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    Clinical Trial Results:
    An open-label extension trial of the long-term safety of oral BIBF 1120 in patients with idiopathic pulmonary fibrosis (IPF)

    Summary
    EudraCT number
    		 2011-002766-21
    Trial protocol
    		 GR   PT   BE   ES   DE   FI   GB   CZ   IT   IE  
    Global end of trial date
    01 Feb 2021

    Results information
    Results version number
    		 v1
    This version publication date
    05 Feb 2022
    First version publication date
    05 Feb 2022
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    1199.33
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01619085
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Boehringer Ingelheim
    Sponsor organisation address
    Binger Strasse 173, Ingelheim am Rhein, Germany, 55216
    Public contact
    Boehringer Ingelheim Call Center, Boehringer Ingelheim, +1 8002430127, clintriage.rdg@boehringer-ingelheim.com
    Scientific contact
    Boehringer Ingelheim, Call Center, Boehringer Ingelheim, +1 18002430127, clintriage.rdg@boehringer-ingelheim.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    22 Feb 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Jul 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Feb 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the trial was to assess the long-term safety of oral nintedanib treatment in patients with IPF who had completed 52 weeks of treatment and the follow-up period of Phase III parent trial 1199.32 or 1199.34.
    Protection of trial subjects
    All patients were informed that they were free to withdraw their consent at any time during the trial without penalty and prejudice. The signed informed consent forms and any additional patient information were retained by the investigator as part of the trial records. Each patient received a copy of the signed informed consent form and any additional patient information. Patients were informed that their medical records could be examined by authorised monitors or Clinical Quality Assurance auditors of BI, members of the appropriate IEC/IRB, and regulatory authority inspectors. Patients were also informed that all medical information obtained during the course of the trial was considered confidential and used by BI in accordance with the local data protection law. Confidentiality of patient data was ensured by the use of depersonalised patient identification codes (patient numbers). In compliance with local legislation, trial sites in France did not collect information concerning patient race. The terms and conditions of the insurance cover were made available to the investigator and patients in the investigator site file (ISF).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Jul 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 22
    Country: Number of subjects enrolled
    Belgium: 15
    Country: Number of subjects enrolled
    Canada: 6
    Country: Number of subjects enrolled
    Chile: 9
    Country: Number of subjects enrolled
    China: 69
    Country: Number of subjects enrolled
    Czechia: 8
    Country: Number of subjects enrolled
    Finland: 9
    Country: Number of subjects enrolled
    France: 88
    Country: Number of subjects enrolled
    Germany: 72
    Country: Number of subjects enrolled
    Greece: 10
    Country: Number of subjects enrolled
    India: 14
    Country: Number of subjects enrolled
    Ireland: 1
    Country: Number of subjects enrolled
    Israel: 14
    Country: Number of subjects enrolled
    Italy: 63
    Country: Number of subjects enrolled
    Japan: 85
    Country: Number of subjects enrolled
    Korea, Republic of: 38
    Country: Number of subjects enrolled
    Mexico: 5
    Country: Number of subjects enrolled
    Netherlands: 15
    Country: Number of subjects enrolled
    Portugal: 12
    Country: Number of subjects enrolled
    Russian Federation: 2
    Country: Number of subjects enrolled
    Spain: 18
    Country: Number of subjects enrolled
    Turkey: 38
    Country: Number of subjects enrolled
    United Kingdom: 29
    Country: Number of subjects enrolled
    United States: 115
    Worldwide total number of subjects
    757
    EEA total number of subjects
    311
    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)
    273
    From 65 to 84 years
    477
    85 years and over
    7

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was a prospective, open-label extension trial in which patients with Idiopathic pulmonary fibrosis (IPF), who had completed 52 weeks of treatment and the follow-up period in the randomised, double-blind, placebo-controlled parent trials 1199.32/.34 and who needed access to nintedanib outside of the discontinued parent trials 1199.35/.187.

    Pre-assignment
    Screening details
    		 All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

    Period 1
    Period 1 title
    Period 1 - 1199.32/.34/.35/.187
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Total (1199.32/.34)
    Arm description
    		 This group included patients originated from parent trials 1199.32/.34. For patients participated in parent trials 1199.32/.34, they were to receive continuous dosing of soft gelatin capsules of nintedanib (orally) 150 milligrams (mg) twice daily (bid) in this study unless they had reduced the dose to 100 mg bid trial drug (nintedanib or placebo) in the parent trial; patients receiving 100 mg bid trial drug at the end of the parent trial could receive either nintedanib 100 mg bid or nintedanib 150 mg bid in this study. The daily nintedanib dose for such patients was decided at baseline visit based on discussion between the patient and the investigator. After unblinding of the parent trials, patients randomized to placebo in parent trials, who reduced the dose to 100 mg bid in the parent trial, could increase the dose to nintedanib 150 mg bid in this study. The dose could also be increased to 150 mg at a later time point if medically justified in this study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nintedanib
    Investigational medicinal product code
    BIBF 1120
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    Continuous dosing of 100 milligrams or 150 milligrams of soft gelatin capsules of nintedanib (orally) twice daily. In this study, patients were treated with nintedanib until they met one of the discontinuation criteria. Potential reasons for treatment discontinuation include impaired liver function, recurrence of diarrhoea, and progression of idiopathic pulmonary fibrosis.

    Arm title
    		 Total (1199.35/.187)
    Arm description
    		 This group included patients originated from parent trials 1199.35/.187. For patients participated in parent trials 1199.35/.187 (1199.35: open label; 1199.187: randomized placebo-control): patients were to receive the same daily dosage of soft gelatin capsules of nintedanib (orally) as in the parent trials (100 mg bid or 150 mg bid) in this study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nintedanib
    Investigational medicinal product code
    BIBF 1120
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    Continuous dosing of 100 milligrams or 150 milligrams of soft gelatin capsules of nintedanib (orally) twice daily. In this study, patients were treated with nintedanib until they met one of the discontinuation criteria. Potential reasons for treatment discontinuation include impaired liver function, recurrence of diarrhoea, and progression of idiopathic pulmonary fibrosis.

    Number of subjects in period 1
    		Total (1199.32/.34) Total (1199.35/.187)
    Started
    735
    17
    Treated
    734
    17
    Completed
    734
    17
    Not completed
    1
    0
         Not treated
    1
    -
    Period 2
    Period 2 title
    Period 2 - 1199.32/.34 only
    Is this the baseline period?
    		 Yes [1]
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Total (1199.32/.34)
    Arm description
    		 This group included patients originated from parent trials 1199.32/.34. For patients participated in parent trials 1199.32/.34, they were to receive continuous dosing of soft gelatin capsules of nintedanib (orally) 150 milligrams (mg) twice daily (bid) in this study unless they had reduced the dose to 100 mg bid trial drug (nintedanib or placebo) in the parent trial; patients receiving 100 mg bid trial drug at the end of the parent trial could receive either nintedanib 100 mg bid or nintedanib 150 mg bid in this study. The daily nintedanib dose for such patients was decided at baseline visit based on discussion between the patient and the investigator. After unblinding of the parent trials, patients randomized to placebo in parent trials, who reduced the dose to 100 mg bid in the parent trial, could increase the dose to nintedanib 150 mg bid in this study. The dose could also be increased to 150 mg at a later time point if medically justified in this study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nintedanib
    Investigational medicinal product code
    BIBF 1120
    Other name
    Pharmaceutical forms
    Capsule, soft
    Routes of administration
    Oral use
    Dosage and administration details
    Continuous dosing of 100 milligrams or 150 milligrams of soft gelatin capsules of nintedanib (orally) twice daily. In this study, patients were treated with nintedanib until they met one of the discontinuation criteria. Potential reasons for treatment discontinuation include impaired liver function, recurrence of diarrhoea, and progression of idiopathic pulmonary fibrosis.

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: The group in Period 2 was planned in the protocol using to report the baseline characteristics.
    Number of subjects in period 2 [2] [3]
    		Total (1199.32/.34)
    Started
    734
    Completed
    210
    Not completed
    524
         Adverse event, serious fatal
    145
         Consent withdrawn by subject
    45
         Adverse event, non-fatal
    231
         Other than specified
    96
         Lost to follow-up
    3
         Protocol deviation
    4
    Notes
    [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Baseline characteristics are based on patients who were randomized after successfully completing the screening period and received at least one of the trial medication.
    [3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Period 2 is created to indicate the group used for reporting baseline characteristics and does not reflect the actual chronological order.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Total (1199.32/.34)
    Reporting group description
    		 This group included patients originated from parent trials 1199.32/.34. For patients participated in parent trials 1199.32/.34, they were to receive continuous dosing of soft gelatin capsules of nintedanib (orally) 150 milligrams (mg) twice daily (bid) in this study unless they had reduced the dose to 100 mg bid trial drug (nintedanib or placebo) in the parent trial; patients receiving 100 mg bid trial drug at the end of the parent trial could receive either nintedanib 100 mg bid or nintedanib 150 mg bid in this study. The daily nintedanib dose for such patients was decided at baseline visit based on discussion between the patient and the investigator. After unblinding of the parent trials, patients randomized to placebo in parent trials, who reduced the dose to 100 mg bid in the parent trial, could increase the dose to nintedanib 150 mg bid in this study. The dose could also be increased to 150 mg at a later time point if medically justified in this study.

    Reporting group values
    		 Total (1199.32/.34) Total
    Number of subjects
    		 734 734
    Age categorical
    Treated set (TS): The data set consisted of all patients who were dispensed trial medication and were documented to have taken at least one dose, and had participated in 1199.32/.34 parent trials.
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 262 262
        From 65-84 years
    		 465 465
        85 years and over
    		 7 7
    Age Continuous
    Treated set (TS): The data set consisted of all patients who were dispensed trial medication and were documented to have taken at least one dose, and had participated in 1199.32/.34 parent trials.
    Units: years
        arithmetic mean (standard deviation)
    		 67.2 ± 7.8 -
    Sex: Female, Male
    Treated set (TS): The data set consisted of all patients who were dispensed trial medication and were documented to have taken at least one dose, and had participated in 1199.32/.34 parent trials.
    Units: Participants
        Female
    		 147 147
        Male
    		 587 587
    Race
    Treated set (TS): The data set consisted of all patients who were dispensed trial medication and were documented to have taken at least one dose, and had participated in 1199.32/.34 parent trials.
    Units: Subjects
        American Indian or Alaska Native
    		 1 1
        Asian
    		 214 214
        Native Hawaiian or Other Pacific Islander
    		 0 0
        Black or African American
    		 2 2
        White
    		 431 431
        More than one race
    		 0 0
        Unknown or Not Reported
    		 86 86

    End points

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    End points reporting groups
    Reporting group title
    Total (1199.32/.34)
    Reporting group description
    		 This group included patients originated from parent trials 1199.32/.34. For patients participated in parent trials 1199.32/.34, they were to receive continuous dosing of soft gelatin capsules of nintedanib (orally) 150 milligrams (mg) twice daily (bid) in this study unless they had reduced the dose to 100 mg bid trial drug (nintedanib or placebo) in the parent trial; patients receiving 100 mg bid trial drug at the end of the parent trial could receive either nintedanib 100 mg bid or nintedanib 150 mg bid in this study. The daily nintedanib dose for such patients was decided at baseline visit based on discussion between the patient and the investigator. After unblinding of the parent trials, patients randomized to placebo in parent trials, who reduced the dose to 100 mg bid in the parent trial, could increase the dose to nintedanib 150 mg bid in this study. The dose could also be increased to 150 mg at a later time point if medically justified in this study.

    Reporting group title
    Total (1199.35/.187)
    Reporting group description
    		 This group included patients originated from parent trials 1199.35/.187. For patients participated in parent trials 1199.35/.187 (1199.35: open label; 1199.187: randomized placebo-control): patients were to receive the same daily dosage of soft gelatin capsules of nintedanib (orally) as in the parent trials (100 mg bid or 150 mg bid) in this study.
    Reporting group title
    Total (1199.32/.34)
    Reporting group description
    		 This group included patients originated from parent trials 1199.32/.34. For patients participated in parent trials 1199.32/.34, they were to receive continuous dosing of soft gelatin capsules of nintedanib (orally) 150 milligrams (mg) twice daily (bid) in this study unless they had reduced the dose to 100 mg bid trial drug (nintedanib or placebo) in the parent trial; patients receiving 100 mg bid trial drug at the end of the parent trial could receive either nintedanib 100 mg bid or nintedanib 150 mg bid in this study. The daily nintedanib dose for such patients was decided at baseline visit based on discussion between the patient and the investigator. After unblinding of the parent trials, patients randomized to placebo in parent trials, who reduced the dose to 100 mg bid in the parent trial, could increase the dose to nintedanib 150 mg bid in this study. The dose could also be increased to 150 mg at a later time point if medically justified in this study.

    Primary: Incidence of Adverse Events (AEs)

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    End point title
    		 Incidence of Adverse Events (AEs) [1]
    End point description
    This is the measure for percentage of patients with adverse events (AEs) observed during the trial. The incidence of adverse events (% of patients) over the course of the trial, including the incidence of serious AEs, AEs leading to discontinuation, and fatal AEs are presented. Treated set (TS): The data set consisted of all patients who were dispensed trial medication and were documented to have taken at least one dose, and had participated in 1199.32/.34 parent trials.
    End point type
    Primary
    End point timeframe
    From first drug administration until end of treatment period + 28 days, in total up to 56.3 months plus 28 days.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis were tested.
    End point values
    		 Total (1199.32/.34)
    Number of subjects analysed
    734
    Units: Percentage of patients (%)
    number (not applicable)
        Any AEs
    98.5
        AEs leading to discontinuation of trial drug
    42.6
        Serious AEs
    68.9
        Fatal AEs
    23.8
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first drug administration until 28 days after the last drug administration, up to 7.5 years.
    Adverse event reporting additional description
    Treated set (TS) [and TS35; TS187]: The data set consisted of all patients who were dispensed trial medication and were documented to have taken at least one dose, and had participated in 1199.32/.34 [in 1199.35 for TS35; in 1199.187 for TS187] parent trials. TS (from .32/.34), TS35 (from .35), and TS187 (from .187) are all used to report the AEs.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Placebo (.32/.34)
    Reporting group description
    		 Patients in this group are those who were randomized to placebo arm in parent trials 1199.32/.34 and were treated with 100 milligrams or 150 milligrams of nintedanib orally twice daily in this study.

    Reporting group title
    Placebo (.35/.187)
    Reporting group description
    		 Patients in this group are those who were randomized to placebo arm in parent trial 1199.187 and were treated with 150 milligrams or 100 milligrams of nintedanib twice daily in this study.

    Reporting group title
    Total (1199.32/.34)
    Reporting group description
    		 This group included patients originated from parent trials 1199.32/.34. For patients participated in parent trials 1199.32/.34 (both were randomized, placebo-controlled): patients were to receive continuous dosing of soft gelatin capsules of nintedanib (orally) 150 milligrams (mg) twice daily (bid) in this study unless they had reduced the dose to 100 mg bid trial drug (nintedanib or placebo) in the parent trial; patients receiving 100 mg bid trial drug at the end of the parent trial could receive either nintedanib 100 mg bid or nintedanib 150 mg bid in this study. After unblinding of the parent trials, patients randomized to placebo in parent trials, who reduced the dose to 100 mg bid in the parent trial, could increase the dose to nintedanib 150 mg bid in this study. The dose could also be increased to 150 mg at a later time point if medically justified in this study.

    Reporting group title
    Nintedanib 150 bid (.32/.34)
    Reporting group description
    		 Patients in this group are those who were randomized to 150 milligrams nintedanib twice daily (bid) arm in the parent trials 1199.32/.34 and were treated with 100 milligrams or 150 milligrams of nintedanib orally twice daily in this study.

    Reporting group title
    Nintedanib 100 bid (.35/.187)
    Reporting group description
    		 Patients in this group are those who were participated in the parent trial 1199.35 and were treated with 100 milligrams of nintedanib twice daily (bid) in this study.

    Reporting group title
    Total (.32/.34/.35/.187)
    Reporting group description
    		 For those from parent trials 1199.32/.34 (both were randomized, placebo-controlled): patients received continuous dosing of soft gelatin capsules of nintedanib (orally) 150 milligrams (mg) twice daily (bid) in this study unless they had reduced the dose to 100 mg bid trial drug (nintedanib (nint.) or placebo) in the parent trial; patients receiving 100 mg bid trial drug at the end of the parent trial could receive either nint. 100 mg bid or nint. 150 mg bid in this study. After unblinding of the parent trials, patients randomized to placebo, who reduced the dose to 100 mg bid, could increase the dose to nint. 150 mg bid in this study. The dose could also be increased to 150 mg at a later time point if medically justified in this study. For those from parent trials 1199.35/.187 (.35: open label; .187: randomized placebo-control): patients received the same daily dosage of soft gelatin capsules of nint. (orally) as in the parent trials (100 mg bid or 150 mg bid) in this study.

    Reporting group title
    Total (.35/.187)
    Reporting group description
    		 This group included patients originated from parent trials 1199.35/.187. For patients participated in parent trials 1199.35/.187, they were to receive the same daily dosage of soft gelatin capsules of nintedanib (orally) as in the parent trials (100 milligrams (mg) twice daily (bid) or 150 mg bid) in this study.

    Reporting group title
    Nintedanib 150 bid (.35/.187)
    Reporting group description
    		 Patients in this group are those who were treated with 150 milligrams (mg) of nintedanib twice daily (bid) in this study and were participated in parent trial 1199.35 plus those who were randomized to 150 mg nintedanib bid arm in the parent trial 1199.187 and were treated with 150 mg or 100 mg nintedanib bid in this study.

    Serious adverse events
    		 Placebo (.32/.34) Placebo (.35/.187) Total (1199.32/.34) Nintedanib 150 bid (.32/.34) Nintedanib 100 bid (.35/.187) Total (.32/.34/.35/.187) Total (.35/.187) Nintedanib 150 bid (.35/.187)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    208 / 304 (68.42%)
    0 / 7 (0.00%)
    509 / 734 (69.35%)
    301 / 430 (70.00%)
    0 / 2 (0.00%)
    510 / 751 (67.91%)
    1 / 17 (5.88%)
    1 / 8 (12.50%)
         number of deaths (all causes)
    78
    0
    182
    104
    0
    182
    0
    0
         number of deaths resulting from adverse events
    1
    0
    1
    0
    0
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    8 / 734 (1.09%)
    6 / 430 (1.40%)
    0 / 2 (0.00%)
    8 / 751 (1.07%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 9
    0 / 7
    0 / 0
    0 / 9
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer recurrent
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder neoplasm
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bowen's disease
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 3
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholangiocarcinoma
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    4 / 304 (1.32%)
    0 / 7 (0.00%)
    7 / 734 (0.95%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    7 / 751 (0.93%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 7
    0 / 3
    0 / 0
    0 / 7
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    4 / 304 (1.32%)
    0 / 7 (0.00%)
    13 / 734 (1.77%)
    9 / 430 (2.09%)
    0 / 2 (0.00%)
    13 / 751 (1.73%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 13
    0 / 9
    0 / 0
    0 / 13
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Metastases to eye
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Metastatic squamous cell carcinoma
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine carcinoma
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural neoplasm
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    5 / 734 (0.68%)
    4 / 430 (0.93%)
    0 / 2 (0.00%)
    5 / 751 (0.67%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 5
    0 / 4
    0 / 0
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostatic adenoma
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sarcoma
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    6 / 734 (0.82%)
    4 / 430 (0.93%)
    0 / 2 (0.00%)
    6 / 751 (0.80%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 6
    0 / 4
    0 / 0
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 2
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    Small intestine carcinoma
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    4 / 304 (1.32%)
    0 / 7 (0.00%)
    8 / 734 (1.09%)
    4 / 430 (0.93%)
    0 / 2 (0.00%)
    8 / 751 (1.07%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 10
    0 / 5
    0 / 0
    0 / 10
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 5
    1 / 4
    0 / 0
    1 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour of ampulla of Vater
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cutaneous T-cell lymphoma
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Cyanosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 2
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial thrombosis
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 4
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Surgical and medical procedures
    Knee arthroplasty
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transurethral prostatectomy
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    1 / 2
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    11 / 734 (1.50%)
    8 / 430 (1.86%)
    0 / 2 (0.00%)
    11 / 751 (1.46%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 11
    0 / 8
    0 / 0
    0 / 11
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Complication associated with device
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Condition aggravated
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 2
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 3
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 3
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
    0 / 2
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
    0 / 2
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 5
    0 / 4
    0 / 0
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    5 / 734 (0.68%)
    4 / 430 (0.93%)
    0 / 2 (0.00%)
    5 / 751 (0.67%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 5
    0 / 4
    0 / 0
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 5
    0 / 4
    0 / 0
    0 / 5
    0 / 0
    0 / 0
    Vascular stent stenosis
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    5 / 734 (0.68%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    5 / 751 (0.67%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 5
    0 / 2
    0 / 0
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital prolapse
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    4 / 304 (1.32%)
    0 / 7 (0.00%)
    15 / 734 (2.04%)
    11 / 430 (2.56%)
    0 / 2 (0.00%)
    15 / 751 (2.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 17
    0 / 12
    0 / 0
    0 / 17
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 8
    0 / 6
    0 / 0
    0 / 8
    0 / 0
    0 / 0
    Bronchopleural fistula
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic respiratory failure
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    5 / 734 (0.68%)
    4 / 430 (0.93%)
    0 / 2 (0.00%)
    5 / 751 (0.67%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 5
    0 / 4
    0 / 0
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    16 / 304 (5.26%)
    0 / 7 (0.00%)
    38 / 734 (5.18%)
    22 / 430 (5.12%)
    0 / 2 (0.00%)
    38 / 751 (5.06%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 0
    0 / 46
    0 / 28
    0 / 0
    0 / 46
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 5
    0 / 0
    0 / 8
    0 / 3
    0 / 0
    0 / 8
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 3
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
    0 / 2
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Hypercapnia
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    9 / 304 (2.96%)
    0 / 7 (0.00%)
    13 / 734 (1.77%)
    4 / 430 (0.93%)
    0 / 2 (0.00%)
    13 / 751 (1.73%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 0
    0 / 14
    0 / 5
    0 / 0
    0 / 14
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 2
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    64 / 304 (21.05%)
    0 / 7 (0.00%)
    153 / 734 (20.84%)
    89 / 430 (20.70%)
    0 / 2 (0.00%)
    153 / 751 (20.37%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 70
    0 / 0
    1 / 170
    0 / 100
    0 / 0
    1 / 170
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 28
    0 / 0
    1 / 57
    0 / 29
    0 / 0
    1 / 57
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    10 / 734 (1.36%)
    7 / 430 (1.63%)
    0 / 2 (0.00%)
    10 / 751 (1.33%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 10
    0 / 7
    0 / 0
    0 / 10
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 3
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
    0 / 2
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Nasal polyps
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumomediastinum
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    6 / 304 (1.97%)
    0 / 7 (0.00%)
    15 / 734 (2.04%)
    9 / 430 (2.09%)
    0 / 2 (0.00%)
    15 / 751 (2.00%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
    0 / 15
    0 / 9
    0 / 0
    0 / 15
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Productive cough
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pulmonary arterial hypertension
         subjects affected / exposed
    5 / 304 (1.64%)
    0 / 7 (0.00%)
    11 / 734 (1.50%)
    6 / 430 (1.40%)
    0 / 2 (0.00%)
    11 / 751 (1.46%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 11
    0 / 6
    0 / 0
    0 / 11
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    11 / 304 (3.62%)
    0 / 7 (0.00%)
    17 / 734 (2.32%)
    6 / 430 (1.40%)
    0 / 2 (0.00%)
    17 / 751 (2.26%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 0
    0 / 17
    0 / 6
    0 / 0
    0 / 17
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 5
    0 / 0
    0 / 5
    0 / 0
    0 / 0
    0 / 5
    0 / 0
    0 / 0
    Pulmonary fibrosis
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    12 / 734 (1.63%)
    9 / 430 (2.09%)
    0 / 2 (0.00%)
    12 / 751 (1.60%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 13
    0 / 9
    0 / 0
    0 / 13
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pulmonary granuloma
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    22 / 304 (7.24%)
    0 / 7 (0.00%)
    48 / 734 (6.54%)
    26 / 430 (6.05%)
    0 / 2 (0.00%)
    48 / 751 (6.39%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 25
    0 / 0
    0 / 54
    0 / 29
    0 / 0
    0 / 54
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Pulmonary infarction
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
    0 / 2
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory acidosis
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    9 / 304 (2.96%)
    0 / 7 (0.00%)
    35 / 734 (4.77%)
    26 / 430 (6.05%)
    0 / 2 (0.00%)
    35 / 751 (4.66%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 0
    0 / 44
    0 / 34
    0 / 0
    0 / 44
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 6
    0 / 0
    0 / 22
    0 / 16
    0 / 0
    0 / 22
    0 / 0
    0 / 0
    Respiratory tract haemorrhage
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood urea increased
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Body temperature increased
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibrin D dimer increased
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glycosylated haemoglobin increased
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    5 / 734 (0.68%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    5 / 751 (0.67%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    3 / 5
    1 / 3
    0 / 0
    3 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Imaging procedure abnormal
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Carbon monoxide poisoning
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest injury
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    4 / 304 (1.32%)
    0 / 7 (0.00%)
    6 / 734 (0.82%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    6 / 751 (0.80%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 6
    0 / 2
    0 / 0
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    4 / 304 (1.32%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypobarism
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative delirium
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiation pneumonitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 4
    0 / 1
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 2
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 2
    0 / 1
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural fever
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Porokeratosis
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 2
    0 / 1
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    6 / 734 (0.82%)
    5 / 430 (1.16%)
    0 / 2 (0.00%)
    6 / 751 (0.80%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 6
    1 / 5
    0 / 0
    1 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 2
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    5 / 734 (0.68%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    5 / 751 (0.67%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 5
    0 / 2
    0 / 0
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    6 / 304 (1.97%)
    0 / 7 (0.00%)
    9 / 734 (1.23%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    9 / 751 (1.20%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
    0 / 9
    0 / 3
    0 / 0
    0 / 9
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 4
    0 / 1
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    6 / 304 (1.97%)
    0 / 7 (0.00%)
    12 / 734 (1.63%)
    6 / 430 (1.40%)
    0 / 2 (0.00%)
    12 / 751 (1.60%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
    0 / 15
    0 / 9
    0 / 0
    0 / 15
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 6
    0 / 3
    0 / 0
    0 / 6
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    7 / 734 (0.95%)
    6 / 430 (1.40%)
    0 / 2 (0.00%)
    7 / 751 (0.93%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 9
    0 / 8
    0 / 0
    0 / 9
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Conduction disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cor pulmonale
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    8 / 734 (1.09%)
    7 / 430 (1.63%)
    0 / 2 (0.00%)
    8 / 751 (1.07%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 8
    0 / 7
    0 / 0
    0 / 8
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Cor pulmonale chronic
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    9 / 734 (1.23%)
    7 / 430 (1.63%)
    0 / 2 (0.00%)
    9 / 751 (1.20%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 9
    0 / 7
    0 / 0
    0 / 9
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    6 / 734 (0.82%)
    4 / 430 (0.93%)
    0 / 2 (0.00%)
    6 / 751 (0.80%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 6
    0 / 4
    0 / 0
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 4
    0 / 3
    0 / 0
    1 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    5 / 734 (0.68%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    5 / 751 (0.67%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    1 / 5
    0 / 2
    0 / 0
    1 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    5 / 734 (0.68%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    5 / 751 (0.67%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 5
    0 / 2
    0 / 0
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prosthetic cardiac valve thrombosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain hypoxia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral artery occlusion
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral artery stenosis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral atrophy
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
    1 / 3
    0 / 0
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    9 / 734 (1.23%)
    6 / 430 (1.40%)
    0 / 2 (0.00%)
    9 / 751 (1.20%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    1 / 9
    1 / 6
    0 / 0
    1 / 9
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    5 / 734 (0.68%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    5 / 751 (0.67%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    2 / 5
    1 / 3
    0 / 0
    2 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
    1 / 1
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deafness unilateral
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden hearing loss
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vestibular disorder
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Amaurosis fugax
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blindness transient
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
    0 / 2
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dry age-related macular degeneration
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Optic ischaemic neuropathy
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Panophthalmitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periorbital fat herniation
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Posterior capsule opacification
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Retinal artery occlusion
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal vein occlusion
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vision blurred
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 304 (0.99%)
    0 / 7 (0.00%)
    3 / 734 (0.41%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    3 / 751 (0.40%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    1 / 3
    0 / 0
    0 / 0
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal haemorrhage
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    2 / 430 (0.47%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    5 / 304 (1.64%)
    0 / 7 (0.00%)
    10 / 734 (1.36%)
    5 / 430 (1.16%)
    0 / 2 (0.00%)
    10 / 751 (1.33%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    3 / 5
    0 / 0
    8 / 10
    5 / 5
    0 / 0
    8 / 10
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    2 / 304 (0.66%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erosive oesophagitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 3
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 4
    1 / 3
    0 / 0
    1 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 2
    1 / 1
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    4 / 304 (1.32%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia, obstructive
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    0 / 430 (0.00%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstruction gastric
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic pseudocyst
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    4 / 734 (0.54%)
    3 / 430 (0.70%)
    0 / 2 (0.00%)
    4 / 751 (0.53%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 4
    1 / 3
    0 / 0
    2 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis necrotising
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Protein-losing gastroenteropathy
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    2 / 751 (0.27%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
    1 / 1
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 304 (0.00%)
    0 / 7 (0.00%)
    1 / 734 (0.14%)
    1 / 430 (0.23%)
    0 / 2 (0.00%)
    1 / 751 (0.13%)
    0 / 17 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 304 (0.33%)
    0 / 7 (0.00%)
    2 / 734 (0.27%)