference.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Evolocumab
    Investigational medicinal product code
    Other name
    Repatha
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Evolocumab was administered by subcutaneous injections either 140 mg every 2 weeks or 420 mg monthly, according to the participant's preference.

    Arm title
    		 Evolocumab in Parent Study
    Arm description
    		 Participants in the parent study who received evolocumab either Q2W or QM, and received evolocumab 140 mg Q2W or 420 mg QM in the open label extension according to the participants preference.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Evolocumab
    Investigational medicinal product code
    Other name
    Repatha
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Evolocumab was administered by subcutaneous injections either 140 mg every 2 weeks or 420 mg monthly, according to the participant's preference.

    Number of subjects in period 1
    		Placebo in Parent Study Evolocumab in Parent Study
    Started
    745
    855
    Completed
    695
    786
    Not completed
    50
    69
         Adverse event, serious fatal
    34
    50
         Consent withdrawn by subject
    11
    15
         Lost to follow-up
    5
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo in Parent Study
    Reporting group description
    		 Participants in the parent study who received placebo subcutaneous injections either Q2W or QM, and received evolocumab 140 mg every 2 weeks Q2W or 420 mg monthly QM in the open label extension, according to the participant's preference.

    Reporting group title
    Evolocumab in Parent Study
    Reporting group description
    		 Participants in the parent study who received evolocumab either Q2W or QM, and received evolocumab 140 mg Q2W or 420 mg QM in the open label extension according to the participants preference.

    Reporting group values
    		 Placebo in Parent Study Evolocumab in Parent Study Total
    Number of subjects
    		 745 855 1600
    Age Categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 378 444 822
        From 65-84 years
    		 367 409 776
        85 years and over
    		 0 1 1
        Unknown
    		 0 1 1
    Gender Categorical
    Units: Subjects
        Female
    		 138 151 289
        Male
    		 607 703 1310
        Unknown
    		 0 1 1
    Ethnicity
    Units: Subjects
        Hispanic/Latino
    		 17 24 41
        Not Hispanic/Latino
    		 728 830 1558
        Unknown
    		 0 1 1
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 0 2 2
        Black or African American
    		 1 0 1
        Native Hawaiian or Other Pacific Islander
    		 0 2 2
        White
    		 706 797 1503
        Multiple
    		 0 0 0
        Other
    		 38 53 91
        Unknown
    		 0 1 1

    End points

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    End points reporting groups
    Reporting group title
    Placebo in Parent Study
    Reporting group description
    		 Participants in the parent study who received placebo subcutaneous injections either Q2W or QM, and received evolocumab 140 mg every 2 weeks Q2W or 420 mg monthly QM in the open label extension, according to the participant's preference.

    Reporting group title
    Evolocumab in Parent Study
    Reporting group description
    		 Participants in the parent study who received evolocumab either Q2W or QM, and received evolocumab 140 mg Q2W or 420 mg QM in the open label extension according to the participants preference.

    Primary: Number of Participants Who Experienced an Adverse Event (AE)

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    End point title
    		 Number of Participants Who Experienced an Adverse Event (AE) [1]
    End point description
    All adverse event summaries for the primary analysis of the primary endpoint (OLE study period only) included all treatment-emergent events reported on the Event electronic case report form (eCRF), including CEC positively reviewed events and disease-related events.
    End point type
    Primary
    End point timeframe
    Up to 5 years
    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 analysis was planned for this endpoint.
    End point values
    		 Placebo in Parent Study Evolocumab in Parent Study
    Number of subjects analysed
    745
    854
    Units: Participants
        Number of Participants Who Experienced an AE
    686
    810
    No statistical analyses for this end point

    Secondary: Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit

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    End point title
    		 Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260
    End point values
    		 Placebo in Parent Study Evolocumab in Parent Study
    Number of subjects analysed
    745
    854
    Units: Percent Change
    arithmetic mean (standard deviation)
        Week 12
    -66.32 ( 26.88 )
    -67.24 ( 25.23 )
        Week 24
    -66.48 ( 27.52 )
    -66.47 ( 28.11 )
        Week 48
    -62.61 ( 26.60 )
    -63.45 ( 26.03 )
        Week 72
    -65.58 ( 28.13 )
    -65.33 ( 28.42 )
        Week 96
    -64.58 ( 27.01 )
    -63.43 ( 28.80 )
        Week 120
    -64.26 ( 28.31 )
    -63.10 ( 29.56 )
        Week 144
    -66.79 ( 29.22 )
    -65.13 ( 31.96 )
        Week 168
    -65.28 ( 27.55 )
    -63.55 ( 29.60 )
        Week 192
    -65.02 ( 27.93 )
    -62.46 ( 26.39 )
        Week 216
    -64.92 ( 27.93 )
    -62.46 ( 28.32 )
        Week 260
    -66.45 ( 29.84 )
    -64.72 ( 29.50 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Achieved an LDL-C level < 40 mg/dL

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    End point title
    		 Percentage of Participants who Achieved an LDL-C level < 40 mg/dL
    End point description
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260
    End point values
    		 Placebo in Parent Study Evolocumab in Parent Study
    Number of subjects analysed
    745
    854
    Units: Percentage of Participants
    number (confidence interval 95%)
        Week 12
    72.8 (69.4 to 75.9)
    72.5 (69.4 to 75.4)
        Week 24
    72.9 (69.5 to 76.0)
    73.4 (70.3 to 76.2)
        Week 48
    66.5 (63.0 to 69.9)
    68.0 (64.8 to 71.1)
        Week 72
    73.2 (69.8 to 76.3)
    72.3 (69.1 to 75.2)
        Week 96
    71.1 (67.6 to 74.3)
    69.2 (65.9 to 72.3)
        Week 120
    70.9 (67.5 to 74.2)
    68.6 (65.3 to 71.8)
        Week 144
    75.3 (71.2 to 78.9)
    72.2 (68.5 to 75.7)
        Week 168
    72.3 (68.8 to 75.6)
    69.3 (65.9 to 72.5)
        Week 192
    71.6 (67.9 to 74.9)
    66.3 (62.8 to 69.7)
        Week 216
    72.1 (68.6 to 75.4)
    67.3 (63.9 to 70.6)
        Week 260
    76.1 (71.6 to 80.2)
    68.8 (64.2 to 73.0)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 5 years
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Placebo in Parent Study
    Reporting group description
    		 Participants in the parent study who received placebo subcutaneous injections either Q2W or QM, and received evolocumab 140 mg every 2 weeks Q2W or 420 mg monthly QM in the open label extension, according to the participant's preference.

    Reporting group title
    Evolocumab in Parent Study
    Reporting group description
    		 Participants in the parent study who received evolocumab either Q2W or QM, and received evolocumab 140 mg Q2W or 420 mg QM in the open label extension according to the participants preference.

    Serious adverse events
    		 Placebo in Parent Study Evolocumab in Parent Study
    Total subjects affected by serious adverse events
         subjects affected / exposed
    323 / 745 (43.36%)
    410 / 854 (48.01%)
         number of deaths (all causes)
    35
    51
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angiosarcoma metastatic
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Adenocarcinoma pancreas
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Basal cell carcinoma
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign neoplasm of thyroid gland
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign anorectal neoplasm
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 745 (0.13%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bladder cancer recurrent
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer stage III
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma recurrent
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma stage I
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain cancer metastatic
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Brain neoplasm malignant
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer male
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chromophobe renal cell carcinoma
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cancer fatigue
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangiocarcinoma
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon adenoma
         subjects affected / exposed
    2 / 745 (0.27%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer stage I
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    2 / 745 (0.27%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enchondromatosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal neoplasm
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer stage III
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal cancer
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Glioblastoma
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lentigo maligna stage I
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal squamous cell carcinoma
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    3 / 745 (0.40%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma stage I
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Lung neoplasm
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung squamous cell carcinoma metastatic
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malignant melanoma
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant neoplasm of unknown primary site
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant palate neoplasm
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphangiosis carcinomatosa
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningioma benign
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lung
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic gastric cancer
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic squamous cell carcinoma
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal neoplasm benign
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine tumour of the lung
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oropharyngeal squamous cell carcinoma
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Non-small cell lung cancer stage IV
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Non-small cell lung cancer metastatic
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancoast's tumour
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ovarian adenoma
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 745 (0.00%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 4
    Pituitary tumour
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 745 (0.00%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Plasma cell myeloma
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural mesothelioma malignant
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural neoplasm
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    6 / 745 (0.81%)
    7 / 854 (0.82%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Prostate cancer metastatic
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer stage I
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer stage II
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic adenoma
         subjects affected / exposed
    1 / 745 (0.13%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal cancer
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Richter's syndrome
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal neoplasm
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin angiosarcoma
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestine carcinoma
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Small intestine carcinoma stage IV
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell cancer of the renal pelvis and ureter
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aneurysm
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    4 / 745 (0.54%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial stenosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral artery aneurysm
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    4 / 745 (0.54%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haematoma
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    4 / 745 (0.54%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery stenosis
         subjects affected / exposed
    1 / 745 (0.13%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    3 / 745 (0.40%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic limb pain
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    12 / 745 (1.61%)
    12 / 854 (1.41%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    2 / 745 (0.27%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    4 / 745 (0.54%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    3 / 745 (0.40%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    1 / 745 (0.13%)
    5 / 854 (0.59%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral vein stenosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian vein thrombosis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pain
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Coronary revascularisation
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implantable defibrillator insertion
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Knee arthroplasty
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileectomy
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin neoplasm excision
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve repair
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    4 / 745 (0.54%)
    7 / 854 (0.82%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Disease progression
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Fibrosis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated hernia
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammation
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Necrosis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    3 / 745 (0.40%)
    10 / 854 (1.17%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 745 (0.13%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stent-graft endoleak
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Unevaluable event
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular stent occlusion
         subjects affected / exposed
    2 / 745 (0.27%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular stent stenosis
         subjects affected / exposed
    3 / 745 (0.40%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular stent thrombosis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anti-neutrophil cytoplasmic antibody positive vasculitis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign prostatic hyperplasia
         subjects affected / exposed
    4 / 745 (0.54%)
    5 / 854 (0.59%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Genital prolapse
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gynaecomastia
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatomegaly
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    3 / 745 (0.40%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Asthma
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis chronic
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    7 / 745 (0.94%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diaphragmatic paralysis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity pneumonitis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal obstruction
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal polyps
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal turbinate hypertrophy
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pickwickian syndrome
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary granuloma
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    3 / 745 (0.40%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    2 / 745 (0.27%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol abuse
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcoholism
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 745 (0.13%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eating disorder
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hallucination, auditory
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Insomnia
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric decompensation
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device occlusion
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device physical property issue
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device material issue
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device power source issue
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary polyp
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    2 / 745 (0.27%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    4 / 745 (0.54%)
    9 / 854 (1.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis obstructive
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    4 / 745 (0.54%)
    5 / 854 (0.59%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure orthostatic
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac function test abnormal
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Echocardiogram abnormal
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio abnormal
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oxygen saturation abnormal
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transvalvular pressure gradient increased
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SARS-CoV-2 antibody test positive
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Abdominal injury
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    2 / 745 (0.27%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    2 / 745 (0.27%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest injury
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Comminuted fracture
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electric injury
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 745 (0.00%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery restenosis
         subjects affected / exposed
    3 / 745 (0.40%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    3 / 745 (0.40%)
    6 / 854 (0.70%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    3 / 745 (0.40%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria traumatic
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    2 / 745 (0.27%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyphaema
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation postoperative
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb traumatic amputation
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device monitoring error
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle rupture
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle contusion
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematoma
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax traumatic
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematuria
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 745 (0.13%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural swelling
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postpericardiotomy syndrome
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pneumothorax
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Restenosis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scapula fracture
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scratch
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin injury
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin wound
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    2 / 745 (0.27%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 745 (0.13%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Splinter
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 745 (0.00%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic arthrosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic haematoma
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access site haemorrhage
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular graft stenosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular graft occlusion
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular anastomosis aneurysm
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular graft thrombosis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound complication
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound haemorrhage
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyloric stenosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Von Hippel-Lindau disease
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    4 / 745 (0.54%)
    7 / 854 (0.82%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    18 / 745 (2.42%)
    15 / 854 (1.76%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    26 / 745 (3.49%)
    24 / 854 (2.81%)
         occurrences causally related to treatment / all
    0 / 31
    0 / 28
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    15 / 745 (2.01%)
    13 / 854 (1.52%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve calcification
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    15 / 745 (2.01%)
    22 / 854 (2.58%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 28
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    2 / 745 (0.27%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    17 / 745 (2.28%)
    27 / 854 (3.16%)
         occurrences causally related to treatment / all
    0 / 25
    0 / 38
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Cardiac failure acute
         subjects affected / exposed
    2 / 745 (0.27%)
    6 / 854 (0.70%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    2 / 745 (0.27%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    6 / 745 (0.81%)
    5 / 854 (0.59%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiogenic shock
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiorenal syndrome
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    6 / 745 (0.81%)
    10 / 854 (1.17%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic coronary syndrome
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congestive cardiomyopathy
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    2 / 745 (0.27%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    5 / 745 (0.67%)
    11 / 854 (1.29%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery thrombosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary ostial stenosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dressler's syndrome
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extrasystoles
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular hypertrophy
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    3 / 745 (0.40%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Low cardiac output syndrome
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 745 (0.13%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve stenosis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    7 / 745 (0.94%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    6 / 745 (0.81%)
    9 / 854 (1.05%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Pericardial effusion
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinoatrial block
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    2 / 745 (0.27%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    8 / 745 (1.07%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    3 / 745 (0.40%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid artery stenosis
         subjects affected / exposed
    3 / 745 (0.40%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral artery embolism
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid arteriosclerosis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Amputation stump pain
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral atrophy
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    2 / 745 (0.27%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    4 / 745 (0.54%)
    6 / 854 (0.70%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebral thrombosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dementia
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervicobrachial syndrome
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    2 / 745 (0.27%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia with Lewy bodies
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    3 / 745 (0.40%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Essential tremor
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    2 / 745 (0.27%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dysaesthesia
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiplegia
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraventricular haemorrhage
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    8 / 745 (1.07%)
    14 / 854 (1.64%)
         occurrences causally related to treatment / all
    0 / 9
    1 / 16
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Memory impairment
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nerve compression
         subjects affected / exposed
    2 / 745 (0.27%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normal pressure hydrocephalus
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral nerve lesion
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Piriformis syndrome
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post-traumatic headache
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 745 (0.13%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatic nerve neuropathy
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    2 / 745 (0.27%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    10 / 745 (1.34%)
    10 / 854 (1.17%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient global amnesia
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    9 / 745 (1.21%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VIth nerve paralysis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Coagulopathy
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    2 / 745 (0.27%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic disorder
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrotic lymphadenopathy
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Meniere's disease
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden hearing loss
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    0 / 745 (0.00%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Blepharitis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blindness
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Corneal oedema
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diplopia
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Keratopathy
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lens dislocation
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual impairment
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 745 (0.13%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 745 (0.13%)
    5 / 854 (0.59%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis microscopic
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dental caries
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Enlarged uvula
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric cyst
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 745 (0.27%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal ulcer
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal vascular malformation haemorrhagic
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar hernia
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive pancreatitis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mesenteric vein thrombosis
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedematous pancreatitis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic cyst
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    2 / 745 (0.27%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    2 / 745 (0.27%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal haematoma
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal polyp
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Volvulus of small bowel
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prurigo
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pruritus
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertrichosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic skin ulcer
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin necrosis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus bladder
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urethral
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    6 / 745 (0.81%)
    8 / 854 (0.94%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis noninfective
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    2 / 745 (0.27%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Micturition disorder
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    4 / 745 (0.54%)
    5 / 854 (0.59%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric stenosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paroxysmal nocturnal haemoglobinuria
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral obstruction
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    2 / 745 (0.27%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary bladder polyp
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinoma
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal haemorrhage
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia of malignancy
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chondrocalcinosis pyrophosphate
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Compartment syndrome
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Exostosis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma muscle
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inclusion body myositis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc compression
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    1 / 745 (0.13%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    3 / 745 (0.40%)
    6 / 854 (0.70%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle spasms
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteitis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    8 / 745 (1.07%)
    15 / 854 (1.76%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patellofemoral pain syndrome
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psoriatic arthropathy
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polymyalgia rheumatica
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    2 / 745 (0.27%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    7 / 745 (0.94%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon disorder
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon pain
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 745 (0.13%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess jaw
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal abscess
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    6 / 745 (0.81%)
    5 / 854 (0.59%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bronchitis
         subjects affected / exposed
    0 / 745 (0.00%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 745 (0.27%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Campylobacter gastroenteritis
         subjects affected / exposed
    2 / 745 (0.27%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 745 (0.00%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis infective
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    2 / 745 (0.27%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermo-hypodermitis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis intestinal haemorrhagic
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    7 / 745 (0.94%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 745 (0.13%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis bacterial
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Groin abscess
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis A
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster cutaneous disseminated
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 745 (0.13%)
    5 / 854 (0.59%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Infectious pleural effusion
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    3 / 745 (0.40%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella infection
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphangitis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis streptococcal
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mediastinal abscess
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral infection
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    15 / 745 (2.01%)
    19 / 854 (2.22%)
         occurrences causally related to treatment / all
    0 / 17
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia aspiration
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    3 / 745 (0.40%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    2 / 745 (0.27%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis Escherichia coli
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyelonephritis
         subjects affected / exposed
    0 / 745 (0.00%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 745 (0.40%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic embolus
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    4 / 745 (0.54%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatococcal infection
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    0 / 745 (0.00%)
    3 / 854 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    4 / 745 (0.54%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Urosepsis
         subjects affected / exposed
    3 / 745 (0.40%)
    4 / 854 (0.47%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Vascular device infection
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    3 / 745 (0.40%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abnormal loss of weight
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    2 / 745 (0.27%)
    5 / 854 (0.59%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    3 / 745 (0.40%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Folate deficiency
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 745 (0.13%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    2 / 745 (0.27%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    2 / 745 (0.27%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    2 / 745 (0.27%)
    2 / 854 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    2 / 745 (0.27%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    2 / 745 (0.27%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overweight
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Steroid diabetes
         subjects affected / exposed
    1 / 745 (0.13%)
    0 / 854 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 745 (0.00%)
    1 / 854 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo in Parent Study Evolocumab in Parent Study
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    451 / 745 (60.54%)
    528 / 854 (61.83%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    132 / 745 (17.72%)
    150 / 854 (17.56%)
         occurrences all number
    159
    179
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    37 / 745 (4.97%)
    49 / 854 (5.74%)
         occurrences all number
    39
    55
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    33 / 745 (4.43%)
    43 / 854 (5.04%)
         occurrences all number
    38
    50
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    40 / 745 (5.37%)
    29 / 854 (3.40%)
         occurrences all number
    45
    34
    Eye disorders
    Cataract
         subjects affected / exposed
    42 / 745 (5.64%)
    32 / 854 (3.75%)
         occurrences all number
    49
    43
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    39 / 745 (5.23%)
    40 / 854 (4.68%)
         occurrences all number
    42
    44
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    61 / 745 (8.19%)
    75 / 854 (8.78%)
         occurrences all number
    77
    87
    Back pain
         subjects affected / exposed
    50 / 745 (6.71%)
    70 / 854 (8.20%)
         occurrences all number
    55
    80
    Myalgia
         subjects affected / exposed
    55 / 745 (7.38%)
    47 / 854 (5.50%)
         occurrences all number
    60
    55
    Pain in extremity
         subjects affected / exposed
    24 / 745 (3.22%)
    50 / 854 (5.85%)
         occurrences all number
    27
    55
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    42 / 745 (5.64%)
    41 / 854 (4.80%)
         occurrences all number
    47
    57
    Nasopharyngitis
         subjects affected / exposed
    75 / 745 (10.07%)
    111 / 854 (13.00%)
         occurrences all number
    97
    155
    Influenza
         subjects affected / exposed
    37 / 745 (4.97%)
    53 / 854 (6.21%)
         occurrences all number
    37
    56
    Bronchitis
         subjects affected / exposed
    32 / 745 (4.30%)
    43 / 854 (5.04%)
         occurrences all number
    49
    55
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    60 / 745 (8.05%)
    57 / 854 (6.67%)
         occurrences all number
    61
    61

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Dec 2018
    The protocol was amended for the following reasons: • Financial disclosure statement text was removed as this was not applicable to this study (only European sites were participating). • An independent external CEC was established and reviewed deaths and cardiovascular events of interest; cardiovascular events of interest to be reviewed were defined. • The term “targeted” concomitant therapy was removed throughout; all concomitant therapy was assessed. • Statistical considerations were clarified to include that the primary analysis of all endpoints in the OLE study will only use OLE study data and how CEC events were analyzed. • Exposure time intervals were modified. • The text was clarified to indicate that the lipid profiles are conducted at scheduled visits and not on a yearly basis and week 260 was removed as part of end of study definition. • The information collected for concomitant therapy for disease under study, antibiotics, and then all other therapies was clarified. • Male contraception language removed as not applicable. • Clarification of how data were collected and defined when a subject transitions from parent to OLE study, including medical history and what data were transferred to OLE study was added. • Redundant text for subject withdrawal and concomitant therapy was removed. • The resupply period was clarified. • Lot number was changed to box number for accuracy. • Lost to follow-up section was added for clarity.
    19 Feb 2020
    The protocol was amended for the following reasons: • The safety section was updated to reflect that all serious drug-related events must be recorded and reported to the sponsor or designee within 24 hours. • “Coronary revascularization” was included throughout the protocol to identify the specific vascular territory of interest, which is the coronary circulation. • The identified Events of Interest (EOIs) were removed from the protocol and are no longer prespecified. • Week 260 was added back into the schedule of assessments to realign with the 20130295 sister study. • Coronary revascularization procedure and death information was added throughout to support the independent safety review of cardiovascular EOIs and deaths by the CEC. • Dosing details were clarified including details regarding the switch frequency between AI/pen and personal injector were added, and the last resupply of evolocumab will occur 12 weeks after the week 240 visit. • Updated the exploratory objectives to be consistent with exploratory endpoints. • Remove language in the definition of Primary Completion to align with current protocol template.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    This study was terminated to coincide with the completion of study 20130295 (NCT02867813). The study was not terminated due to any safety findings.
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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