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    Clinical Trial Results:
    A Phase 3, Placebo-Controlled, Randomised, Observer-Blinded Study to Evaluate the Efficacy, Safety, And Tolerability of a Clostridium Difficile Vaccine in Adults 50 Years of Age and Older

    Summary
    EudraCT number
    		 2016-003866-14
    Trial protocol
    		 SK   BG   SE   HU   BE   CZ   GB   DE   FI   PT   ES   PL   FR  
    Global end of trial date
    21 Dec 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Dec 2022
    First version publication date
    16 Dec 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    B5091007
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03090191
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.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
    11 Feb 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Dec 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that Pfizer’s C difficile vaccine is effective in reducing the incidence of a first primary episode of CDI and to evaluate the safety profile of Pfizer’s C difficile vaccine as measured by the percentage of subjects reporting local reactions and systemic events, Adverse Events (AEs), and Serious Adverse Events (SAEs).
    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 Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Mar 2017
    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
    Argentina: 118
    Country: Number of subjects enrolled
    Australia: 258
    Country: Number of subjects enrolled
    Belgium: 19
    Country: Number of subjects enrolled
    Bulgaria: 868
    Country: Number of subjects enrolled
    Canada: 449
    Country: Number of subjects enrolled
    Chile: 37
    Country: Number of subjects enrolled
    Colombia: 456
    Country: Number of subjects enrolled
    Czechia: 141
    Country: Number of subjects enrolled
    Germany: 301
    Country: Number of subjects enrolled
    Spain: 204
    Country: Number of subjects enrolled
    Finland: 119
    Country: Number of subjects enrolled
    France: 60
    Country: Number of subjects enrolled
    United Kingdom: 224
    Country: Number of subjects enrolled
    Hungary: 600
    Country: Number of subjects enrolled
    Japan: 1062
    Country: Number of subjects enrolled
    Korea, Republic of: 175
    Country: Number of subjects enrolled
    Peru: 61
    Country: Number of subjects enrolled
    Poland: 671
    Country: Number of subjects enrolled
    Portugal: 75
    Country: Number of subjects enrolled
    Slovakia: 369
    Country: Number of subjects enrolled
    Sweden: 185
    Country: Number of subjects enrolled
    Taiwan: 89
    Country: Number of subjects enrolled
    United States: 10899
    Worldwide total number of subjects
    17440
    EEA total number of subjects
    3612
    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)
    5925
    From 65 to 84 years
    11184
    85 years and over
    331

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 18095 subjects signed the informed consent form (ICF). Among that 560 subjects did not meet all eligibility criteria, were not randomised and vaccinated. Overall, 17535 subjects were randomised. Among those,17440 subjects received at least 1 dose of the investigational product.

    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
    		 Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Clostridium difficile Vaccine
    Arm description
    		 Subjects received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Clostridium difficile
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 200 microgram total toxoid per dose intramuscularly.

    Arm title
    		 Placebo
    Arm description
    		 Subjects received placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly at Months 0, 1 and 6.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Normal saline solution
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received Normal saline solution of 0.9 percent [%] sodium chloride intramuscularly.

    Number of subjects in period 1
    		Clostridium difficile Vaccine Placebo
    Started
    8722
    8718
    Vaccinated at Month 0 (Dose 1)
    8722
    8718
    Vaccinated at Month 1 (Dose 2)
    8311
    8331
    Vaccinated at Month 6 (Dose 3)
    7894
    7967
    Completed
    5532
    5575
    Not completed
    3190
    3143
         Adverse event, serious fatal
    368
    358
         Consent withdrawn by subject
    2160
    2133
         Physician decision
    77
    66
         Adverse event, non-fatal
    87
    72
         Site terminated
    7
    8
         Unspecified
    66
    60
         Lost to follow-up
    382
    394
         Protocol deviation
    43
    52

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Clostridium difficile Vaccine
    Reporting group description
    		 Subjects received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly at Months 0, 1 and 6.

    Reporting group values
    		 Clostridium difficile Vaccine Placebo Total
    Number of subjects
    		 8722 8718 17440
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 2962 2963 5925
        From 65-84 years
    		 5597 5587 11184
        85 years and over
    		 163 168 331
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 68.0 ( 7.5 ) 68.1 ( 7.5 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 4472 4501 8973
        Male
    		 4250 4217 8467
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 53 54 107
        Asian
    		 754 725 1479
        Native Hawaiian or Other Pacific Islander
    		 20 14 34
        Black or African American
    		 663 666 1329
        White
    		 6891 6922 13813
        More than one race
    		 327 322 649
        Unknown or Not Reported
    		 14 15 29
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 1119 1143 2262
        Not Hispanic or Latino
    		 7546 7515 15061
        Unknown or Not Reported
    		 57 60 117

    End points

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    End points reporting groups
    Reporting group title
    Clostridium difficile Vaccine
    Reporting group description
    		 Subjects received Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly at Months 0, 1 and 6.

    Primary: Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 3

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    End point title
    		 Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 3
    End point description
    CDI definition 1 for a primary episode of CDI(no previous CDI onset in prior 8 weeks)defined as either a) presence of diarrhea(passage of 3 or more unformed stools[Bristol stool chart types 5-7]) in 24 or fewer consecutive hours,stool sample positive for toxin B gene(by polymerase chain reaction[PCR)] and positive for toxin A and/or toxin B,as measured in central laboratory;or b)Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically;and corresponding stool sample positive for toxin B gene(via PCR)as measured in central laboratory. End of surveillance period was defined as accumulation of at least 40 CDI cases. Per Protocol-3 analysis population included all randomised subjects who received dose 1, dose 2, and dose 3 of investigational product to which they were randomised and had no major protocol violations up to and including 14 days after dose 3. Here, “Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Primary
    End point timeframe
    From 14 days after Dose 3 to the end of the surveillance period (mean follow-up after dose 3 was 34.2 months)
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    7707
    7805
    Units: Episodes
    17
    25
    Statistical analysis title
    		 Clostridium difficile vaccine versus Placebo
    Statistical analysis description
    Vaccine efficacy(VE)=100*(1-infection rate ratio[IRR]),IRR=calculated ratio of first primary CDI incidence between Clostridium difficile vaccine group and placebo group. 96.4% CI was estimated using Clopper-Pearson-Method
    Comparison groups
    Clostridium difficile Vaccine v Placebo
    Number of subjects included in analysis
    15512
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    Method
    Parameter type
    		 Vaccine efficacy
    Point estimate
    31
    Confidence interval
         level
    		 96.4%
         sides
    2-sided
         lower limit
    		 -38.7
         upper limit
    		 66.6
    Notes
    [1] - Lower bound of confidence interval greater than 20% demonstrate vaccine efficacy.

    Primary: Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 2

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    End point title
    		 Number of First Primary Episodes of Clostridium Difficile Infection (CDI) (Definition 1) Follow-up After Dose 2
    End point description
    CDI definition 1 for primary episode of CDI(no previous CDI onset in prior 8 weeks) defined as either a)presence of diarrhea(passage of 3 or more unformed stools[Bristol stool chart types 5-7]) in 24 or fewer consecutive hours, and stool sample positive for toxin B gene(by polymerase chain reaction [PCR)] and positive for toxin A and/or toxin B, as measured in central laboratory; or b)Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample positive for toxin B gene (via PCR) as measured in central laboratory. End of surveillance period was defined as accumulation of at least 40 CDI cases. Per Protocol-2 analysis population included all randomised subjects who received dose 1 and dose 2 of the investigational product to which they were randomized and had no major protocol violations up to and including 14 days after dose 2. Here,“Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Primary
    End point timeframe
    From 14 days after Dose 2 to the end of the surveillance period (mean follow-up after dose 2 was 36 months)
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    8139
    8184
    Units: Episodes
    24
    34
    Statistical analysis title
    		 Clostridium difficile vaccine versus Placebo
    Statistical analysis description
    Vaccine efficacy(VE)=100*(1-infection rate ratio[IRR]),IRR=calculated ratio of first primary CDI incidence between Clostridium difficile vaccine group and placebo group. 96.4% CI was estimated using Clopper-Pearson-Method.
    Comparison groups
    Clostridium difficile Vaccine v Placebo
    Number of subjects included in analysis
    16323
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    Method
    Parameter type
    		 Vaccine efficacy
    Point estimate
    28.6
    Confidence interval
         level
    		 96.4%
         sides
    2-sided
         lower limit
    		 -28.4
         upper limit
    		 61
    Notes
    [2] - Lower bound of confidence interval greater than 20% demonstrate vaccine efficacy.

    Primary: Percentage of Subjects Reporting Local Reactions (LR) Within 7 Days After Dose 1

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    End point title
    		 Percentage of Subjects Reporting Local Reactions (LR) Within 7 Days After Dose 1 [3]
    End point description
    Local reactions included redness, swelling and pain at injection site. These were recorded by subjects in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. One measuring device unit= 0.5 centimeter (cm) and graded as mild: 2.5 to 5.0 cm, moderate: greater than (>) 5.0 to 10.0 cm, severe: >10.0 cm. Grade 4 indicated necrosis or exfoliative dermatitis for redness and necrosis for swelling. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity. Grade 4 indicated emergency room visit or hospitalisation. Safety analysis population included all subjects who received at least 1 dose of the investigational product. Here, “Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 1 at Month 0
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned for this endpoint.
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    8558
    8510
    Units: Percentage of subjects
    number (confidence interval 95%)
        Redness: Mild
    1.5 (1.3 to 1.8)
    0.6 (0.4 to 0.7)
        Redness: Moderate
    0.5 (0.4 to 0.7)
    0.3 (0.2 to 0.4)
        Redness: Severe
    0.4 (0.3 to 0.6)
    0.2 (0.1 to 0.3)
        Redness: Grade 4
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Swelling: Mild
    1.5 (1.3 to 1.8)
    0.5 (0.3 to 0.7)
        Swelling: Moderate
    0.9 (0.8 to 1.2)
    0.3 (0.2 to 0.5)
        Swelling: Severe
    0.3 (0.2 to 0.5)
    0.1 (0.0 to 0.2)
        Swelling: Grade 4
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Pain at injection site: Mild
    17.5 (16.7 to 18.3)
    6.2 (5.7 to 6.8)
        Pain at injection site: Moderate
    2.2 (1.9 to 2.5)
    0.8 (0.6 to 1.0)
        Pain at injection site: Severe
    0.1 (0.0 to 0.2)
    0.1 (0.1 to 0.2)
        Pain at injection site: Grade 4
    0 (0.0 to 0.0)
    0.1 (0.0 to 0.1)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Local Reactions (LR) Within 7 Days After Dose 2

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    End point title
    		 Percentage of Subjects Reporting Local Reactions (LR) Within 7 Days After Dose 2 [4]
    End point description
    Local reactions included redness, swelling and pain at injection site. These were recorded by subjects in an e-diary. Redness and swelling were measured and recorded in measuring device units. One measuring device unit= 0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: > 5.0 to 10.0 cm, severe: >10.0 cm. Grade 4 indicated necrosis or exfoliative dermatitis for redness and necrosis for swelling. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity. Grade 4 indicated emergency room visit or hospitalisation. Safety analysis population included all subjects who received at least 1 dose of the investigational product. Here, “Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 2 at Month 1
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned for this endpoint.
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    8041
    8039
    Units: Percentage of subjects
    number (confidence interval 95%)
        Redness: Mild
    2.6 (2.2 to 2.9)
    0.3 (0.2 to 0.5)
        Redness: Moderate
    2.2 (1.9 to 2.6)
    0.2 (0.1 to 0.3)
        Redness: Severe
    0.9 (0.7 to 1.2)
    0.1 (0.0 to 0.1)
        Redness: Grade 4
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Swelling: Mild
    3.2 (2.8 to 3.6)
    0.3 (0.2 to 0.53)
        Swelling: Moderate
    3.0 (2.6 to 3.4)
    0.2 (0.1 to 0.3)
        Swelling: Severe
    0.9 (0.7 to 1.1)
    0.1 (0.0 to 0.2)
        Swelling: Grade 4
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Pain at injection site: Mild
    23.0 (22.1 to 23.9)
    4.3 (3.9 to 4.8)
        Pain at injection site: Moderate
    4.5 (4.0 to 4.9)
    0.7 (0.5 to 0.9)
        Pain at injection site: Severe
    0.2 (0.1 to 0.3)
    0.1 (0.0 to 0.1)
        Pain at injection site: Grade 4
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Local Reactions (LR) Within 7 Days After Dose 3

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    End point title
    		 Percentage of Subjects Reporting Local Reactions (LR) Within 7 Days After Dose 3 [5]
    End point description
    Local reactions included redness, swelling and pain at injection site. These were recorded by subjects in an e-diary. Redness and swelling were measured and recorded in measuring device units. One measuring device unit= 0.5 cm and graded as mild: 2.5 to 5.0 cm, moderate: > 5.0 to 10.0 cm, severe: >10.0 cm. Grade 4 indicated necrosis or exfoliative dermatitis for redness and necrosis for swelling. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity. Grade 4 indicated emergency room visit or hospitalisation. Safety analysis population included all subjects who received at least 1 dose of the investigational product. Here, “Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 3 at Month 6
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned for this endpoint.
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    7526
    7569
    Units: Percentage of subjects
    number (confidence interval 95%)
        Redness: Mild
    2.6 (2.3 to 3.0)
    0.4 (0.2 to 0.5)
        Redness: Moderate
    2.4 (2.1 to 2.8)
    0.2 (0.1 to 0.4)
        Redness: Severe
    0.7 (0.5 to 0.9)
    0.1 (0.0 to 0.1)
        Redness: Grade 4
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Swelling: Mild
    3.5 (3.1 to 3.9)
    0.3 (0.2 to 0.5)
        Swelling: Moderate
    3.3 (2.9 to 3.7)
    0.2 (0.1 to 0.4)
        Swelling: Severe
    0.8 (0.6 to 1.1)
    0 (0.0 to 0.0)
        Swelling: Grade 4
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Pain at injection site: Mild
    21.0 (20.1 to 21.9)
    3.6 (3.2 to 4.1)
        Pain at injection site: Moderate
    4.5 (4.0 to 5.0)
    0.8 (0.6 to 1.0)
        Pain at injection site: Severe
    0.2 (0.1 to 0.4)
    0.1 (0.0 to 0.1)
        Pain at injection site: Grade 4
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Systemic Events (SE) Within 7 Days After Dose 1

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    End point title
    		 Percentage of Subjects Reporting Systemic Events (SE) Within 7 Days After Dose 1 [6]
    End point description
    Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by subjects in an e-diary. Fever was categorised as: mild: (38.0 to 38.4 degree Celsius [deg C]), moderate: (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C), potentially life threatening (> 40.0 deg C). Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalisation. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: >2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalisation for hypotensive shock. Safety analysis population included all subjects who received at least 1 dose of the investigational product. Here, “Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 1 at Month 0
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned for this endpoint.
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    8558
    8510
    Units: Percentage of subjects
    number (confidence interval 95%)
        Headache: Mild
    11.6 (10.9 to 12.3)
    10.1 (9.4 to 10.7)
        Headache: Moderate
    5.8 (5.3 to 6.3)
    5.4 (4.9 to 5.9)
        Headache: Severe
    0.5 (0.4 to 0.7)
    0.6 (0.5 to 0.8)
        Headache: Grade 4
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Vomiting: Mild
    1.1 (0.8 to 1.3)
    0.7 (0.5 to 0.9)
        Vomiting: Moderate
    0.3 (0.2 to 0.4)
    0.2 (0.1 to 0.3)
        Vomiting: Severe
    0.1 (0.0 to 0.1)
    0.1 (0.0 to 0.1)
        Vomiting: Grade 4
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        New or worsening muscle pain: Mild
    5.2 (4.7 to 5.7)
    3.9 (3.5 to 4.3)
        New or worsening muscle pain: Moderate
    5.7 (5.2 to 6.2)
    5.6 (5.1 to 6.1)
        New or worsening muscle pain: Severe
    0.6 (0.4 to 0.8)
    0.6 (0.5 to 0.8)
        New or worsening muscle pain: Grade 4
    0.1 (0.0 to 0.1)
    0 (0.0 to 0.0)
        New or worsening joint pain: Mild
    4.0 (3.6 to 4.5)
    3.3 (2.9 to 3.7)
        New or worsening joint pain: Moderate
    5.2 (4.7 to 5.7)
    5.0 (4.5 to 5.5)
        New or worsening joint pain: Severe
    0.5 (0.4 to 0.7)
    0.5 (0.3 to 0.6)
        New or worsening joint pain: Grade 4
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Fever: 38.0-38.4 deg C
    0.5 (0.3 to 0.6)
    0.4 (0.3 to 0.5)
        Fever: 38.5-38.9 deg C
    0.2 (0.1 to 0.3)
    0.2 (0.1 to 0.3)
        Fever: 39.0-40.0 deg C
    0.2 (0.1 to 0.3)
    0.1 (0.1 to 0.2)
        Fever: >40.0 deg C
    0.1 (0.0 to 0.2)
    0.1 (0.0 to 0.2)
        Fatigue: Mild
    11.6 (10.9 to 12.3)
    10.2 (9.6 to 10.9)
        Fatigue: Moderate
    10.6 (10.0 to 11.3)
    10.4 (9.7 to 11.0)
        Fatigue: Severe
    1.1 (0.9 to 1.3)
    1.2 (1.0 to 1.5)
        Fatigue: Grade 4
    0.1 (0.0 to 0.1)
    0 (0.0 to 0.0)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Systemic Events (SE) Within 7 Days After Dose 2

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    End point title
    		 Percentage of Subjects Reporting Systemic Events (SE) Within 7 Days After Dose 2 [7]
    End point description
    Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by subjects in an e-diary. Fever was categorised as: mild: (38.0 to 38.4 deg C), moderate: (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C), potentially life threatening (> 40.0 deg C). Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalisation. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: >2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalisation for hypotensive shock. Safety analysis population included all subjects who received at least 1 dose of the investigational product. Here, “Number of Subjects Analysed” signifies subjects evaluable for this end point and ‘’number analysed’’ signifies subjects evaluable for specific rows.
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 2 at Month 1
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned for this endpoint.
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    8041
    8039
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fatigue: Mild(n=8041, 8039)
    10.2 (9.6 to 10.9)
    7.8 (7.2 to 8.4)
        Fatigue: Moderate(n=8041, 8039)
    9.4 (8.7 to 10.0)
    9.0 (8.4 to 9.6)
        Fatigue: Severe(n=8041, 8039)
    1.0 (0.8 to 1.2)
    1.0 (0.8 to 1.2)
        Fatigue: Grade 4(n=8041, 8039)
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Headache: Mild(n=8041, 8039)
    10.1 (9.4 to 10.8)
    8.3 (7.7 to 9.0)
        Headache: Moderate(n=8041, 8039)
    5.1 (4.6 to 5.6)
    5.5 (5.0 to 6.1)
        Headache: Severe(n=8041, 8039)
    0.5 (0.4 to 0.7)
    0.4 (0.3 to 0.6)
        Headache: Grade 4(n=8041, 8039)
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Vomiting: Mild(n=8041, 8039)
    0.8 (0.6 to 1.0)
    0.7 (0.5 to 0.9)
        Vomiting: Moderate(n=8041, 8039)
    0.2 (0.1 to 0.4)
    0.2 (0.1 to 0.3)
        Vomiting: Severe(n=8041, 8039)
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Vomiting: Grade 4(n=8041, 8039)
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        New or worsening muscle pain:Mild(n=8041,8039)
    4.8 (4.3 to 5.3)
    3.2 (2.9 to 3.6)
        New or worsening muscle pain:Moderate(n=8041,8039)
    5.1 (4.6 to 5.6)
    4.2 (3.8 to 4.7)
        New or worsening muscle pain:Severe(n=8041,8039)
    0.5 (0.4 to 0.7)
    0.6 (0.4 to 0.8)
        New or worsening muscle pain:Grade 4(n=8041,8039)
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        New or worsening joint pain: Mild(n=8041, 8039)
    3.8 (3.4 to 4.2)
    2.9 (2.6 to 3.3)
        New or worsening joint pain:Moderate(n=8041,8039)
    4.6 (4.1 to 5.0)
    3.9 (3.5 to 4.4)
        New or worsening joint pain:Severe(n=8041,8039)
    0.4 (0.3 to 0.6)
    0.5 (0.3 to 0.6)
        New or worsening joint pain:Grade 4(n=8041,8039)
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Fever: 38.0-38.4 deg C(n=8041,8038)
    0.4 (0.3 to 0.6)
    0.4 (0.3 to 0.6)
        Fever: 38.5-38.9 deg C(n=8041,8038)
    0.2 (0.1 to 0.3)
    0.1 (0.0 to 0.2)
        Fever: 39.0-40.0 deg C(n=8041,8038)
    0.1 (0.0 to 0.2)
    0.2 (0.1 to 0.3)
        Fever: >40.0 deg C(n=8041, 8038)
    0.1 (0.0 to 0.1)
    0.1 (0.0 to 0.1)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Systemic Events (SE) Within 7 Days After Dose 3

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    End point title
    		 Percentage of Subjects Reporting Systemic Events (SE) Within 7 Days After Dose 3 [8]
    End point description
    Systemic events included fever, fatigue, headache, joint pain, muscle pain and vomiting. These were recorded by subjects in an e-diary. Fever was categorised as: mild: (38.0 to 38.4 deg C), moderate: (38.5 to 38.9 deg C), severe (39.0 to 40.0 deg C), potentially life threatening (> 40.0 deg C). Fatigue, headache, joint pain and muscle pain were graded as mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily activity, grade 4: emergency room visit or hospitalisation. Vomiting was graded as mild: 1 to 2 times in 24 hours, moderate: >2 times in 24 hours, severe: required intravenous hydration, grade 4: emergency room visit or hospitalisation for hypotensive shock. Safety analysis population included all subjects who received at least 1 dose of the investigational product. Here, “Number of Subjects Analysed” signifies subjects evaluable for this end point and ‘’number analysed’’ signifies subjects evaluable for specific rows.
    End point type
    Primary
    End point timeframe
    Within 7 days after Dose 3 at Month 6
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned for this endpoint.
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    7526
    7569
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fatigue: Mild(n=7526,7569)
    9.2 (8.6 to 9.9)
    7.0 (6.4 to 7.6)
        Fatigue: Moderate(n=7526,7569)
    9.4 (8.7 to 10.0)
    8.0 (7.4 to 8.6)
        Fatigue: Severe(n=7526,7569)
    0.8 (0.6 to 1.0)
    0.8 (0.6 to 1.0)
        Fatigue: Grade 4(n=7526,7569)
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Headache: Mild(n=7526,7569)
    8.4 (7.8 to 9.0)
    7.9 (7.3 to 8.5)
        Headache: Moderate(n=7526,7569)
    5.7 (5.1 to 6.2)
    4.7 (4.2 to 5.2)
        Headache: Severe(n=7526,7569)
    0.3 (0.2 to 0.5)
    0.5 (0.3 to 0.6)
        Headache: Grade 4(n=7526,7569)
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Vomiting: Mild(n=7526,7569)
    0.6 (0.5 to 0.8)
    0.5 (0.4 to 0.7)
        Vomiting: Moderate(n=7526,7569)
    0.1 (0.0 to 0.2)
    0.2 (0.1 to 0.3)
        Vomiting: Severe(n=7526,7569)
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        Vomiting: Grade 4(n=7526,7569)
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        New or worsening muscle pain:Mild(n=7526,7569)
    4.0 (3.5 to 4.4)
    2.5 (2.2 to 2.9)
        New or worsening muscle pain:Moderate(n=7526,7569)
    4.8 (4.3 to 5.3)
    4.1 (3.6 to 4.6)
        New or worsening muscle pain:Severe(n=7526,7569)
    0.5 (0.3 to 0.7)
    0.5 (0.3 to 0.7)
        New or worsening muscle pain:Grade 4(n=7526,7569)
    0 (0.0 to 0.0)
    0 (0.0 to 0.0)
        New or worsening joint pain:Mild(n=7526,7569)
    3.0 (2.6 to 3.4)
    2.5 (2.2 to 2.9)
        New or worsening joint pain:Moderate(n=7526,7569)
    4.4 (3.9 to 4.8)
    3.6 (3.2 to 4.0)
        New or worsening joint pain:Severe(n=7526,7569)
    0.4 (0.3 to 0.6)
    0.4 (0.3 to 0.5)
        New or worsening joint pain:Grade 4(n=7526,7569)
    0.1 (0.0 to 0.1)
    0 (0.0 to 0.0)
        Fever: 38.0-38.4 deg C(n=7525,7569)
    0.4 (0.3 to 0.6)
    0.2 (0.1 to 0.4)
        Fever: 38.5-38.9 deg C(n=7525,7569)
    0.1 (0.1 to 0.2)
    0.1 (0.0 to 0.2)
        Fever: 39.0-40.0 deg C(n=7525,7569)
    0.1 (0.1 to 0.2)
    0.1 (0.0 to 0.2)
        Fever: >40.0 deg C(n=7525,7569)
    0.1 (0.0 to 0.1)
    0.1 (0.1 to 0.2)
    No statistical analyses for this end point

    Primary: Number of Subjects Reporting Adverse Events (AEs)

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    End point title
    		 Number of Subjects Reporting Adverse Events (AEs) [9]
    End point description
    An AE was defined as any untoward medical occurrence in a subjects who received investigational product without regard to possibility of causal relationship. AEs included both serious and all non-serious adverse events. An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening (immediate risk of death); required inpatient hospitalisation or prolongation of existing hospitalisation; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect; or that was considered as an important medical event. AEs included both SAEs and all Non-SAEs (except local and systemic events). Safety analysis population included all subjects who received at least 1 dose of the investigational product.
    End point type
    Primary
    End point timeframe
    From Day 1 of Dose 1 to 1 Month after Dose 3 (7 Months)
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned for this endpoint.
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    8722
    8718
    Units: Subjects
        Any AEs
    4161
    4050
        Non-Serious AEs
    3913
    3791
    No statistical analyses for this end point

    Primary: Number of Subjects Reporting Serious Adverse Events (SAEs)

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    End point title
    		 Number of Subjects Reporting Serious Adverse Events (SAEs) [10]
    End point description
    An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening (immediate risk of death); required inpatient hospitalisation or prolongation of existing hospitalisation; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect; or that was considered as an important medical event. Safety analysis population included all participants who received at least 1 dose of the investigational product.
    End point type
    Primary
    End point timeframe
    From Day 1 of Dose 1 up to 6 months after Dose 3 (up to Month 12)
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned for this endpoint.
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    8722
    8718
    Units: Subjects
    719
    722
    No statistical analyses for this end point

    Secondary: Number of all Episodes of CDI (Definition 1 and 2) After Dose 3

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    End point title
    		 Number of all Episodes of CDI (Definition 1 and 2) After Dose 3
    End point description
    CDI definition 1 for primary episode of CDI(no previous CDI onset in prior 8 weeks),CDI definition 2 for recurrent episode(episode occurred 8 weeks or less after onset of previous episode[provided symptoms of previous episode resolved])were both defined as either a)presence of diarrhea,(passage of 3 or more unformed stools[Bristol stool chart types 5-7])in 24 or fewer consecutive hours,stool sample positive for toxin B gene(by PCR),positive for toxin A and/or B,measured in central laboratory;or b)Pseudomembranous colitis diagnosed at colonoscopy, surgery, histopathologically; corresponding stool sample positive for toxin B gene(via PCR)measured in central laboratory.Per Protocol-3 analysis population included all randomised subjects who received dose 1, dose 2, and dose 3 of investigational product to which they were randomized had no major protocol violations up to and including 14 days after dose 3. Here,“Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    From 14 days after Dose 3 to the end of the surveillance period (mean follow-up after dose 3 was 34.2 months)
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    7707
    7805
    Units: Episodes
    28
    32
    Statistical analysis title
    		 Clostridium difficile vaccine versus Placebo
    Statistical analysis description
    VE = 100*(1 - Hazard Ratio). 98.2% CI was estimated using Proportional Means Model.
    Comparison groups
    Clostridium difficile Vaccine v Placebo
    Number of subjects included in analysis
    15512
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Vaccine efficacy
    Point estimate
    11.1
    Confidence interval
         level
    		 98.2%
         sides
    2-sided
         lower limit
    		 -110.7
         upper limit
    		 62.5

    Secondary: Time to Resolution for Subjects With First Primary Episodes of CDI (Definition 1) After Dose 3

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    End point title
    		 Time to Resolution for Subjects With First Primary Episodes of CDI (Definition 1) After Dose 3
    End point description
    Resolution of event was last day on which event was recorded in e-diary or date the event ends if it was unresolved during subject diary-recording period(end date collected on case report form[CRF]).CDI definition 1 for primary episode of CDI(no previous CDI onset in prior 8 weeks) defined as either a)presence of diarrhea(passage of 3 or more unformed stools[Bristol stool chart types 5-7]) in 24 or fewer consecutive hours, and stool sample positive for toxin B gene(by polymerase chain reaction [PCR)] and positive for toxin A and/or toxin B, as measured in central laboratory; or b)Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample positive for toxin B gene (via PCR) as measured in central laboratory. End of surveillance period was defined as accumulation of at least 40 CDI cases. Per Protocol-3 analysis population was analysed. Here,“Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    From 14 days after Dose 3 to the end of the surveillance period (mean follow-up after dose 3 was 34.2 months)
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    17
    24
    Units: Days
        median (full range (min-max))
    1.0 (1 to 18)
    4.0 (1 to 183)
    Statistical analysis title
    		 Clostridium difficile vaccine versus Placebo
    Comparison groups
    Clostridium difficile Vaccine v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0172
    Method
    		 Wilcoxon Rank Sum Test (2-sided)
    Confidence interval

    Secondary: Proportion of Subjects who Required Medical Attention During First Primary Episode of CDI (Definition 1) After Dose 3

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    End point title
    		 Proportion of Subjects who Required Medical Attention During First Primary Episode of CDI (Definition 1) After Dose 3
    End point description
    CDI definition 1 for a primary episode of CDI(no previous CDI onset in prior 8 weeks) defined as either a) presence of diarrhea, defined as passage of 3 or more unformed stools (Bristol stool chart types 5-7) in 24 or fewer consecutive hours, and stool sample that was positive for toxin B gene (by PCR) and positive for toxin A and/or toxin B, as measured in central laboratory; or b)Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample that was positive for toxin B gene (via PCR) as measured in central laboratory.End of surveillance period was defined as accumulation of at least 40 CDI cases.Per Protocol-3 analysis population included all randomised subjects who received dose 1,dose 2,and dose 3 of the investigational product to which they were randomised and had no major protocol violations up to and including 14 days after dose 3. Here,“Overall Number of Subjects Analyzed”signifies subjects evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    From 14 days after Dose 3 to the end of the surveillance period (mean follow-up after dose 3 was 34.2 months)
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    17
    25
    Units: Proportion of subjects
        number (not applicable)
    0
    0.440
    Statistical analysis title
    		 Clostridium difficile vaccine versus Placebo
    Comparison groups
    Clostridium difficile Vaccine v Placebo
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Ratio of proportions
    Point estimate
    0
    Confidence interval
         level
    		 98.2%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.81

    Secondary: Number of Subjects With Recurrent Episodes of CDI (Definition 2) After Dose 3

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    End point title
    		 Number of Subjects With Recurrent Episodes of CDI (Definition 2) After Dose 3
    End point description
    CDI definition 2 for recurrent episode(an episode of CDI that occurred 8 weeks or less after onset of a previous CDI episode[provided symptoms of previous episode had resolved]),defined as either a)presence of diarrhea(passage of 3 or more unformed stools[Bristol stool chart types 5-7])in 24 or fewer consecutive hours; stool sample that was positive for toxin B gene (by PCR) and positive for toxin A and/or toxin B, as measured in central laboratory; or b) Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample that was positive for toxin B gene (by PCR) as measured in central laboratory. Per Protocol-3 analysis population included all randomised subjects who received dose 1, dose 2, and dose 3 of the investigational product to which they were randomised and had no major protocol violations up to and including 14 days after dose 3. Here, “Overall Number of Subjects Analyzed” signifies subjects evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    From 14 days after Dose 3 to the end of the surveillance period (mean follow-up after dose 3 was 34.2 months)
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    7707
    7805
    Units: Subjects
    5
    3
    Statistical analysis title
    		 Clostridium difficile vaccine versus Placebo
    Statistical analysis description
    Vaccine efficacy(VE)=100*(1-infection rate ratio[IRR]),IRR=calculated ratio of recurrent CDI incidence between Clostridium difficile vaccine group and placebo group. 98.2% CI was estimated using Clopper-Pearson-Method.
    Comparison groups
    Clostridium difficile Vaccine v Placebo
    Number of subjects included in analysis
    15512
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Vaccine efficacy
    Point estimate
    -69.3
    Confidence interval
         level
    		 98.2%
         sides
    2-sided
         lower limit
    		 -1533.1
         upper limit
    		 75.6

    Secondary: Number of all Episodes of CDI (Definition 1 and 2) After Dose 2

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    End point title
    		 Number of all Episodes of CDI (Definition 1 and 2) After Dose 2
    End point description
    CDI definition 1 for primary episode of CDI(no previous CDI onset in prior 8 weeks),CDI definition 2 for recurrent episode(episode occurred 8 weeks or less after onset of previous episode[provided symptoms of previous episode resolved])were both defined as either a)presence of diarrhea,(passage of 3 or more unformed stools[Bristol stool chart types 5-7])in 24 or fewer consecutive hours,stool sample positive for toxin B gene(by PCR),positive for toxin A and/or B,measured in central laboratory;or b)Pseudomembranous colitis diagnosed at colonoscopy, surgery, histopathologically; corresponding stool sample positive for toxin B gene(via PCR)measured in central laboratory. Per Protocol-2 analysis population included all randomised subjects who received dose 1 and dose 2 of the investigational product to which they were randomized and had no major protocol violations up to and including 14 days after dose 2. Here,“Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    From 14 days after Dose 2 to the end of the surveillance period (mean follow-up after dose 2 was 36 months)
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    8139
    8184
    Units: Episodes
    37
    44
    Statistical analysis title
    		 Clostridium difficile vaccine versus Placebo
    Statistical analysis description
    VE = 100*(1 - Hazard Ratio). 98.2% CI was estimated using Proportional Means Model
    Comparison groups
    Clostridium difficile Vaccine v Placebo
    Number of subjects included in analysis
    16323
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Vaccine efficacy
    Point estimate
    14.9
    Confidence interval
         level
    		 98.2%
         sides
    2-sided
         lower limit
    		 -74.6
         upper limit
    		 58.5

    Secondary: Number of Subjects With Recurrent Episodes of CDI (Definition 2) After Dose 2

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    End point title
    		 Number of Subjects With Recurrent Episodes of CDI (Definition 2) After Dose 2
    End point description
    CDI definition 2 for recurrent episode(an episode of CDI that occurred 8 weeks or less after onset of a previous CDI episode[provided symptoms of previous episode had resolved]),defined as either a)presence of diarrhea(passage of 3 or more unformed stools[Bristol stool chart types 5-7])in 24 or fewer consecutive hours; stool sample that was positive for toxin B gene (by PCR) and positive for toxin A and/or toxin B, as measured in central laboratory; or b) Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample that was positive for toxin B gene (by PCR) as measured in central laboratory. Per Protocol-2 analysis population included all randomised subjects who received dose 1 and dose 2 of the investigational product to which they were randomized and had no major protocol violations up to and including 14 days after dose 2. Here,“Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    From 14 days after Dose 2 to the end of the surveillance period (mean follow-up after dose 2 was 36 months)
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    8139
    8184
    Units: Subjects
    6
    3
    Statistical analysis title
    		 Clostridium difficile vaccine versus Placebo
    Statistical analysis description
    VE = 100*(1 - IRR), where IRR= the calculated ratio of recurrent CDI incidence between the Clostridium difficile vaccine group and the placebo group. 98.2% CI was estimated using Clopper-Pearson-Method.
    Comparison groups
    Clostridium difficile Vaccine v Placebo
    Number of subjects included in analysis
    16323
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Vaccine efficacy
    Point estimate
    -102.4
    Confidence interval
         level
    		 98.2%
         sides
    2-sided
         lower limit
    		 -1770.1
         upper limit
    		 67.2

    Secondary: Number of First Primary Episode of CDI (Definition 1) After Dose 2 and Before Dose 3

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    End point title
    		 Number of First Primary Episode of CDI (Definition 1) After Dose 2 and Before Dose 3
    End point description
    CDI definition 1 for a primary episode of CDI (no previous CDI onset in the prior 8 weeks) was defined as either a) presence of diarrhea, defined as passage of 3 or more unformed stools (Bristol stool chart types 5-7) in 24 or fewer consecutive hours, and stool sample that was positive for the toxin B gene (by PCR) and positive for toxin A and/or toxin B, as measured in the central laboratory; or b) Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample that was positive for the toxin B gene (via PCR) as measured in the central laboratory. Per Protocol-2 analysis population included all randomised subjects who received dose 1 and dose 2 of the investigational product to which they were randomized and had no major protocol violations up to and including 14 days after dose 2. Here,“Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    From 14 days after Dose 2 to Dose 3 or the day the third vaccination was expected (168 days after Dose 2) for subjects who received only 2 doses
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    8139
    8184
    Units: Episodes
    7
    8
    Statistical analysis title
    		 Clostridium difficile vaccine versus Placebo
    Statistical analysis description
    Vaccine efficacy(VE)=100*(1-infection rate ratio[IRR]),IRR=calculated ratio of first primary CDI incidence between Clostridium difficile vaccine group and placebo group. 98.2% CI was estimated using Clopper-Pearson-Method.
    Comparison groups
    Clostridium difficile Vaccine v Placebo
    Number of subjects included in analysis
    16323
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Vaccine efficacy
    Point estimate
    12
    Confidence interval
         level
    		 98.2%
         sides
    2-sided
         lower limit
    		 -246.7
         upper limit
    		 78.5

    Secondary: Number of Subjects With Recurrent Episode of CDI (Definition 2) After Dose 2 and Before Dose 3

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    End point title
    		 Number of Subjects With Recurrent Episode of CDI (Definition 2) After Dose 2 and Before Dose 3
    End point description
    CDI definition 2 for recurrent episode(an episode of CDI that occurred 8 weeks or less after onset of a previous CDI episode[provided symptoms of previous episode had resolved]),defined as either a)presence of diarrhea(passage of 3 or more unformed stools[Bristol stool chart types 5-7])in 24 or fewer consecutive hours; stool sample that was positive for toxin B gene (by PCR) and positive for toxin A and/or toxin B, as measured in central laboratory; or b) Pseudomembranous colitis diagnosed at colonoscopy, at surgery, or histopathologically; and corresponding stool sample that was positive for toxin B gene (by PCR) as measured in central laboratory. Per Protocol-2 analysis population included all randomised subjects who received dose 1 and dose 2 of the investigational product to which they were randomized and had no major protocol violations up to and including 14 days after dose 2. Here,“Number of Subjects Analysed” signifies subjects evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    From 14 days after Dose 2 to Dose 3 or the day the third vaccination was expected (168 days after Dose 2) for subjects who received only 2 doses
    End point values
    		 Clostridium difficile Vaccine Placebo
    Number of subjects analysed
    8139
    8184
    Units: Subjects
    1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    LR and SE(added in otherAEs):within 7days after each dose(systematic assessment);SAEs:Day1upto 6months after last dose(up to12months);other AEs:Day1upto1month after last dose(upto7months);All-Cause mortality:Day1 upto 6months after last dose(upto12months)
    Adverse event reporting additional description
    Same event may appear as both an AE and SAE. However,what is presented are distinct events.An event may be categorised as serious in one subject and non-serious in another,or a subject may have experienced both a serious and non-serious event.Safety analysis population included all subjects who received at least 1 dose of investigational product.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Clostridium difficile Vaccine
    Reporting group description
    		 Participants were randomized to receive a single dose of Clostridium difficile vaccine 200 microgram total toxoid per dose intramuscularly at Months 0, 1 and 6.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants were randomized to receive a single dose of placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly at Months 0, 1 and 6.

    Serious adverse events
    		 Clostridium difficile Vaccine Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    719 / 8722 (8.24%)
    722 / 8718 (8.28%)
         number of deaths (all causes)
    369
    362
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma gastric
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    B-cell small lymphocytic lymphoma stage III
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    3 / 8722 (0.03%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign breast neoplasm
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign neoplasm of bladder
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer recurrent
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 8722 (0.01%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Breast cancer
         subjects affected / exposed
    2 / 8722 (0.02%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangiocarcinoma
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer metastatic
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Endometrial cancer recurrent
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cancer
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Intestinal metastasis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Intraductal proliferative breast lesion
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal cancer
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    4 / 8722 (0.05%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung carcinoma cell type unspecified stage IV
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to abdominal cavity
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to lung
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Metastases to lymph nodes
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Metastases to peritoneum
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myxofibrosarcoma
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine carcinoma
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer metastatic
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal cancer metastatic
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Oesophageal squamous cell carcinoma
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cancer metastatic
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal neoplasm
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pituitary tumour benign
         subjects affected / exposed
    0 / 8722 (0.00%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer metastatic
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Prostate cancer stage I
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    7 / 8722 (0.08%)
    7 / 8718 (0.08%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Rectal cancer
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin cancer
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 8722 (0.00%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric cancer
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Accelerated hypertension
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    3 / 8722 (0.03%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Aortic stenosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Arterial occlusive disease
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    2 / 8722 (0.02%)
    7 / 8718 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Diabetic vascular disorder
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Extremity necrosis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemodynamic instability
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    2 / 8722 (0.02%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hypertensive crisis
         subjects affected / exposed
    3 / 8722 (0.03%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    5 / 8722 (0.06%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive urgency
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    5 / 8722 (0.06%)
    8 / 8718 (0.09%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery occlusion
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 8722 (0.01%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian steal syndrome
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subclavian vein thrombosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vein disorder
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    6 / 8722 (0.07%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    25 / 8722 (0.29%)
    32 / 8718 (0.37%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 32
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Complication of device insertion
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug interaction
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug withdrawal syndrome
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothermia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    0 / 8722 (0.00%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site haematoma
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site pain
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site swelling
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    4 / 8722 (0.05%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    3 / 8722 (0.03%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pacemaker generated arrhythmia
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic mass
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Surgical failure
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sarcoidosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Social circumstances
    Physical assault
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Balanoposthitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign prostatic hyperplasia
         subjects affected / exposed
    2 / 8722 (0.02%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical dysplasia
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial hyperplasia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Female genital tract fistula
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heavy menstrual bleeding
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postmenopausal haemorrhage
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatomegaly
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    11 / 8722 (0.13%)
    12 / 8718 (0.14%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 14
         deaths causally related to treatment / all
    0 / 4
    0 / 6
    Aspiration
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    7 / 8722 (0.08%)
    6 / 8718 (0.07%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthmatic crisis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bronchospasm
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    33 / 8722 (0.38%)
    43 / 8718 (0.49%)
         occurrences causally related to treatment / all
    0 / 37
    0 / 44
         deaths causally related to treatment / all
    0 / 9
    0 / 12
    Cough
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    6 / 8722 (0.07%)
    5 / 8718 (0.06%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Epistaxis
         subjects affected / exposed
    3 / 8722 (0.03%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    3 / 8722 (0.03%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercapnia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypersensitivity pneumonitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    6 / 8722 (0.07%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nasal septum deviation
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    5 / 8722 (0.06%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    3 / 8722 (0.03%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    10 / 8722 (0.11%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    3 / 8722 (0.03%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory acidosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    9 / 8722 (0.10%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol withdrawal syndrome
         subjects affected / exposed
    0 / 8722 (0.00%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Attention deficit hyperactivity disorder
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression suicidal
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 8722 (0.01%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paranoia
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Schizoaffective disorder
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    0 / 8722 (0.00%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device loosening
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device occlusion
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lead dislodgement
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary obstruction
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cholangitis acute
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis sclerosing
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    3 / 8722 (0.03%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cholecystitis acute
         subjects affected / exposed
    3 / 8722 (0.03%)
    5 / 8718 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    3 / 8722 (0.03%)
    5 / 8718 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder rupture
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic lesion
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Anticoagulation drug level above therapeutic
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood potassium decreased
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram ST segment elevation
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heart rate increased
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal function test abnormal
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    0 / 8722 (0.00%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acetabulum fracture
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia postoperative
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    4 / 8722 (0.05%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthropod sting
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone contusion
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cartilage injury
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Combined tibia-fibula fracture
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    4 / 8722 (0.05%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Facial bones fracture
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    6 / 8722 (0.07%)
    10 / 8718 (0.11%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 8722 (0.00%)
    7 / 8718 (0.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 8722 (0.02%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fractured coccyx
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Heat exhaustion
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Heat stroke
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    3 / 8722 (0.03%)
    5 / 8718 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Humerus fracture
         subjects affected / exposed
    4 / 8722 (0.05%)
    5 / 8718 (0.06%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incision site swelling
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Intentional product misuse
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    6 / 8722 (0.07%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    2 / 8722 (0.02%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle strain
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal foreign body
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck injury
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural discharge
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematuria
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative respiratory distress
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound complication
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postpolypectomy syndrome
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    5 / 8722 (0.06%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    5 / 8722 (0.06%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    Sciatic nerve injury
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress fracture
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous haematoma
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Traumatic haemothorax
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention postoperative
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular graft thrombosis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular procedure complication
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Wound decomposition
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound evisceration
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Arnold-Chiari malformation
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial septal defect
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Corneal dystrophy
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hereditary motor and sensory neuropathy
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mobile caecum syndrome
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute left ventricular failure
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    20 / 8722 (0.23%)
    8 / 8718 (0.09%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 8
         deaths causally related to treatment / all
    0 / 6
    0 / 2
    Angina pectoris
         subjects affected / exposed
    9 / 8722 (0.10%)
    13 / 8718 (0.15%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    4 / 8722 (0.05%)
    9 / 8718 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Arrhythmia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Arteriosclerosis coronary artery
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    12 / 8722 (0.14%)
    15 / 8718 (0.17%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 17
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Atrial flutter
         subjects affected / exposed
    4 / 8722 (0.05%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    3 / 8722 (0.03%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    3 / 8722 (0.03%)
    6 / 8718 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 11
    0 / 20
    Cardiac failure acute
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    Cardiac failure chronic
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Cardiac failure congestive
         subjects affected / exposed
    14 / 8722 (0.16%)
    17 / 8718 (0.19%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 17
         deaths causally related to treatment / all
    0 / 10
    0 / 6
    Cardiac failure
         subjects affected / exposed
    13 / 8722 (0.15%)
    10 / 8718 (0.11%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 11
         deaths causally related to treatment / all
    0 / 9
    0 / 8
    Cardio-respiratory arrest
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 5
    Cardiogenic shock
         subjects affected / exposed
    3 / 8722 (0.03%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 4
    Cardiovascular disorder
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery disease
         subjects affected / exposed
    13 / 8722 (0.15%)
    8 / 8718 (0.09%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 8
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    Coronary artery insufficiency
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    5 / 8718 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    12 / 8722 (0.14%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 4
         deaths causally related to treatment / all
    0 / 14
    0 / 8
    Myocardial injury
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    2 / 8722 (0.02%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulseless electrical activity
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus arrest
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    3 / 8722 (0.03%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    2 / 8722 (0.02%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    2 / 8722 (0.02%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Balance disorder
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain injury
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Carotid artery disease
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery occlusion
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar haemorrhage
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar infarction
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebral artery stenosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebrovascular accident
         subjects affected / exposed
    11 / 8722 (0.13%)
    7 / 8718 (0.08%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 7
         deaths causally related to treatment / all
    0 / 11
    0 / 1
    Cerebrovascular disorder
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular insufficiency
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cervical radiculopathy
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia Alzheimer's type
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic hyperosmolar coma
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    3 / 8722 (0.03%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    4 / 8722 (0.05%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive encephalopathy
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    6 / 8722 (0.07%)
    5 / 8718 (0.06%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    3 / 8722 (0.03%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelopathy
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurological symptom
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Occipital neuralgia
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Presyncope
         subjects affected / exposed
    2 / 8722 (0.02%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 8722 (0.02%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal stroke
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Spondylitic myelopathy
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    11 / 8722 (0.13%)
    13 / 8718 (0.15%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombotic cerebral infarction
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient global amnesia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    8 / 8722 (0.09%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wernicke-Korsakoff syndrome
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia macrocytic
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    6 / 8722 (0.07%)
    8 / 8718 (0.09%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Immune thrombocytopenia
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    3 / 8722 (0.03%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    1 / 8722 (0.01%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    3 / 8722 (0.03%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epiretinal membrane
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal vein occlusion
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vision blurred
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual impairment
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal incarcerated hernia
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    5 / 8722 (0.06%)
    6 / 8718 (0.07%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal wall haematoma
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic ulcer perforation
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Change of bowel habit
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    3 / 8722 (0.03%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterovesical fistula
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    4 / 8722 (0.05%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    3 / 8722 (0.03%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastrointestinal motility disorder
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal ulcer haemorrhage
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    2 / 8722 (0.02%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    3 / 8722 (0.03%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 8722 (0.01%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive pancreatitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal spasm
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Oesophagitis haemorrhagic
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    8 / 8722 (0.09%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pancreatitis chronic
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    2 / 8722 (0.02%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papilla of Vater stenosis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parotid gland enlargement
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer haemorrhage
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 8722 (0.02%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal prolapse
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal haemorrhage
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    2 / 8722 (0.02%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    3 / 8722 (0.03%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Varices oesophageal
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    4 / 8722 (0.05%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Blister
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulite
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decubitus ulcer
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot
         subjects affected / exposed
    2 / 8722 (0.02%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Diabetic ulcer
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lichen planus
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pemphigoid
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin disorder
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer haemorrhage
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    9 / 8722 (0.10%)
    18 / 8718 (0.21%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 19
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    Calculus urinary
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contracted bladder
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    4 / 8722 (0.05%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incontinence
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower urinary tract symptoms
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    5 / 8722 (0.06%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvi-ureteric obstruction
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal disorder
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Renal tubular necrosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcapsular renal haematoma
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral obstruction
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 8722 (0.00%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vesicoureteric reflux
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Basedow's disease
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 8722 (0.05%)
    9 / 8718 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    4 / 8722 (0.05%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthropathy
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    4 / 8722 (0.05%)
    9 / 8718 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chondropathy
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dupuytren's contracture
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture malunion
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint stiffness
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint swelling
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    2 / 8722 (0.02%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle spasms
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 8722 (0.00%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    18 / 8722 (0.21%)
    15 / 8718 (0.17%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in jaw
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudarthrosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sacral pain
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal instability
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    4 / 8722 (0.05%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondyloarthropathy
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovial disorder
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendinous contracture
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendonitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    1 / 8722 (0.01%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    2 / 8722 (0.02%)
    5 / 8718 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    3 / 8722 (0.03%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bacterial infection
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis viral
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    12 / 8722 (0.14%)
    11 / 8718 (0.13%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis infective
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    23 / 8722 (0.26%)
    18 / 8718 (0.21%)
         occurrences causally related to treatment / all
    0 / 24
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Chronic sinusitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 8722 (0.00%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis escherichia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    2 / 8722 (0.02%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    8 / 8722 (0.09%)
    7 / 8718 (0.08%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 8722 (0.01%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extradural abscess
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Folliculitis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fournier's gangrene
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture infection
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fungal infection
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gas gangrene
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    2 / 8722 (0.02%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastroenteritis
         subjects affected / exposed
    0 / 8722 (0.00%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal viral infection
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma infection
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic fever with renal syndrome
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic fever
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Helicobacter infection
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis viral
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    3 / 8722 (0.03%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    6 / 8722 (0.07%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney infection
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Listeria sepsis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    5 / 8722 (0.06%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lyme disease
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medical device site joint infection
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis bacterial
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ophthalmic herpes zoster
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oropharyngeal candidiasis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis acute
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis fungal
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    12 / 8722 (0.14%)
    11 / 8718 (0.13%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Parotitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 8722 (0.01%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    2 / 8722 (0.02%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    38 / 8722 (0.44%)
    39 / 8718 (0.45%)
         occurrences causally related to treatment / all
    0 / 40
    0 / 40
         deaths causally related to treatment / all
    0 / 5
    0 / 6
    Post procedural infection
         subjects affected / exposed
    3 / 8722 (0.03%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate infection
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 8722 (0.00%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    2 / 8722 (0.02%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyuria
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scrotal abscess
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    16 / 8722 (0.18%)
    16 / 8718 (0.18%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 16
         deaths causally related to treatment / all
    0 / 6
    0 / 3
    Septic arthritis staphylococcal
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    3 / 8722 (0.03%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal bacteraemia
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 8722 (0.01%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection enterococcal
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    13 / 8722 (0.15%)
    10 / 8718 (0.11%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Urosepsis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viraemia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulval abscess
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound abscess
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection staphylococcal
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Alcoholic ketoacidosis
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    8 / 8722 (0.09%)
    5 / 8718 (0.06%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 9
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 8722 (0.00%)
    4 / 8718 (0.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    4 / 8722 (0.05%)
    5 / 8718 (0.06%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    2 / 8722 (0.02%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    2 / 8722 (0.02%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemic hyperosmolar nonketotic syndrome
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    2 / 8722 (0.02%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypervolaemia
         subjects affected / exposed
    1 / 8722 (0.01%)
    3 / 8718 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hypoglycaemia
         subjects affected / exposed
    4 / 8722 (0.05%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    3 / 8722 (0.03%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoosmolar state
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 8722 (0.00%)
    2 / 8718 (0.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lactose intolerance
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 8722 (0.00%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 8722 (0.01%)
    0 / 8718 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 8722 (0.01%)
    1 / 8718 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Clostridium difficile Vaccine Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    5702 / 8722 (65.37%)
    4314 / 8718 (49.48%)
    Nervous system disorders
    Headache (HEADACHE)
    alternative assessment type: Systematic
         subjects affected / exposed
    2615 / 8722 (29.98%)
    2323 / 8718 (26.65%)
         occurrences all number
    2615
    2323
    General disorders and administration site conditions
    Fatigue (FATIGUE)
    alternative assessment type: Systematic
         subjects affected / exposed
    3240 / 8722 (37.15%)
    2820 / 8718 (32.35%)
         occurrences all number
    3240
    2820
    Injection site pain (PAIN)
    alternative assessment type: Systematic
         subjects affected / exposed
    3596 / 8722 (41.23%)
    1056 / 8718 (12.11%)
         occurrences all number
    3596
    1056
    Injection site swelling (SWELLING)
    alternative assessment type: Systematic
         subjects affected / exposed
    1846 / 8722 (21.16%)
    414 / 8718 (4.75%)
         occurrences all number
    1846
    414
    Skin and subcutaneous tissue disorders
    Injection site erythema (REDNESS)
    alternative assessment type: Systematic
         subjects affected / exposed
    1879 / 8722 (21.54%)
    653 / 8718 (7.49%)
         occurrences all number
    1879
    653
    Musculoskeletal and connective tissue disorders
    Arthralgia (JOINT PAIN)
    alternative assessment type: Systematic
         subjects affected / exposed
    1583 / 8722 (18.15%)
    1354 / 8718 (15.53%)
         occurrences all number
    1583
    1354
    Myalgia (MUSCLE PAIN)
    alternative assessment type: Systematic
         subjects affected / exposed
    1856 / 8722 (21.28%)
    1487 / 8718 (17.06%)
         occurrences all number
    1856
    1487

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Sep 2020
    Clarified that if an SAE was reported after subject Visit 6, all the requirements will apply, including the respect of the reporting timelines as if the SAE occurred within the reporting period.

    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.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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