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    Clinical Trial Results:
    A randomized, multi-center Phase IIIb, open label, study of letrozole vs anastrozole in the adjuvant treatment of postmenopausal women with hormone receptor and node positive breast cancer Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.

    Summary
    EudraCT number
    		 2005-004263-35
    Trial protocol
    		 IE   FI   ES   SE   GB   AT   DK   BE   DE   IT  
    Global end of trial date
    08 Sep 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Jul 2018
    First version publication date
    06 Jul 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CFEM345D2411
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00248170
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
    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
    08 Sep 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Sep 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to compare the rate of disease-free survival (DFS) when 959 DFS events had occurred in postmenopausal women with hormone receptor and lymph node positive breast cancer randomized between letrozole and anastrozole.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Dec 2005
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy
    Long term follow-up duration
    		 3 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 301
    Country: Number of subjects enrolled
    Austria: 198
    Country: Number of subjects enrolled
    Belgium: 139
    Country: Number of subjects enrolled
    Canada: 124
    Country: Number of subjects enrolled
    China: 38
    Country: Number of subjects enrolled
    Denmark: 270
    Country: Number of subjects enrolled
    Finland: 21
    Country: Number of subjects enrolled
    France: 206
    Country: Number of subjects enrolled
    Germany: 358
    Country: Number of subjects enrolled
    Ireland: 165
    Country: Number of subjects enrolled
    Israel: 103
    Country: Number of subjects enrolled
    Italy: 305
    Country: Number of subjects enrolled
    Japan: 297
    Country: Number of subjects enrolled
    Korea, Republic of: 30
    Country: Number of subjects enrolled
    Netherlands: 85
    Country: Number of subjects enrolled
    New Zealand: 65
    Country: Number of subjects enrolled
    Norway: 13
    Country: Number of subjects enrolled
    Spain: 104
    Country: Number of subjects enrolled
    Sweden: 59
    Country: Number of subjects enrolled
    Switzerland: 20
    Country: Number of subjects enrolled
    United Kingdom: 282
    Country: Number of subjects enrolled
    United States: 953
    Worldwide total number of subjects
    4136
    EEA total number of subjects
    2205
    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)
    2490
    From 65 to 84 years
    1646
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants, who had recently undergone surgery, were randomly assigned in 1:1 ratio to letrozole or anastrozole. Participants received daily treatment until disease recurrence/relapse or for a maximum of 5 years. Participants underwent post-treatment long term follow-up for disease-free survival and overall survival.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Letrozole
    Arm description
    		 2.5 mg by mouth (p.o.) once daily
    Arm type
    		 Experimental

    Investigational medicinal product name
    Letrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    2.5 mg orally once a day

    Arm title
    		 Anastrozole
    Arm description
    		 1 mg p.o. once daily
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Anastrozole
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg orally once a day

    Number of subjects in period 1
    		Letrozole Anastrozole
    Started
    2061
    2075
    Intent-to-treat (ITT)
    2061
    2075
    Safety set
    2049
    2062
    Completed
    1317
    1286
    Not completed
    744
    789
         Adverse event, serious fatal
    28
    47
         Consent withdrawn by subject
    71
    79
         Disease progression
    196
    216
         Abnormal test procedure(s) result
    49
    61
         Adverse event, non-fatal
    311
    296
         Administrative problems
    22
    25
         Abnormal laboratory values
    4
    -
         Lost to follow-up
    28
    35
         Protocol deviation
    35
    30

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Letrozole
    Reporting group description
    		 2.5 mg by mouth (p.o.) once daily

    Reporting group title
    Anastrozole
    Reporting group description
    		 1 mg p.o. once daily

    Reporting group values
    		 Letrozole Anastrozole Total
    Number of subjects
    		 2061 2075 4136
    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)
    		 1236 1254 2490
        From 65-84 years
    		 806 802 1608
        85 years and over
    		 19 19 38
    Age Continuous |
    Units: Years
        arithmetic mean (standard deviation)
    		 63.2 ( 8.48 ) 63.1 ( 8.45 ) -
    Gender categorical
    Units: Subjects
        Female
    		 2061 2075 4136
        Male
    		 0 0 0
    Gender, Customized
    Units: Subjects
        Female
    		 2061 2075 4136

    End points

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    End points reporting groups
    Reporting group title
    Letrozole
    Reporting group description
    		 2.5 mg by mouth (p.o.) once daily

    Reporting group title
    Anastrozole
    Reporting group description
    		 1 mg p.o. once daily

    Primary: Disease free survival

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    End point title
    		 Disease free survival
    End point description
    Disease-free survival was defined as the time from the date of randomization to the date of the first documentation of re-occurrence of invasive breast cancer in local, regional or distant sites, new invasive breast cancer in the contra-lateral breast, or death from any cause.
    End point type
    Primary
    End point timeframe
    84 months
    End point values
    		 Letrozole Anastrozole
    Number of subjects analysed
    2061
    2075
    Units: Months
        median (confidence interval)
    999 (84.14 to 999)
    999 (-999 to 999)
    Statistical analysis title
    		 Disease free survival
    Comparison groups
    Anastrozole v Letrozole
    Number of subjects included in analysis
    4136
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.315
    Method
    		 Logrank
    Confidence interval

    Secondary: Overall survival

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    End point title
    		 Overall survival
    End point description
    Overall survival was defined as the time from the date of randomization to the date of death from any cause.
    End point type
    Secondary
    End point timeframe
    84 months
    End point values
    		 Letrozole Anastrozole
    Number of subjects analysed
    2061
    2075
    Units: Months
        median (confidence interval)
    999 (-999 to 999)
    999 (-999 to 999)
    No statistical analyses for this end point

    Secondary: Time to development of distant metastases

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    End point title
    		 Time to development of distant metastases
    End point description
    Time to development of distant metastases was defined as the time from date of randomization to the date of the first development of any recurrent or metastatic disease in sites other than the local mastectomy scar, the ipsilateral breast in case of breast conservation or the contra lateral breast.
    End point type
    Secondary
    End point timeframe
    84 months
    End point values
    		 Letrozole Anastrozole
    Number of subjects analysed
    2061
    2075
    Units: Months
        median (confidence interval)
    999 (84.14 to 999)
    999 (-999 to 999)
    No statistical analyses for this end point

    Secondary: Time to development of contra lateral breast cancer

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    End point title
    		 Time to development of contra lateral breast cancer
    End point description
    Time to development of contra lateral breast cancer was defined as the time from the date of randomization to the date of the first development of any disease in the contra lateral breast.
    End point type
    Secondary
    End point timeframe
    84 months
    End point values
    		 Letrozole Anastrozole
    Number of subjects analysed
    2061
    2075
    Units: Months
        median (confidence interval)
    999 (-999 to 999)
    999 (-999 to 999)
    No statistical analyses for this end point

    Secondary: Distant disease-free survival

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    End point title
    		 Distant disease-free survival
    End point description
    Distant disease-free survival was defined as the time from date of randomization to the date of the first development of any relapse at a distant site or death from any cause.
    End point type
    Secondary
    End point timeframe
    84 months
    End point values
    		 Letrozole Anastrozole
    Number of subjects analysed
    2061
    2075
    Units: Months
        median (confidence interval)
    999 (84.14 to 999)
    999 (-999 to 999)
    No statistical analyses for this end point

    Secondary: Change from baseline in serum lipid profiles

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    End point title
    		 Change from baseline in serum lipid profiles
    End point description
    Total cholesterol was analyzed to assess the impact on serum lipids profiles. The adjusted means was calculated.
    End point type
    Secondary
    End point timeframe
    baseline, 6, 12, 24, 36, 48 and 60 months
    End point values
    		 Letrozole Anastrozole
    Number of subjects analysed
    2049
    2062
    Units: mg/dL
    arithmetic mean (confidence interval)
        6 months
    5.643 (5.584 to 5.701)
    5.553 (5.495 to 5.611)
        12 months
    5.569 (5.51 to 5.629)
    5.511 (5.452 to 5.57)
        24 months
    5.508 (5.445 to 5.572)
    5.436 (5.373 to 5.499)
        36 months
    5.429 (5.359 to 5.5)
    5.427 (5.357 to 5.497)
        48 months
    5.395 (5.323 to 5.468)
    5.366 (5.293 to 5.438)
        60 months
    5.375 (5.3 to 5.451)
    5.368 (5.292 to 5.443)
    No statistical analyses for this end point

    Secondary: Percentage of participants who experienced clinical fracture events

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    End point title
    		 Percentage of participants who experienced clinical fracture events
    End point description
    The incidence of clinical fractures was analyzed.
    End point type
    Secondary
    End point timeframe
    84 months
    End point values
    		 Letrozole Anastrozole
    Number of subjects analysed
    2049
    2062
    Units: Percentage of participants
        number (not applicable)
    9.3
    8.1
    No statistical analyses for this end point

    Secondary: Percentage of participants who experienced cardiovascular events

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    End point title
    		 Percentage of participants who experienced cardiovascular events
    End point description
    The incidence of ischemic heart disease, cardiac failures, cerebrovascular accidents and thromboembolic events was analyzed.
    End point type
    Secondary
    End point timeframe
    84 months
    End point values
    		 Letrozole Anastrozole
    Number of subjects analysed
    2049
    2062
    Units: Percentage of participants
    number (not applicable)
        Ischemic heart disease
    2.4
    1.5
        Cardiac failures
    1.5
    0.7
        Cerebrovascular accidents
    1.6
    1.5
        Thromboembolic events
    1.2
    1.2
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Anastrozole
    Reporting group description
    		 Anastrozole

    Reporting group title
    Letrozole
    Reporting group description
    		 Letrozole

    Serious adverse events
    		 Anastrozole Letrozole
    Total subjects affected by serious adverse events
         subjects affected / exposed
    520 / 2062 (25.22%)
    485 / 2049 (23.67%)
         number of deaths (all causes)
    46
    42
         number of deaths resulting from adverse events
    2
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma of the cervix
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angiomyolipoma
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign laryngeal neoplasm
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign lymph node neoplasm
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign neoplasm
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign neoplasm of thyroid gland
         subjects affected / exposed
    3 / 2062 (0.15%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign salivary gland neoplasm
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone cancer
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon neoplasm
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diffuse large B-cell lymphoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibroma
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibromatosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder cancer
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal carcinoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal tract adenoma
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemangioma
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cancer
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lip and/or oral cavity cancer
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lip neoplasm benign
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lymphangiosis carcinomatosa
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma in situ
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant peritoneal neoplasm
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant pleural effusion
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to abdominal cavity
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to peritoneum
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastatic pain
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurilemmoma benign
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cancer stage III
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Ovarian fibroma
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian neoplasm
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pituitary tumour benign
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleomorphic adenoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal adenoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectosigmoid cancer
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Retro-orbital neoplasm
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salivary gland neoplasm
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Schwannoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seborrhoeic keratosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Signet-ring cell carcinoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    4 / 2062 (0.19%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superficial spreading melanoma stage unspecified
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid adenoma
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid neoplasm
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Waldenstrom's macroglobulinaemia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Aortic aneurysm rupture
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Aortic dissection
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Aortic stenosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic thrombosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial disorder
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arterial occlusive disease
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Capillary fragility
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    4 / 2062 (0.19%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    8 / 2062 (0.39%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    2 / 8
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral artery occlusion
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    2 / 2062 (0.10%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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 / 2062 (0.19%)
    7 / 2049 (0.34%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 2062 (0.00%)
    4 / 2049 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 2062 (0.05%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hypovolaemic shock
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intra-abdominal haematoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphoedema
         subjects affected / exposed
    3 / 2062 (0.15%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral venous disease
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Temporal arteritis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thromboangiitis obliterans
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vena cava thrombosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Breast lump removal
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast operation
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast prosthesis implantation
         subjects affected / exposed
    10 / 2062 (0.48%)
    5 / 2049 (0.24%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast prosthesis removal
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast reconstruction
         subjects affected / exposed
    16 / 2062 (0.78%)
    24 / 2049 (1.17%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 27
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central venous catheter removal
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Knee arthroplasty
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mammoplasty
         subjects affected / exposed
    3 / 2062 (0.15%)
    6 / 2049 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mastectomy
         subjects affected / exposed
    6 / 2062 (0.29%)
    5 / 2049 (0.24%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mechanical ventilation
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device removal
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus removal
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Modified radical mastectomy
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Removal of internal fixation
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scar excision
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal laminectomy
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound treatment
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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
    6 / 2062 (0.29%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac death
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Chest discomfort
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    2 / 2062 (0.10%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Device damage
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    2 / 2062 (0.10%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease recurrence
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drowning
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Fat necrosis
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    3 / 2062 (0.15%)
    4 / 2049 (0.20%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implant site extravasation
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site phlebitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (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
    3 / 2062 (0.15%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 2062 (0.10%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patient-device incompatibility
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    8 / 2062 (0.39%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Thrombosis in device
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sarcoidosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Adnexa uteri mass
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anisomastia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast calcifications
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast haematoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast fibrosis
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast inflammation
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast mass
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast oedema
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colpocele
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystocele
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Female genital tract fistula
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Genital prolapse
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metrorrhagia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nipple disorder
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nipple exudate bloody
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    3 / 2062 (0.15%)
    5 / 2049 (0.24%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic prolapse
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perineal pain
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectocele
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine fistula
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Uterine polyp
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal inflammation
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal prolapse
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    3 / 2062 (0.15%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Choking
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    9 / 2062 (0.44%)
    6 / 2049 (0.29%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 6
         deaths causally related to treatment / all
    0 / 4
    0 / 0
    Dyspnoea
         subjects affected / exposed
    7 / 2062 (0.34%)
    10 / 2049 (0.49%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercapnia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Pleural effusion
         subjects affected / exposed
    3 / 2062 (0.15%)
    5 / 2049 (0.24%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    3 / 2062 (0.15%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Productive cough
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    12 / 2062 (0.58%)
    6 / 2049 (0.29%)
         occurrences causally related to treatment / all
    4 / 12
    1 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    3 / 2062 (0.15%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Sinus congestion
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Abnormal behaviour
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Agitation
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Confusional state
         subjects affected / exposed
    8 / 2062 (0.39%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depressed mood
         subjects affected / exposed
    3 / 2062 (0.15%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    11 / 2062 (0.53%)
    9 / 2049 (0.44%)
         occurrences causally related to treatment / all
    1 / 14
    1 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug dependence
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intentional self-injury
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    2 / 2062 (0.10%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mood disorder due to a general medical condition
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mood swings
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somatisation disorder
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Amylase increased
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration pleural cavity
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biopsy breast
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biopsy lymph gland
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone density decreased
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carbohydrate antigen 15-3 increased
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium test positive
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibrin D dimer increased
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipase increased
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mammogram abnormal
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mediastinal biopsy
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (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 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight increased
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Acetabulum fracture
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (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
    10 / 2062 (0.48%)
    14 / 2049 (0.68%)
         occurrences causally related to treatment / all
    1 / 10
    5 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthropod bite
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (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
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Compression fracture
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dislocation of vertebra
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Excoriation
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Face injury
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    13 / 2062 (0.63%)
    17 / 2049 (0.83%)
         occurrences causally related to treatment / all
    0 / 13
    1 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Femoral neck fracture
         subjects affected / exposed
    3 / 2062 (0.15%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 2062 (0.10%)
    8 / 2049 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    2 / 2062 (0.10%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    4 / 2062 (0.19%)
    5 / 2049 (0.24%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    6 / 2062 (0.29%)
    9 / 2049 (0.44%)
         occurrences causally related to treatment / all
    1 / 6
    1 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    2 / 2062 (0.10%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    4 / 2062 (0.19%)
    4 / 2049 (0.20%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    4 / 2062 (0.19%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    3 / 2062 (0.15%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle rupture
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle strain
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    3 / 2062 (0.15%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 2062 (0.00%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax traumatic
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural hypothyroidism
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative hernia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound complication
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary contusion
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation pericarditis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation pneumonitis
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation skin injury
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    7 / 2062 (0.34%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 7
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 2062 (0.05%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (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
    4 / 2062 (0.19%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue injury
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    2 / 2062 (0.10%)
    6 / 2049 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    3 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic rupture
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sternal fracture
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    2 / 2062 (0.10%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 2062 (0.00%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheal injury
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    5 / 2062 (0.24%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    3 / 2062 (0.15%)
    6 / 2049 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syndactyly
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vitello-intestinal duct remnant
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (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
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    4 / 2062 (0.19%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Adams-Stokes syndrome
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    8 / 2062 (0.39%)
    8 / 2049 (0.39%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    2 / 2062 (0.10%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    15 / 2062 (0.73%)
    19 / 2049 (0.93%)
         occurrences causally related to treatment / all
    1 / 15
    1 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bundle branch block
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    4 / 2062 (0.19%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Cardiac disorder
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    3 / 2062 (0.15%)
    9 / 2049 (0.44%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 11
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    Cardiac failure acute
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 2062 (0.00%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    4 / 2062 (0.19%)
    9 / 2049 (0.44%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac fibrillation
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (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
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conduction disorder
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (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
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cor pulmonale
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery disease
         subjects affected / exposed
    2 / 2062 (0.10%)
    7 / 2049 (0.34%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrocardiac syndrome
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve disease
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    4 / 2062 (0.19%)
    5 / 2049 (0.24%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    2 / 2062 (0.10%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Restrictive cardiomyopathy
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sick sinus syndrome
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachyarrhythmia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 2062 (0.00%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tricuspid valve incompetence
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Balance disorder
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    6 / 2062 (0.29%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    4 / 7
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral amyloid angiopathy
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    6 / 2062 (0.29%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    5 / 2062 (0.24%)
    8 / 2049 (0.39%)
         occurrences causally related to treatment / all
    0 / 5
    3 / 9
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cervicobrachial syndrome
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    3 / 2062 (0.15%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia Alzheimer's type
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dizziness
         subjects affected / exposed
    6 / 2062 (0.29%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial paresis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Headache
         subjects affected / exposed
    4 / 2062 (0.19%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Horner's syndrome
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypogeusia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Monoplegia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple sclerosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple sclerosis relapse
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Optic neuritis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parkinsonism
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Petit mal epilepsy
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sensory loss
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Speech disorder
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal claudication
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal epidural haemorrhage
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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
    4 / 2062 (0.19%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Syncope
         subjects affected / exposed
    4 / 2062 (0.19%)
    13 / 2049 (0.63%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tardive dyskinesia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient global amnesia
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    5 / 2062 (0.24%)
    8 / 2049 (0.39%)
         occurrences causally related to treatment / all
    1 / 5
    2 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VIIth nerve paralysis
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (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
    Anaemia
         subjects affected / exposed
    3 / 2062 (0.15%)
    4 / 2049 (0.20%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic anaemia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Hearing impaired
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inner ear disorder
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tinnitus
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tympanic membrane perforation
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    1 / 2062 (0.05%)
    8 / 2049 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    2 / 2062 (0.10%)
    9 / 2049 (0.44%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dacryostenosis acquired
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diplopia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lens dislocation
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Macular hole
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Open angle glaucoma
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal vein thrombosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vision blurred
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal adhesions
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    5 / 2062 (0.24%)
    9 / 2049 (0.44%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    3 / 2062 (0.15%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    7 / 2062 (0.34%)
    6 / 2049 (0.29%)
         occurrences causally related to treatment / all
    1 / 7
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall haematoma
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal sphincter atony
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis microscopic
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 2062 (0.15%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    5 / 2062 (0.24%)
    8 / 2049 (0.39%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (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
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterovesical fistula
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faecal incontinence
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faeces discoloured
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral hernia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer perforation
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    5 / 2062 (0.24%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    3 / 2062 (0.15%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    3 / 2062 (0.15%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    3 / 2062 (0.15%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammatory bowel disease
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    2 / 2062 (0.10%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal dilatation
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    2 / 2062 (0.10%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    2 / 2062 (0.10%)
    7 / 2049 (0.34%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mouth cyst
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    6 / 2062 (0.29%)
    11 / 2049 (0.54%)
         occurrences causally related to treatment / all
    1 / 6
    2 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    2 / 2062 (0.10%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    5 / 2062 (0.24%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    3 / 2062 (0.15%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spigelian hernia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth loss
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Volvulus
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    6 / 2062 (0.29%)
    11 / 2049 (0.54%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    5 / 2062 (0.24%)
    7 / 2049 (0.34%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    11 / 2062 (0.53%)
    8 / 2049 (0.39%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder perforation
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder polyp
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic steatosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermal cyst
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erythema multiforme
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erythrodermic psoriasis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertrophic scar
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Keloid scar
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (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
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin lesion
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin necrosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria chronic
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus bladder
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus ureteric
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    3 / 2062 (0.15%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertonic bladder
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    2 / 2062 (0.10%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyuria
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    7 / 2062 (0.34%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Renal failure acute
         subjects affected / exposed
    2 / 2062 (0.10%)
    6 / 2049 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure chronic
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress urinary incontinence
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral caruncle
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral obstruction
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    4 / 2062 (0.19%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Goitre
         subjects affected / exposed
    2 / 2062 (0.10%)
    4 / 2049 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperparathyroidism
         subjects affected / exposed
    3 / 2062 (0.15%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic nodular goitre
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    6 / 2062 (0.29%)
    9 / 2049 (0.44%)
         occurrences causally related to treatment / all
    5 / 6
    3 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    9 / 2062 (0.44%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    2 / 10
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    10 / 2062 (0.48%)
    6 / 2049 (0.29%)
         occurrences causally related to treatment / all
    1 / 10
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Compartment syndrome
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    6 / 2062 (0.29%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint instability
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint stiffness
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kyphosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loose body in joint
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle atrophy
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle spasms
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    4 / 2062 (0.19%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    3 / 2062 (0.15%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myopathy
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    15 / 2062 (0.73%)
    21 / 2049 (1.02%)
         occurrences causally related to treatment / all
    1 / 15
    0 / 26
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteopenia
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoporosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyarthritis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudarthrosis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    2 / 2062 (0.10%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    1 / 2062 (0.05%)
    4 / 2049 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tenosynovitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Trigger finger
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess soft tissue
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    5 / 2062 (0.24%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast abscess
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cellulitis
         subjects affected / exposed
    4 / 2062 (0.19%)
    6 / 2049 (0.29%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    4 / 2062 (0.19%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    9 / 2062 (0.44%)
    8 / 2049 (0.39%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    3 / 2062 (0.15%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    3 / 2062 (0.15%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    7 / 2062 (0.34%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Erysipelas
         subjects affected / exposed
    8 / 2062 (0.39%)
    5 / 2049 (0.24%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder empyema
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 2062 (0.10%)
    7 / 2049 (0.34%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis Escherichia coli
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Helicobacter infection
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    2 / 2062 (0.10%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site abscess
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    3 / 2062 (0.15%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 2062 (0.05%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    4 / 2062 (0.19%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lymphangitis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mastitis
         subjects affected / exposed
    5 / 2062 (0.24%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nosocomial infection
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    2 / 2062 (0.10%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal abscess
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    29 / 2062 (1.41%)
    16 / 2049 (0.78%)
         occurrences causally related to treatment / all
    0 / 30
    0 / 19
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Pneumonia klebsiella
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia legionella
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural cellulitis
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural pneumonia
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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 / 2062 (0.10%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomonas bronchitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    2 / 2062 (0.10%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyometra
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         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
    3 / 2062 (0.15%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    8 / 2062 (0.39%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Skin infection
         subjects affected / exposed
    3 / 2062 (0.15%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    8 / 2062 (0.39%)
    7 / 2049 (0.34%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urosepsis
         subjects affected / exposed
    3 / 2062 (0.15%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal infection
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral diarrhoea
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulvitis
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 2062 (0.05%)
    3 / 2049 (0.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 2062 (0.05%)
    7 / 2049 (0.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    2 / 2062 (0.10%)
    4 / 2049 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 2062 (0.00%)
    2 / 2049 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 2062 (0.00%)
    4 / 2049 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypophagia
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    1 / 2062 (0.05%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    0 / 2062 (0.00%)
    1 / 2049 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 2062 (0.05%)
    0 / 2049 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Anastrozole Letrozole
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1762 / 2062 (85.45%)
    1747 / 2049 (85.26%)
    Injury, poisoning and procedural complications
    Radiation skin injury
         subjects affected / exposed
    88 / 2062 (4.27%)
    120 / 2049 (5.86%)
         occurrences all number
    88
    121
    Vascular disorders
    Hot flush
         subjects affected / exposed
    666 / 2062 (32.30%)
    666 / 2049 (32.50%)
         occurrences all number
    714
    702
    Hypertension
         subjects affected / exposed
    145 / 2062 (7.03%)
    152 / 2049 (7.42%)
         occurrences all number
    148
    152
    Lymphoedema
         subjects affected / exposed
    177 / 2062 (8.58%)
    158 / 2049 (7.71%)
         occurrences all number
    182
    165
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    107 / 2062 (5.19%)
    92 / 2049 (4.49%)
         occurrences all number
    116
    99
    Headache
         subjects affected / exposed
    164 / 2062 (7.95%)
    127 / 2049 (6.20%)
         occurrences all number
    184
    134
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    341 / 2062 (16.54%)
    345 / 2049 (16.84%)
         occurrences all number
    362
    368
    Oedema peripheral
         subjects affected / exposed
    104 / 2062 (5.04%)
    100 / 2049 (4.88%)
         occurrences all number
    109
    106
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    148 / 2062 (7.18%)
    127 / 2049 (6.20%)
         occurrences all number
    162
    139
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    120 / 2062 (5.82%)
    106 / 2049 (5.17%)
         occurrences all number
    122
    115
    Dyspnoea
         subjects affected / exposed
    92 / 2062 (4.46%)
    111 / 2049 (5.42%)
         occurrences all number
    94
    121
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    134 / 2062 (6.50%)
    126 / 2049 (6.15%)
         occurrences all number
    137
    131
    Psychiatric disorders
    Depression
         subjects affected / exposed
    129 / 2062 (6.26%)
    141 / 2049 (6.88%)
         occurrences all number
    133
    144
    Insomnia
         subjects affected / exposed
    149 / 2062 (7.23%)
    160 / 2049 (7.81%)
         occurrences all number
    154
    165
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    983 / 2062 (47.67%)
    983 / 2049 (47.97%)
         occurrences all number
    1192
    1181
    Back pain
         subjects affected / exposed
    187 / 2062 (9.07%)
    207 / 2049 (10.10%)
         occurrences all number
    199
    229
    Bone pain
         subjects affected / exposed
    120 / 2062 (5.82%)
    138 / 2049 (6.73%)
         occurrences all number
    127
    143
    Musculoskeletal pain
         subjects affected / exposed
    144 / 2062 (6.98%)
    122 / 2049 (5.95%)
         occurrences all number
    156
    129
    Myalgia
         subjects affected / exposed
    211 / 2062 (10.23%)
    232 / 2049 (11.32%)
         occurrences all number
    223
    254
    Osteopenia
         subjects affected / exposed
    172 / 2062 (8.34%)
    202 / 2049 (9.86%)
         occurrences all number
    172
    203
    Osteoporosis
         subjects affected / exposed
    224 / 2062 (10.86%)
    221 / 2049 (10.79%)
         occurrences all number
    225
    223
    Pain in extremity
         subjects affected / exposed
    174 / 2062 (8.44%)
    167 / 2049 (8.15%)
         occurrences all number
    193
    191
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    151 / 2062 (7.32%)
    155 / 2049 (7.56%)
         occurrences all number
    151
    160

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Jan 2006
    The protocol was updated to reflect the 2005 St Gallen’s Early Breast Cancer consensus guidelines and the 2004 ASCO guidelines for the use of aromatase inhibitors for the adjuvant treatment of breast cancer and the use of bisphosphonates (Goldhirsch et al 2005, Winer et al Also, the steering committee recommended clear guidelines for different parties involved in the conduct of the trial including an independent group to control the analysis since the medication was not blinded.
    19 Sep 2006
    The protocol was amended to incorporate participating investigators’ feedback after enrolling their initial patients to the study. They suggested the protocol be consistent with its approach of using standard institutional practices rather than a mix of pre-specified examinations and standard care since there was extensive experience with both of these agents in terms of safety. Both agents received approval for this indication by multiple health authorities around the world. Also, the steering committee reconsidered the inclusion of patients who had received neo-adjuvant chemotherapy and revised the treatment guidelines for patients with hyperlipidemia. The secondary objectives were updated to include distant disease-free survival with appropriate statistical methodology added to include this in the statistical plan.
    10 May 2007
    This amendment provided additional details concerning the central review of hormone receptors and HER2 status and added the central confirmation as a secondary objective for the study. Central confirmation of ER, PgR, and HER2 were mandatory for centers except where prohibited by regulations. Centers were asked to reconsent patients who had already been enrolled prior to the approval of amendment 3, if needed in order to ship their tumor blocks for central confirmation. Breast cancer researchers in general, strongly encouraged sites and patients to participate in studies which would further aid in the understanding and the complexity of this disease. The goal was to better understand which predictors defined the course of each breast cancer patient’s disease. This was done by conducting correlative science studies. These studies were done in a subset of patients. Immunohistochemical analyses, tumor RNA profiling, tissue microarray analysis, estradiol, estrone and estrone sulfate levels, pharmacogenetics and proteomics comprised these studies. This amendment also updated the protocol information concerning statistical analysis of patients who had received neo-adjuvant therapy prior to study entry. The approval of amendment 2 allowed for the entry of these patients. New information regarding European Union regulatory guidelines and the lack of theoretical justification for the use of traditional statistical analyses in conjunction with a complex dynamic allocation became known after the approval of amendment 2.
    25 Mar 2008
    Amendment 4 updated the procedures for the handling of the biological samples and the addition of an evaluation of disease status at Month 18. The steering committee added additional endocrine and proteomics sampling times to allow more flexibility for the sites and patients. Month 6, 18, or 24 were options. A maximum of two samples were required but when the samples were obtained was flexible. Since the exact timing of the pharmacogenetic sample was not critical, the steering committee broadened the time when the sample could be obtained. It could be obtained at either baseline, month 6, 12,18, or 24. The secondary objectives were updated to remove breast cancer specific survival since the current data collection forms did not specifically collect this information. Without the specific information collected, this endpoint could not be determined. Also, eliminated was the need to stratify by presence or absence of neo-adjuvant chemotherapy in the statistical analysis plan. Neo-adjuvant chemotherapy was not a stratification factor for the determination of the treatment assignment. There were very few patients in this category so this was of minimal interest. The formal process for handling protocol violations was added to the Procedures section of the protocol. Amendment 4 called for the completion of the study at 959 disease free survival (DFS) events and 5 years after the completion of enrollment. The event rate was lower than initially planned in the protocol, and the protocol was amended to extend the follow up period in order to continue the collection of the primary endpoint data. The study’s second interim analysis was conducted after the data cutoff of 21-Nov-2013. It was based on 704 DFS events.
    19 Dec 2013
    Amendment 5 was created to extend the follow up period to continue to collect events/endpoints. Amendment 5 was released to the countries and sites in January 2014. It was approved by several of the countries, but none of the patients were re-consented. Based on the Kaplan-Meier curve from the second interim analysis, the statistical team modeled that it would take until 2022 to reach the 959 DFS events, the trial’s primary endpoint. Considering that only approximately 1000 patients globally would be available forre-consenting and follow-up, the decision was made not to implement protocol amendment 5, which extended the follow-up period, and therefore terminate the trial early. Amendment 5 had been released, submitted, and approved in several countries and the global and local processes for early termination of the trial were implemented. No patients were re-consented nor were active participants in the extended follow-up period as part of Amendment 5.

    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.
    Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.
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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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