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    Clinical Trial Results:
    A Multinational Multicenter Study to Assess the Effects of Oral Sildenafil on Mortality in Adults With Pulmonary Arterial Hypertension (PAH)

    Summary
    EudraCT number
    		 2013-004362-34
    Trial protocol
    		 SE   AT   BE   DE   ES   CZ   RO   PL   GR   NL   PT   HR   LV  
    Global end of trial date
    26 Feb 2021

    Results information
    Results version number
    		 v2(current)
    This version publication date
    17 Jul 2022
    First version publication date
    18 Apr 2022
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    A1481324
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02060487
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Viatris Specialty LLC
    Sponsor organisation address
    3711 Collins Ferry Road, Morgantown, United States, WV 26505
    Public contact
    Global Clinical Operations Lead, Meda Pharma GmbH & Co. KG (A Viatris company), Baerbel.Fingerhut@viatris.com
    Scientific contact
    Global Clinical Operations Lead, Meda Pharma GmbH & Co. KG (A Viatris company), Baerbel.Fingerhut@viatris.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
    16 Jul 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Feb 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To test for the non-inferiority of sildenafil 80 milligrams (mg) versus 5 mg for mortality; mortality rate with the 80 mg dose was to be no worse than double the mortality rate for the 5 mg dose.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Sep 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 7
    Country: Number of subjects enrolled
    Belgium: 1
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 13
    Country: Number of subjects enrolled
    Croatia: 10
    Country: Number of subjects enrolled
    Czechia: 37
    Country: Number of subjects enrolled
    Germany: 34
    Country: Number of subjects enrolled
    Greece: 14
    Country: Number of subjects enrolled
    Hong Kong: 3
    Country: Number of subjects enrolled
    Israel: 1
    Country: Number of subjects enrolled
    Latvia: 20
    Country: Number of subjects enrolled
    Malaysia: 17
    Country: Number of subjects enrolled
    Mexico: 9
    Country: Number of subjects enrolled
    Poland: 1
    Country: Number of subjects enrolled
    Romania: 29
    Country: Number of subjects enrolled
    Russian Federation: 49
    Country: Number of subjects enrolled
    Serbia: 14
    Country: Number of subjects enrolled
    Singapore: 4
    Country: Number of subjects enrolled
    South Africa: 3
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    Thailand: 28
    Country: Number of subjects enrolled
    Turkey: 9
    Country: Number of subjects enrolled
    Ukraine: 68
    Country: Number of subjects enrolled
    United States: 10
    Worldwide total number of subjects
    385
    EEA total number of subjects
    150
    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)
    291
    From 65 to 84 years
    94
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This was a randomised, double-blind, parallel-group, multinational and multicenter study to assess the effects of oral sildenafil on mortality in adult subjects with pulmonary arterial hypertension (PAH). The study was conducted at 68 active sites in 23 countries.

    Pre-assignment
    Screening details
    		 A total of 445 subjects were screened of which, 47 subjects failed screening and 13 subjects were neither screen failures nor randomised. A total of 385 subjects were actually enrolled into the study and assigned to a study treatment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sildenafil 5 mg
    Arm description
    		 Subjects received a single tablet of sildenafil at a dose of 5 milligram (mg) along with two tablets of placebo matching 20 mg and 80 mg sildenafil orally thrice daily (TID) until discontinuation of study treatment or end of study. The maximum duration of study treatment was 2080 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sildenafil citrate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a single tablet of sildenafil at a dose of 5 mg orally thrice daily (TID).

    Investigational medicinal product name
    80 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a single tablet of placebo at a dose of 80 mg orally TID.

    Investigational medicinal product name
    20 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a single tablet of placebo at a dose of 20 mg orally TID.

    Arm title
    		 Sildenafil 20 mg
    Arm description
    		 Subjects received a single tablet of sildenafil at a dose of 20 mg along with two tablets of placebo matching 5 mg and 80 mg sildenafil orally TID until discontinuation of study treatment or end of study. The maximum duration of study treatment was 1984 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sildenafil citrate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a single tablet of sildenafil at a dose of 20 mg orally TID

    Investigational medicinal product name
    80 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a single tablet of placebo at a dose of 80 mg orally TID

    Investigational medicinal product name
    5 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a single tablet of placebo at a dose of 5 mg orally TID.

    Arm title
    		 Sildenafil 80 mg
    Arm description
    		 Subjects received a single tablet of sildenafil at a dose of 20 mg along with two tablets of placebo matching 5 mg and 80 mg sildenafil orally TID on day 1 for 2 weeks and then titrated up to 80 mg at week 2 along with two tablets of placebo matching 5 mg and 20 mg sildenafil orally TID until discontinuation of study treatment or end of study. The maximum duration of study treatment was 2073 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    5 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a single tablet of placebo at a dose of 5 mg orally TID.

    Investigational medicinal product name
    Sildenafil citrate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a single tablet of sildenafil at a dose of 80 mg orally TID

    Investigational medicinal product name
    20 mg matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a single tablet of placebo at a dose of 5 mg orally TID.

    Number of subjects in period 1
    		Sildenafil 5 mg Sildenafil 20 mg Sildenafil 80 mg
    Started
    129
    128
    128
    Completed
    0
    0
    0
    Not completed
    129
    128
    128
         Consent withdrawn by subject
    3
    10
    4
         Study Terminated By Sponsor
    87
    89
    100
         Adverse event, non-fatal
    -
    -
    1
         Death
    34
    25
    19
         Unspecified
    1
    2
    1
         Lost to follow-up
    3
    -
    2
         Randomised in error
    1
    -
    -
         Lack of efficacy
    -
    1
    -
         Protocol deviation
    -
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Sildenafil 5 mg
    Reporting group description
    		 Subjects received a single tablet of sildenafil at a dose of 5 milligram (mg) along with two tablets of placebo matching 20 mg and 80 mg sildenafil orally thrice daily (TID) until discontinuation of study treatment or end of study. The maximum duration of study treatment was 2080 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.

    Reporting group title
    Sildenafil 20 mg
    Reporting group description
    		 Subjects received a single tablet of sildenafil at a dose of 20 mg along with two tablets of placebo matching 5 mg and 80 mg sildenafil orally TID until discontinuation of study treatment or end of study. The maximum duration of study treatment was 1984 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.

    Reporting group title
    Sildenafil 80 mg
    Reporting group description
    		 Subjects received a single tablet of sildenafil at a dose of 20 mg along with two tablets of placebo matching 5 mg and 80 mg sildenafil orally TID on day 1 for 2 weeks and then titrated up to 80 mg at week 2 along with two tablets of placebo matching 5 mg and 20 mg sildenafil orally TID until discontinuation of study treatment or end of study. The maximum duration of study treatment was 2073 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.

    Reporting group values
    		 Sildenafil 5 mg Sildenafil 20 mg Sildenafil 80 mg Total
    Number of subjects
    		 129 128 128 385
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 98 98 95 291
        From 65-84 years
    		 31 30 33 94
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 51.4 ± 15.02 51.2 ± 15.81 52.1 ± 14.72 -
    Sex: Female, Male
    Units: Subjects
        Female
    		 97 102 98 297
        Male
    		 32 26 30 88
    Race
    Units: Subjects
        Asian
    		 23 14 19 56
        White
    		 104 113 108 325
        Unknown or Not Reported
    		 2 1 1 4
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 5 4 3 12
        Not Hispanic or Latino
    		 124 124 125 373

    End points

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    End points reporting groups
    Reporting group title
    Sildenafil 5 mg
    Reporting group description
    		 Subjects received a single tablet of sildenafil at a dose of 5 milligram (mg) along with two tablets of placebo matching 20 mg and 80 mg sildenafil orally thrice daily (TID) until discontinuation of study treatment or end of study. The maximum duration of study treatment was 2080 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.

    Reporting group title
    Sildenafil 20 mg
    Reporting group description
    		 Subjects received a single tablet of sildenafil at a dose of 20 mg along with two tablets of placebo matching 5 mg and 80 mg sildenafil orally TID until discontinuation of study treatment or end of study. The maximum duration of study treatment was 1984 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.

    Reporting group title
    Sildenafil 80 mg
    Reporting group description
    		 Subjects received a single tablet of sildenafil at a dose of 20 mg along with two tablets of placebo matching 5 mg and 80 mg sildenafil orally TID on day 1 for 2 weeks and then titrated up to 80 mg at week 2 along with two tablets of placebo matching 5 mg and 20 mg sildenafil orally TID until discontinuation of study treatment or end of study. The maximum duration of study treatment was 2073 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.

    Primary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    In this end point number of deaths during the study were reported. The intent-to-treat population (ITT) included all randomised subjects treated with study treatment.
    End point type
    Primary
    End point timeframe
    Day 1 of study treatment up to date of death (within a maximum duration of 2102 days)
    End point values
    		 Sildenafil 5 mg Sildenafil 20 mg Sildenafil 80 mg
    Number of subjects analysed
    129
    128
    128
    Units: Subjects
    34
    25
    19
    Statistical analysis title
    		 Sildenafil 20 mg versus Sildenafil 5 mg TID
    Statistical analysis description
    Hazard ratio estimated from the Proportional Hazards model, stratified by actual previous PAH treatment and etiology of PAH.
    Comparison groups
    Sildenafil 5 mg v Sildenafil 20 mg
    Number of subjects included in analysis
    257
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.68
    Confidence interval
         level
    		 99.7%
         sides
    2-sided
         lower limit
    		 0.31
         upper limit
    		 1.49
    Notes
    [1] - Non-inferiority of sildenafil 20 mg TID versus sildenafil 5 mg TID was to be concluded if the upper limit of the 99.7% confidence interval (CI) for hazard ratio (HR) was less than 2.
    Statistical analysis title
    		 Sildenafil 80 mg versus Sildenafil 5 mg TID
    Statistical analysis description
    Hazard ratio estimated from the Proportional Hazards model, stratified by actual previous PAH treatment and etiology of PAH.
    Comparison groups
    Sildenafil 5 mg v Sildenafil 80 mg
    Number of subjects included in analysis
    257
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.51
    Confidence interval
         level
    		 99.7%
         sides
    2-sided
         lower limit
    		 0.22
         upper limit
    		 1.21
    Notes
    [2] - Non-inferiority of sildenafil 80 mg TID vs. sildenafil 5 mg TID was to be concluded if the upper limit of the 99.7% CI for HR was less than 2.
    Statistical analysis title
    		 Sildenafil 80 mg versus Sildenafil 20 mg TID
    Statistical analysis description
    Hazard ratio estimated from the Proportional Hazards model, stratified by actual previous PAH treatment and etiology of PAH.
    Comparison groups
    Sildenafil 20 mg v Sildenafil 80 mg
    Number of subjects included in analysis
    256
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.74
    Confidence interval
         level
    		 99.7%
         sides
    2-sided
         lower limit
    		 0.3
         upper limit
    		 1.84
    Notes
    [3] - Non-inferiority of sildenafil 80 mg TID vs. sildenafil 20 mg TID was to be concluded if the upper limit of the 99.7% CI for HR is less than 2.

    Secondary: Number of Subjects With Clinical Worsening Events

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    End point title
    		 Number of Subjects With Clinical Worsening Events
    End point description
    Clinical worsening was defined as all-cause mortality, non-elective hospital stay for worsening pulmonary arterial hypertension (PAH) (including but not limited to right heart failure [RHF], initiation of intravenous (IV) prostanoids, lung transplantation, or septostomy) or disease progression. Disease progression was defined as a reduction from baseline in the 6-Minute Walk Distance (6MWD) test by 15% and worsening functional class from baseline, both confirmed by second test within 2 weeks of study treatment. ITT population included all randomised subjects treated with study treatment.
    End point type
    Secondary
    End point timeframe
    Day 1 of study treatment up to date of clinical worsening event (within a maximum duration of 2080 days)
    End point values
    		 Sildenafil 5 mg Sildenafil 20 mg Sildenafil 80 mg
    Number of subjects analysed
    129
    128
    128
    Units: Subjects
    52
    36
    28
    Statistical analysis title
    		 Sildenafil 20 mg versus Sildenafil 5 mg TID
    Statistical analysis description
    Hazard ratio estimated from the Proportional Hazards model, stratified by actual previous PAH treatment and etiology of PAH.
    Comparison groups
    Sildenafil 5 mg v Sildenafil 20 mg
    Number of subjects included in analysis
    257
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.035
    Method
    		 Wald test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.63
    Confidence interval
         level
    		 99.7%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 1.21
    Statistical analysis title
    		 Sildenafil 80 mg versus Sildenafil 5 mg TID
    Statistical analysis description
    Hazard ratio estimated from the Proportional Hazards model, stratified by actual previous PAH treatment and etiology of PAH.
    Comparison groups
    Sildenafil 5 mg v Sildenafil 80 mg
    Number of subjects included in analysis
    257
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Wald test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.44
    Confidence interval
         level
    		 99.7%
         sides
    2-sided
         lower limit
    		 0.22
         upper limit
    		 0.89
    Statistical analysis title
    		 Sildenafil 80 mg versus Sildenafil 20 mg TID
    Statistical analysis description
    Hazard ratio estimated from the Proportional Hazards model, stratified by actual previous PAH treatment and etiology of PAH.
    Comparison groups
    Sildenafil 20 mg v Sildenafil 80 mg
    Number of subjects included in analysis
    256
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.195
    Method
    		 Wald test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.72
    Confidence interval
         level
    		 99.7%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 1.52

    Secondary: Change From Baseline in 6-Minute Walk Distance (6MWD) at Month 6

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    End point title
    		 Change From Baseline in 6-Minute Walk Distance (6MWD) at Month 6
    End point description
    6MWD was the distance that a subject could walk in 6 minutes. Subjects were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Analysis was performed using mixed model for repeated measures (MMRM), adjusted for baseline 6MWD and for randomisation stratification factors: PAH treatment at study entry and etiology of PAH. ITT population included all randomised subjects treated with study treatment. Here, “overall number of subjects analysed” signifies number of subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6
    End point values
    		 Sildenafil 5 mg Sildenafil 20 mg Sildenafil 80 mg
    Number of subjects analysed
    113
    118
    116
    Units: Meters
        least squares mean (confidence interval 95%)
    12.2 (-0.67 to 25.16)
    27.3 (14.52 to 39.99)
    31.2 (18.68 to 43.66)
    Statistical analysis title
    		 Sildenafil 20 mg versus Sildenafil 5 mg TID
    Comparison groups
    Sildenafil 5 mg v Sildenafil 20 mg
    Number of subjects included in analysis
    231
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0627
    Method
    		 MMRM
    Parameter type
    		 Least-squares means difference
    Point estimate
    15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 30.81
    Statistical analysis title
    		 Sildenafil 80 mg versus Sildenafil 20 mg TID
    Comparison groups
    Sildenafil 20 mg v Sildenafil 80 mg
    Number of subjects included in analysis
    234
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6254
    Method
    		 MMRM
    Parameter type
    		 Least-squares means difference
    Point estimate
    3.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.85
         upper limit
    		 19.68
    Statistical analysis title
    		 Sildenafil 80 mg versus Sildenafil 5 mg TID
    Comparison groups
    Sildenafil 5 mg v Sildenafil 80 mg
    Number of subjects included in analysis
    229
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0201
    Method
    		 MMRM
    Parameter type
    		 Least-squares means difference
    Point estimate
    18.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.99
         upper limit
    		 34.86

    Secondary: Change From Baseline in 6-Minute Walk Distance (6MWD) at Month 12

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    End point title
    		 Change From Baseline in 6-Minute Walk Distance (6MWD) at Month 12
    End point description
    6MWD was the distance that a subject could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Analysis was performed using mixed model for repeated measures (MMRM), adjusted for baseline 6MWD and for randomization stratification factors: PAH treatment at study entry and etiology of PAH. ITT population included all randomised subjects treated with study treatment. Here, “overall number of subjects analysed” signifies number of subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12
    End point values
    		 Sildenafil 5 mg Sildenafil 20 mg Sildenafil 80 mg
    Number of subjects analysed
    88
    89
    89
    Units: Meters
        least squares mean (confidence interval 95%)
    14.3 (-0.58 to 29.27)
    35.7 (20.91 to 50.48)
    34.8 (20.21 to 49.43)
    Statistical analysis title
    		 Sildenafil 20 mg versus Sildenafil 5 mg TID
    Comparison groups
    Sildenafil 5 mg v Sildenafil 20 mg
    Number of subjects included in analysis
    177
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0286
    Method
    		 MMRM
    Parameter type
    		 Least-squares means difference
    Point estimate
    21.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.25
         upper limit
    		 40.45
    Statistical analysis title
    		 Sildenafil 80 mg versus Sildenafil 5 mg TID
    Comparison groups
    Sildenafil 5 mg v Sildenafil 80 mg
    Number of subjects included in analysis
    177
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0364
    Method
    		 MMRM
    Parameter type
    		 Least-squares means difference
    Point estimate
    20.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.3
         upper limit
    		 39.65
    Statistical analysis title
    		 Sildenafil 80 mg versus Sildenafil 20 mg TID
    Comparison groups
    Sildenafil 20 mg v Sildenafil 80 mg
    Number of subjects included in analysis
    178
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9283
    Method
    		 MMRM
    Parameter type
    		 Least-squares means difference
    Point estimate
    -0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.94
         upper limit
    		 18.19

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to 28 days after last dose of study treatment (up to a maximum duration of 2108 days for sildenafil 5 mg; up to a maximum duration of 2012 days for sildenafil 20 mg; up to a maximum duration of 2101 days for sildenafil 80 mg)
    Adverse event reporting additional description
    An AE term may be reported as both a serious and non-serious AE, but are distinct events. An AE may be serious for 1 subject and non-serious for another subject, or a subject may have experienced both a serious and non-serious episode of the same event. Safety population comprised of all randomised subjects treated with study treatment.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Sildenafil 5 mg
    Reporting group description
    		 Subjects received a single tablet of sildenafil at a dose of 5 mg along with two tablets of placebo matching 20 mg and 80 mg sildenafil orally TID until discontinuation of study treatment or end of study. The maximum duration of study treatment was 2080 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.

    Reporting group title
    Sildenafil 20 mg
    Reporting group description
    		 Subjects received a single tablet of sildenafil at a dose of 20 mg along with two tablets of placebo matching 5 mg and 80 mg sildenafil orally TID until discontinuation of study treatment or end of study. The maximum duration of study treatment was 1984 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.

    Reporting group title
    Sildenafil 80 mg
    Reporting group description
    		 Subjects received a single tablet of sildenafil at a dose of 20 mg along with two tablets of placebo matching 5 mg and 80 mg sildenafil orally TID on day 1 for 2 weeks and then titrated up to 80 mg at week 2 along with two tablets of placebo matching 5 mg and 20 mg sildenafil orally TID until discontinuation of study treatment or end of study. The maximum duration of study treatment was 2073 days approximately. Subjects were followed up for at least 28 days after last dose of study treatment.

    Serious adverse events
    		 Sildenafil 5 mg Sildenafil 20 mg Sildenafil 80 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    66 / 129 (51.16%)
    49 / 128 (38.28%)
    51 / 128 (39.84%)
         number of deaths (all causes)
    34
    25
    19
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cervix carcinoma
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal carcinoma
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myelofibrosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleomorphic malignant fibrous histiocytoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural neoplasm
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic stenosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Varicose ulceration
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Drug therapy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hospitalisation
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung transplant
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Condition aggravated
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    Disease progression
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Exercise tolerance decreased
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    3 / 129 (2.33%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    Vascular stent stenosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst ruptured
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Alveolitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic respiratory failure
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    3 / 129 (2.33%)
    1 / 128 (0.78%)
    4 / 128 (3.13%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperventilation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary arterial hypertension
         subjects affected / exposed
    17 / 129 (13.18%)
    10 / 128 (7.81%)
    8 / 128 (6.25%)
         occurrences causally related to treatment / all
    0 / 23
    0 / 16
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    2 / 129 (1.55%)
    4 / 128 (3.13%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    3 / 129 (2.33%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic sclerosis pulmonary
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachypnoea
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vocal cord dysfunction
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Delusion
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Haemodynamic test
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Clavicle fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural intestinal perforation
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradyarrhythmia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 129 (0.78%)
    3 / 128 (2.34%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    9 / 129 (6.98%)
    8 / 128 (6.25%)
    3 / 128 (2.34%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 128 (1.56%)
    3 / 128 (2.34%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    11 / 129 (8.53%)
    4 / 128 (3.13%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular extrasystoles
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia paroxysmal
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypochromic anaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombosis mesenteric vessel
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Portal vein thrombosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Hypersensitivity vasculitis
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vasculitic rash
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    4 / 129 (3.10%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthropathy
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Connective tissue disorder
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oligoarthritis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoporotic fracture
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rheumatic disorder
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Scleroderma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    3 / 128 (2.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    3 / 128 (2.34%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Klebsiella bacteraemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leptospirosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis chronic
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    7 / 129 (5.43%)
    6 / 128 (4.69%)
    3 / 128 (2.34%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Septic shock
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal bacteraemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Sildenafil 5 mg Sildenafil 20 mg Sildenafil 80 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    108 / 129 (83.72%)
    107 / 128 (83.59%)
    111 / 128 (86.72%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-cell lymphoma stage IV
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Basal cell carcinoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Benign pancreatic neoplasm
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Bowen's disease
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Breast cancer
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Haemangioma of bone
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Haemangioma of liver
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    2
    Lipoma
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    2
    0
    1
    Malignant melanoma
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Melanocytic naevus
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Myelofibrosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Myeloproliferative neoplasm
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Polycythaemia vera
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Rectal neoplasm
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Skin papilloma
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Vascular disorders
    Aortic stenosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    3
    0
    2
    Cyanosis
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    2
    1
    1
    Deep vein thrombosis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Flushing
         subjects affected / exposed
    6 / 129 (4.65%)
    3 / 128 (2.34%)
    4 / 128 (3.13%)
         occurrences all number
    6
    5
    4
    Haematoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    2
    Haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Hot flush
         subjects affected / exposed
    0 / 129 (0.00%)
    3 / 128 (2.34%)
    2 / 128 (1.56%)
         occurrences all number
    0
    3
    3
    Hyperaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Hypertension
         subjects affected / exposed
    2 / 129 (1.55%)
    6 / 128 (4.69%)
    5 / 128 (3.91%)
         occurrences all number
    2
    9
    5
    Hypertensive crisis
         subjects affected / exposed
    3 / 129 (2.33%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    3
    0
    0
    Hypotension
         subjects affected / exposed
    9 / 129 (6.98%)
    6 / 128 (4.69%)
    7 / 128 (5.47%)
         occurrences all number
    11
    6
    15
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Labile blood pressure
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Lymphoedema
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Neovascularisation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Pelvic venous thrombosis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Peripheral venous disease
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Phlebitis
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    2
    1
    0
    Raynaud's phenomenon
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Thrombophlebitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Varicose vein
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Vasodilatation
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Surgical and medical procedures
    Cancer surgery
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Cardiac ablation
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Cataract operation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    3 / 128 (2.34%)
         occurrences all number
    0
    2
    4
    Dental operation
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Haematoma evacuation
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Myomectomy
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Tooth extraction
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    2
    1
    Tooth repair
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Vascular operation
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 129 (2.33%)
    7 / 128 (5.47%)
    2 / 128 (1.56%)
         occurrences all number
    3
    14
    3
    Catheter site erythema
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Chest discomfort
         subjects affected / exposed
    3 / 129 (2.33%)
    3 / 128 (2.34%)
    0 / 128 (0.00%)
         occurrences all number
    11
    6
    0
    Chest pain
         subjects affected / exposed
    7 / 129 (5.43%)
    15 / 128 (11.72%)
    13 / 128 (10.16%)
         occurrences all number
    9
    30
    72
    Chills
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    5 / 128 (3.91%)
         occurrences all number
    2
    1
    5
    Crying
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Cyst
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    3
    Disease progression
         subjects affected / exposed
    3 / 129 (2.33%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    3
    0
    0
    Face oedema
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Facial pain
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Fatigue
         subjects affected / exposed
    11 / 129 (8.53%)
    10 / 128 (7.81%)
    9 / 128 (7.03%)
         occurrences all number
    19
    17
    18
    Feeling cold
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    4
    1
    0
    Feeling hot
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    16
    2
    0
    Gait disturbance
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    General physical health deterioration
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Generalised oedema
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Ill-defined disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Inflammation
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Infusion site pain
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Injection site hypersensitivity
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Malaise
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    0
    3
    1
    Mucosal dryness
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Oedema
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 128 (1.56%)
    3 / 128 (2.34%)
         occurrences all number
    5
    2
    4
    Oedema peripheral
         subjects affected / exposed
    14 / 129 (10.85%)
    17 / 128 (13.28%)
    8 / 128 (6.25%)
         occurrences all number
    18
    25
    9
    Pain
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    3 / 128 (2.34%)
         occurrences all number
    3
    3
    3
    Peripheral swelling
         subjects affected / exposed
    7 / 129 (5.43%)
    6 / 128 (4.69%)
    5 / 128 (3.91%)
         occurrences all number
    9
    6
    7
    Pyrexia
         subjects affected / exposed
    3 / 129 (2.33%)
    9 / 128 (7.03%)
    9 / 128 (7.03%)
         occurrences all number
    3
    11
    15
    Swelling
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Swelling face
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Ulcer
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Vessel puncture site bruise
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Vessel puncture site haematoma
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Immune system disorders
    Allergy to arthropod bite
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Drug hypersensitivity
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Food allergy
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Hypersensitivity
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    3
    2
    1
    Multiple allergies
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Secondary immunodeficiency
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Reproductive system and breast disorders
    Amenorrhoea
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Breast cyst
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    2
    Breast inflammation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Breast mass
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Breast pain
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Dysfunctional uterine bleeding
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Dysmenorrhoea
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    6
    1
    Endometriosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Gynaecomastia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Menorrhagia
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    2
    0
    1
    Menstrual disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Ovarian cyst
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Priapism
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Uterine polyp
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    3
    1
    Vulvovaginal pruritus
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Alveolitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Asthma
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    0
    1
    3
    Bronchial hyperreactivity
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Bronchitis chronic
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    0
    1
    2
    Bronchopneumopathy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Catarrh
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    0
    1
    4
    Chronic respiratory failure
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Cough
         subjects affected / exposed
    14 / 129 (10.85%)
    11 / 128 (8.59%)
    12 / 128 (9.38%)
         occurrences all number
    24
    14
    25
    Dysphonia
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    3
    1
    0
    Dyspnoea
         subjects affected / exposed
    12 / 129 (9.30%)
    16 / 128 (12.50%)
    11 / 128 (8.59%)
         occurrences all number
    15
    35
    16
    Dyspnoea exertional
         subjects affected / exposed
    1 / 129 (0.78%)
    3 / 128 (2.34%)
    0 / 128 (0.00%)
         occurrences all number
    1
    4
    0
    Emphysema
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Epistaxis
         subjects affected / exposed
    11 / 129 (8.53%)
    13 / 128 (10.16%)
    13 / 128 (10.16%)
         occurrences all number
    12
    21
    22
    Haemoptysis
         subjects affected / exposed
    1 / 129 (0.78%)
    3 / 128 (2.34%)
    1 / 128 (0.78%)
         occurrences all number
    2
    3
    1
    Hiccups
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperventilation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Hypoxia
         subjects affected / exposed
    0 / 129 (0.00%)
    3 / 128 (2.34%)
    0 / 128 (0.00%)
         occurrences all number
    0
    4
    0
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Increased upper airway secretion
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Interstitial lung disease
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Lung disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Lung infiltration
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Nasal congestion
         subjects affected / exposed
    8 / 129 (6.20%)
    4 / 128 (3.13%)
    5 / 128 (3.91%)
         occurrences all number
    10
    6
    5
    Nasal dryness
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    2 / 129 (1.55%)
    6 / 128 (4.69%)
    2 / 128 (1.56%)
         occurrences all number
    2
    11
    3
    Paranasal sinus discomfort
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Pharyngeal swelling
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Pleural effusion
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Pleurisy
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Pleuritic pain
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Productive cough
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    1
    2
    1
    Prolonged expiration
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Pulmonary arterial hypertension
         subjects affected / exposed
    10 / 129 (7.75%)
    7 / 128 (5.47%)
    4 / 128 (3.13%)
         occurrences all number
    15
    8
    7
    Pulmonary embolism
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Pulmonary fibrosis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Pulmonary vascular disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Rales
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Respiratory disorder
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    4
    0
    0
    Respiratory failure
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    2
    1
    1
    Rhinitis allergic
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    1
    2
    0
    Rhinorrhoea
         subjects affected / exposed
    2 / 129 (1.55%)
    4 / 128 (3.13%)
    3 / 128 (2.34%)
         occurrences all number
    2
    5
    3
    Rhonchi
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Sinonasal obstruction
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Sinus congestion
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Sneezing
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Throat irritation
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    0
    1
    3
    Vasomotor rhinitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Vocal cord polyp
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Wheezing
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    3
    2
    1
    Apathy
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Confusional state
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Depressed mood
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Depression
         subjects affected / exposed
    1 / 129 (0.78%)
    3 / 128 (2.34%)
    1 / 128 (0.78%)
         occurrences all number
    1
    3
    1
    Emotional disorder
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Initial insomnia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Insomnia
         subjects affected / exposed
    4 / 129 (3.10%)
    5 / 128 (3.91%)
    2 / 128 (1.56%)
         occurrences all number
    27
    6
    2
    Mental disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Mood altered
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Mood swings
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Nervousness
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Sleep disorder
         subjects affected / exposed
    2 / 129 (1.55%)
    3 / 128 (2.34%)
    1 / 128 (0.78%)
         occurrences all number
    5
    3
    1
    Product issues
    Device breakage
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Device fastener issue
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatobiliary disorders
    Biliary dilatation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Biliary dyskinesia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Cardiac cirrhosis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Cholecystitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Cholecystocholangitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Cholelithiasis
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    4
    3
    1
    Congestive hepatopathy
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatic steatosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Hepatitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatomegaly
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    2
    Hepatosplenomegaly
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    3 / 129 (2.33%)
    4 / 128 (3.13%)
    0 / 128 (0.00%)
         occurrences all number
    3
    4
    0
    Liver disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Ocular icterus
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    1
    2
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Blood albumin abnormal
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    1
    1
    1
    Blood bilirubin increased
         subjects affected / exposed
    3 / 129 (2.33%)
    3 / 128 (2.34%)
    3 / 128 (2.34%)
         occurrences all number
    7
    3
    3
    Blood cholesterol increased
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    1
    1
    1
    Blood glucose decreased
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Blood iron decreased
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Blood potassium abnormal
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Blood pressure decreased
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    0
    4
    2
    Blood pressure diastolic decreased
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    2
    1
    1
    Blood pressure increased
         subjects affected / exposed
    3 / 129 (2.33%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    12
    1
    2
    Blood pressure measurement
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Blood urea increased
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    1
    1
    1
    Blood uric acid increased
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    2 / 128 (1.56%)
         occurrences all number
    0
    2
    2
    Body temperature increased
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    0
    9
    1
    Breath sounds abnormal
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Colonoscopy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Endoscopy
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Fibrin D dimer increased
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Haemodynamic test
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Heart rate
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Heart rate decreased
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Heart rate increased
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Heart sounds abnormal
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Liver function test abnormal
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Oxygen saturation decreased
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Protein total abnormal
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Staphylococcus test positive
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Transaminases increased
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Troponin increased
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Ultrasound scan
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Venous pressure jugular increased
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Vitamin D decreased
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Walking distance test abnormal
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    3
    0
    0
    Weight decreased
         subjects affected / exposed
    4 / 129 (3.10%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    7
    1
    2
    Weight increased
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    2
    1
    1
    White blood cell count increased
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    0
    1
    2
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    0
    3
    1
    Arthropod sting
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Back injury
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Burn oral cavity
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Chest injury
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Contusion
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    1
    2
    1
    Endotracheal intubation complication
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Epicondylitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Exposure via breast milk
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Facial bones fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Fall
         subjects affected / exposed
    4 / 129 (3.10%)
    2 / 128 (1.56%)
    3 / 128 (2.34%)
         occurrences all number
    4
    2
    5
    Head injury
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    0
    2
    1
    Humerus fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Ligament sprain
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Limb injury
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Lower limb fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Muscle injury
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Muscle rupture
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Muscle strain
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    1
    1
    2
    Nasal injury
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Oral contusion
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Procedural pain
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Rib fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    0
    2
    1
    Road traffic accident
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Scar
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Skin abrasion
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Skin laceration
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Soft tissue injury
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Thermal burn
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Tooth fracture
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    2
    1
    0
    Upper limb fracture
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    2
    2
    1
    Thyroid malformation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Angina pectoris
         subjects affected / exposed
    0 / 129 (0.00%)
    4 / 128 (3.13%)
    2 / 128 (1.56%)
         occurrences all number
    0
    8
    3
    Arrhythmia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    3
    Atrial fibrillation
         subjects affected / exposed
    2 / 129 (1.55%)
    3 / 128 (2.34%)
    2 / 128 (1.56%)
         occurrences all number
    2
    4
    2
    Atrial flutter
         subjects affected / exposed
    3 / 129 (2.33%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    4
    1
    1
    Atrial thrombosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Atrioventricular block first degree
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Bradycardia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Cardiac failure
         subjects affected / exposed
    3 / 129 (2.33%)
    0 / 128 (0.00%)
    3 / 128 (2.34%)
         occurrences all number
    3
    0
    4
    Cardiac failure acute
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Cardiac failure congestive
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    1
    2
    1
    Cardiac ventricular thrombosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Extrasystoles
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Palpitations
         subjects affected / exposed
    5 / 129 (3.88%)
    5 / 128 (3.91%)
    6 / 128 (4.69%)
         occurrences all number
    6
    6
    19
    Pericardial effusion
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    3
    1
    Right ventricular dysfunction
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Right ventricular failure
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    3
    2
    0
    Supraventricular extrasystoles
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    3
    0
    0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Tachycardia
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 128 (1.56%)
    5 / 128 (3.91%)
         occurrences all number
    3
    7
    5
    Tricuspid valve incompetence
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    2
    0
    2
    Ventricular tachycardia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Amnesia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Anosmia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Aphasia
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Balance disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Burning sensation
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Cerebral atrophy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Cervical radiculopathy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Cognitive disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Diabetic neuropathy
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Dizziness
         subjects affected / exposed
    12 / 129 (9.30%)
    15 / 128 (11.72%)
    18 / 128 (14.06%)
         occurrences all number
    17
    21
    30
    Dizziness exertional
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    4
    0
    Encephalopathy
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Epilepsy
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Head discomfort
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Headache
         subjects affected / exposed
    26 / 129 (20.16%)
    45 / 128 (35.16%)
    33 / 128 (25.78%)
         occurrences all number
    105
    106
    95
    Hypoaesthesia
         subjects affected / exposed
    2 / 129 (1.55%)
    3 / 128 (2.34%)
    2 / 128 (1.56%)
         occurrences all number
    3
    5
    2
    Hypotonia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Intercostal neuralgia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Lethargy
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Loss of consciousness
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Migraine
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    10
    0
    Neuralgia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Neuritis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    2 / 129 (1.55%)
    3 / 128 (2.34%)
    2 / 128 (1.56%)
         occurrences all number
    3
    4
    3
    Postictal paralysis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Presyncope
         subjects affected / exposed
    1 / 129 (0.78%)
    4 / 128 (3.13%)
    1 / 128 (0.78%)
         occurrences all number
    1
    6
    1
    Radiculopathy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Sciatica
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Sensory loss
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Sinus headache
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    4
    Somnolence
         subjects affected / exposed
    3 / 129 (2.33%)
    5 / 128 (3.91%)
    0 / 128 (0.00%)
         occurrences all number
    4
    7
    0
    Syncope
         subjects affected / exposed
    4 / 129 (3.10%)
    4 / 128 (3.13%)
    4 / 128 (3.13%)
         occurrences all number
    6
    10
    5
    Tension headache
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Tremor
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    3 / 128 (2.34%)
         occurrences all number
    0
    0
    4
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Trigeminal neuritis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Vascular encephalopathy
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 129 (3.88%)
    3 / 128 (2.34%)
    11 / 128 (8.59%)
         occurrences all number
    6
    3
    15
    Bicytopenia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Blood loss anaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Cytopenia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Heparin-induced thrombocytopenia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Hypothrombinaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Increased tendency to bruise
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Leukopenia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Lymphadenopathy
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    0
    2
    1
    Lymphocytosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Macrocytosis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Pancytopenia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Polycythaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Splenomegaly
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Thrombocytopenia
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 128 (1.56%)
    3 / 128 (2.34%)
         occurrences all number
    2
    2
    3
    Lymphadenitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Iron deficiency anaemia
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    3 / 128 (2.34%)
         occurrences all number
    2
    0
    3
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Ear congestion
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Ear haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    5
    Ear pain
         subjects affected / exposed
    1 / 129 (0.78%)
    3 / 128 (2.34%)
    1 / 128 (0.78%)
         occurrences all number
    1
    3
    1
    Hypoacusis
         subjects affected / exposed
    3 / 129 (2.33%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    4
    2
    0
    Mixed deafness
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Tinnitus
         subjects affected / exposed
    1 / 129 (0.78%)
    4 / 128 (3.13%)
    1 / 128 (0.78%)
         occurrences all number
    1
    6
    1
    Vertigo
         subjects affected / exposed
    2 / 129 (1.55%)
    4 / 128 (3.13%)
    2 / 128 (1.56%)
         occurrences all number
    2
    4
    2
    Eye disorders
    Asthenopia
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Astigmatism
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Blepharitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Cataract
         subjects affected / exposed
    4 / 129 (3.10%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    4
    0
    2
    Chalazion
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Chromatopsia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    4
    1
    Cornea verticillata
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Corneal oedema
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Corneal opacity
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Dacryostenosis acquired
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Dark circles under eyes
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Diplopia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Dry eye
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    1
    1
    1
    Dyschromatopsia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Eye disorder
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    2
    1
    0
    Eye haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Eye inflammation
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Eye irritation
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    2
    0
    1
    Eye pain
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    3 / 128 (2.34%)
         occurrences all number
    0
    0
    6
    Eye pruritus
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Eye swelling
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Foreign body sensation in eyes
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    5
    0
    Glaucoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Hypermetropia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Keratitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Lacrimation increased
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Macular degeneration
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Maculopathy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    2
    Periorbital pain
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Periorbital swelling
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    0
    3
    1
    Photophobia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Photopsia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Pterygium
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Retinal vascular disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    0
    2
    1
    Swelling of eyelid
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Vision blurred
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 128 (1.56%)
    2 / 128 (1.56%)
         occurrences all number
    3
    3
    2
    Visual impairment
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    4 / 128 (3.13%)
         occurrences all number
    1
    2
    5
    Visual snow syndrome
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Xerophthalmia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    2
    1
    0
    Abdominal distension
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    2 / 128 (1.56%)
         occurrences all number
    2
    2
    2
    Abdominal pain
         subjects affected / exposed
    5 / 129 (3.88%)
    5 / 128 (3.91%)
    4 / 128 (3.13%)
         occurrences all number
    8
    12
    6
    Abdominal pain lower
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    6 / 129 (4.65%)
    7 / 128 (5.47%)
    11 / 128 (8.59%)
         occurrences all number
    12
    29
    15
    Abdominal symptom
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Angular cheilitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Ascites
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    3
    2
    1
    Barrett's oesophagus
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Chronic gastritis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    2
    0
    1
    Colitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Constipation
         subjects affected / exposed
    5 / 129 (3.88%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    5
    1
    1
    Dental necrosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    13 / 129 (10.08%)
    17 / 128 (13.28%)
    20 / 128 (15.63%)
         occurrences all number
    27
    45
    28
    Diverticulum intestinal
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Dry mouth
         subjects affected / exposed
    0 / 129 (0.00%)
    3 / 128 (2.34%)
    3 / 128 (2.34%)
         occurrences all number
    0
    4
    3
    Duodenal bulb deformity
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Duodenal ulcer
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Duodenal vascular ectasia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Duodenogastric reflux
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Dyspepsia
         subjects affected / exposed
    6 / 129 (4.65%)
    10 / 128 (7.81%)
    10 / 128 (7.81%)
         occurrences all number
    8
    12
    24
    Dysphagia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Enteritis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Enterocolitis
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    3
    0
    1
    Epigastric discomfort
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    3
    0
    1
    Eructation
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Faeces discoloured
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Flatulence
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    4
    0
    Food poisoning
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    3 / 128 (2.34%)
         occurrences all number
    1
    2
    4
    Frequent bowel movements
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Gastric disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    3 / 128 (2.34%)
    1 / 128 (0.78%)
         occurrences all number
    0
    13
    1
    Gastric polyps
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Gastritis
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 128 (1.56%)
    3 / 128 (2.34%)
         occurrences all number
    3
    2
    3
    Gastritis erosive
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    4 / 128 (3.13%)
         occurrences all number
    1
    2
    5
    Gingival bleeding
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    2
    0
    1
    Gingival hypertrophy
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Gingival pain
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Haematochezia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    2
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    2
    Hiatus hernia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    2
    0
    1
    Hypoaesthesia oral
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    0
    0
    3
    Intestinal haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Intestinal polyp
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Irritable bowel syndrome
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Large intestine polyp
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    1
    0
    2
    Mouth haemorrhage
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    2
    Mouth ulceration
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Nausea
         subjects affected / exposed
    16 / 129 (12.40%)
    12 / 128 (9.38%)
    8 / 128 (6.25%)
         occurrences all number
    17
    20
    12
    Odynophagia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Oesophageal disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Pancreatitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    0
    1
    2
    Peptic ulcer
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Stomatitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Tongue erythema
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Tongue ulceration
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Toothache
         subjects affected / exposed
    5 / 129 (3.88%)
    5 / 128 (3.91%)
    3 / 128 (2.34%)
         occurrences all number
    5
    5
    3
    Umbilical hernia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Varices oesophageal
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Vomiting
         subjects affected / exposed
    7 / 129 (5.43%)
    10 / 128 (7.81%)
    7 / 128 (5.47%)
         occurrences all number
    11
    14
    8
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 129 (0.00%)
    3 / 128 (2.34%)
    0 / 128 (0.00%)
         occurrences all number
    0
    3
    0
    Chronic spontaneous urticaria
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Dermatitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Dermatitis allergic
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    3 / 128 (2.34%)
         occurrences all number
    0
    0
    3
    Dermatitis atopic
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Diabetic foot
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Dry skin
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Eczema nummular
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Erythema
         subjects affected / exposed
    2 / 129 (1.55%)
    4 / 128 (3.13%)
    4 / 128 (3.13%)
         occurrences all number
    31
    7
    5
    Hyperhidrosis
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    3
    2
    0
    Hypersensitivity vasculitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Photosensitivity reaction
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Pruritus
         subjects affected / exposed
    4 / 129 (3.10%)
    3 / 128 (2.34%)
    3 / 128 (2.34%)
         occurrences all number
    5
    3
    3
    Rash
         subjects affected / exposed
    3 / 129 (2.33%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    7
    1
    3
    Rash erythematous
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Rash macular
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    1
    1
    1
    Rash papular
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Skin burning sensation
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Skin disorder
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Skin fissures
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Skin irritation
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Skin lesion
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Skin ulcer
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    2
    2
    2
    Telangiectasia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Vitiligo
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Yellow skin
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Azotaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Chronic kidney disease
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Dysuria
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Haematuria
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    3
    0
    Proteinuria
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Pyelocaliectasis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Renal cyst
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    3 / 128 (2.34%)
         occurrences all number
    3
    1
    3
    Renal failure
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    1
    2
    3
    Renal impairment
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    1
    1
    2
    Urinary retention
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Endocrine disorders
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Cushing's syndrome
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Hyperthyroidism
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Hypothyroidism
         subjects affected / exposed
    2 / 129 (1.55%)
    4 / 128 (3.13%)
    2 / 128 (1.56%)
         occurrences all number
    2
    4
    2
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Primary hypothyroidism
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Thyroid mass
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    14 / 129 (10.85%)
    13 / 128 (10.16%)
    15 / 128 (11.72%)
         occurrences all number
    17
    19
    24
    Arthritis
         subjects affected / exposed
    3 / 129 (2.33%)
    3 / 128 (2.34%)
    0 / 128 (0.00%)
         occurrences all number
    3
    4
    0
    Back pain
         subjects affected / exposed
    16 / 129 (12.40%)
    10 / 128 (7.81%)
    14 / 128 (10.94%)
         occurrences all number
    20
    24
    23
    Bone pain
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    0
    6
    1
    Bursitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Gouty arthritis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Joint swelling
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    2
    1
    2
    Limb mass
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Metatarsalgia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Muscle contracture
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Muscle spasms
         subjects affected / exposed
    4 / 129 (3.10%)
    3 / 128 (2.34%)
    3 / 128 (2.34%)
         occurrences all number
    5
    5
    5
    Muscular weakness
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    1
    2
    0
    Musculoskeletal discomfort
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal disorder
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    4 / 129 (3.10%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    4
    0
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    3
    1
    Myalgia
         subjects affected / exposed
    4 / 129 (3.10%)
    10 / 128 (7.81%)
    12 / 128 (9.38%)
         occurrences all number
    5
    16
    17
    Neck pain
         subjects affected / exposed
    0 / 129 (0.00%)
    3 / 128 (2.34%)
    4 / 128 (3.13%)
         occurrences all number
    0
    4
    4
    Osteitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Osteoarthritis
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    3 / 128 (2.34%)
         occurrences all number
    1
    3
    3
    Osteochondrosis
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    4 / 128 (3.13%)
         occurrences all number
    2
    1
    4
    Osteopenia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Osteoporosis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Osteoporotic fracture
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Pain in extremity
         subjects affected / exposed
    6 / 129 (4.65%)
    14 / 128 (10.94%)
    6 / 128 (4.69%)
         occurrences all number
    7
    17
    13
    Pain in jaw
         subjects affected / exposed
    3 / 129 (2.33%)
    3 / 128 (2.34%)
    1 / 128 (0.78%)
         occurrences all number
    3
    3
    2
    Pathological fracture
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Plantar fasciitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Polymyalgia rheumatica
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Sclerodactylia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Scleroderma
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Sjogren's syndrome
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Spinal disorder
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    2
    0
    1
    Spinal pain
         subjects affected / exposed
    1 / 129 (0.78%)
    3 / 128 (2.34%)
    0 / 128 (0.00%)
         occurrences all number
    2
    4
    0
    Systemic lupus erythematosus
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Systemic scleroderma
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    3
    0
    Temporomandibular joint syndrome
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Tendonitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    3
    0
    Trigger finger
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Undifferentiated connective tissue disease
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Acute sinusitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    3 / 128 (2.34%)
         occurrences all number
    1
    0
    3
    Bacterial disease carrier
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Bacterial infection
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Bacterial rhinitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Bronchitis
         subjects affected / exposed
    11 / 129 (8.53%)
    11 / 128 (8.59%)
    8 / 128 (6.25%)
         occurrences all number
    16
    11
    8
    Bronchitis viral
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    COVID-19
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Cellulitis
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    3
    2
    1
    Chronic sinusitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Chronic tonsillitis 0 0
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Conjunctivitis
         subjects affected / exposed
    5 / 129 (3.88%)
    1 / 128 (0.78%)
    6 / 128 (4.69%)
         occurrences all number
    5
    1
    7
    Cystitis
         subjects affected / exposed
    3 / 129 (2.33%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    4
    3
    0
    Device related infection
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Device related sepsis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Diverticulitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Ear infection
         subjects affected / exposed
    4 / 129 (3.10%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    5
    1
    0
    Enteritis infectious
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Erysipelas
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Eye infection
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Gastric infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Gastroenteritis
         subjects affected / exposed
    4 / 129 (3.10%)
    1 / 128 (0.78%)
    3 / 128 (2.34%)
         occurrences all number
    5
    1
    3
    Gastroenteritis viral
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    4
    0
    Gastrointestinal candidiasis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Gastrointestinal infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal viral infection
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Genital infection female
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Gingivitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Groin abscess
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Helicobacter gastritis
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    2
    0
    1
    Helicobacter infection
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatitis B
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Herpes simplex
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    1
    8
    2
    Herpes virus infection
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Herpes zoster
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Hordeolum
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Incision site abscess
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Influenza
         subjects affected / exposed
    6 / 129 (4.65%)
    8 / 128 (6.25%)
    11 / 128 (8.59%)
         occurrences all number
    7
    12
    16
    Joint abscess
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Laryngitis
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    2 / 128 (1.56%)
         occurrences all number
    0
    2
    2
    Localised infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    0
    1
    2
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    19 / 129 (14.73%)
    16 / 128 (12.50%)
    19 / 128 (14.84%)
         occurrences all number
    44
    34
    40
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Onychomycosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Oral candidiasis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    2 / 128 (1.56%)
         occurrences all number
    1
    0
    4
    Oral fungal infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Oral herpes
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    2
    0
    1
    Otitis media
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Otitis media chronic
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Paronychia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Periodontitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    3 / 128 (2.34%)
         occurrences all number
    1
    0
    4
    Pharyngitis bacterial
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    5 / 129 (3.88%)
    3 / 128 (2.34%)
    5 / 128 (3.91%)
         occurrences all number
    5
    3
    6
    Pulpitis dental
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    1
    1
    1
    Pyelonephritis chronic
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    5 / 129 (3.88%)
    4 / 128 (3.13%)
    6 / 128 (4.69%)
         occurrences all number
    9
    4
    6
    Respiratory tract infection viral
         subjects affected / exposed
    4 / 129 (3.10%)
    5 / 128 (3.91%)
    8 / 128 (6.25%)
         occurrences all number
    4
    6
    13
    Rhinitis
         subjects affected / exposed
    5 / 129 (3.88%)
    5 / 128 (3.91%)
    1 / 128 (0.78%)
         occurrences all number
    5
    8
    1
    Salpingo-oophoritis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Sinusitis
         subjects affected / exposed
    3 / 129 (2.33%)
    3 / 128 (2.34%)
    10 / 128 (7.81%)
         occurrences all number
    7
    6
    16
    Skin infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    1
    Tinea pedis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Tongue fungal infection
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Tonsillitis
         subjects affected / exposed
    1 / 129 (0.78%)
    3 / 128 (2.34%)
    1 / 128 (0.78%)
         occurrences all number
    2
    3
    1
    Tonsillitis bacterial
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Tooth abscess
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Tracheitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    4
    0
    1
    Tracheobronchitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    16 / 129 (12.40%)
    8 / 128 (6.25%)
    13 / 128 (10.16%)
         occurrences all number
    41
    9
    27
    Urinary tract infection
         subjects affected / exposed
    4 / 129 (3.10%)
    1 / 128 (0.78%)
    5 / 128 (3.91%)
         occurrences all number
    4
    2
    5
    Vaginal infection
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Varicella
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Viral infection
         subjects affected / exposed
    4 / 129 (3.10%)
    5 / 128 (3.91%)
    3 / 128 (2.34%)
         occurrences all number
    5
    5
    3
    Viral rhinitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    1
    2
    0
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Calcium deficiency
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Decreased appetite
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 128 (1.56%)
    2 / 128 (1.56%)
         occurrences all number
    6
    2
    3
    Dehydration
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Diabetes mellitus
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Fluid overload
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    2
    0
    1
    Fluid retention
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    2 / 128 (1.56%)
         occurrences all number
    2
    1
    2
    Glucose tolerance impaired
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    1
    0
    0
    Gout
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 128 (1.56%)
    1 / 128 (0.78%)
         occurrences all number
    2
    2
    1
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    1
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    2 / 129 (1.55%)
    4 / 128 (3.13%)
    0 / 128 (0.00%)
         occurrences all number
    2
    4
    0
    Hyperlipidaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Hypernatraemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Hyperuricaemia
         subjects affected / exposed
    3 / 129 (2.33%)
    1 / 128 (0.78%)
    3 / 128 (2.34%)
         occurrences all number
    3
    1
    3
    Hypocalcaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0
    Hypokalaemia
         subjects affected / exposed
    10 / 129 (7.75%)
    6 / 128 (4.69%)
    5 / 128 (3.91%)
         occurrences all number
    12
    9
    7
    Hypomagnesaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 128 (0.78%)
         occurrences all number
    0
    1
    2
    Hyponatraemia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    1
    0
    1
    Impaired fasting glucose
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Insulin resistance
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Iron deficiency
         subjects affected / exposed
    0 / 129 (0.00%)
    3 / 128 (2.34%)
    2 / 128 (1.56%)
         occurrences all number
    0
    3
    2
    Mineral metabolism disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 128 (0.78%)
         occurrences all number
    0
    0
    1
    Obesity
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 128 (0.00%)
         occurrences all number
    0
    2
    0
    Steroid diabetes
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 128 (0.00%)
         occurrences all number
    2
    0
    0
    Vitamin D deficiency
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 128 (0.00%)
         occurrences all number
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Nov 2014
    Permit short term phosphodiesterase type 5 inhibitor (PDE5I) use prior to enrollment. Allow temporary discontinuation (up to 14 days) of study treatment to permit temporary treatment with prohibited medications for comorbidities. Addition of riociguat as a prohibited medication.
    28 Aug 2020
    To increase, in a blinded manner, the dose for subjects receiving 5 mg (TID) to 20 mg (TID), the approved dose in these 5 countries.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Study stopped by DMC after first IA (primary objective met). OS and clinical worsening (CW) sig level adjusted for IA (99.7% CIs used instead of 95% CIs). OS 80mg v 5mg primary, CW 80mg v 5mg key secondary. Other comparisons / endpoints are nominal.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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