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    Clinical Trial Results:
    Ensayo clínico de vacunación fase III, aleatorizado, observador-ciego, controlado con placebo, multicéntrico para evaluar la eficacia profiláctica, seguridad e inmunogenicidad de la vacuna gE/AS01B de GSK Biologicals administrada por vía intramuscular con un esquema de 0, 2 meses en adultos de 70 años y mayores.

    Summary
    EudraCT number
    2009-015791-94
    Trial protocol
    ES   FI   DE   GB   SE   EE   FR   IT   CZ  
    Global end of trial date
    24 Jul 2015

    Results information
    Results version number
    v2(current)
    This version publication date
    03 May 2020
    First version publication date
    08 Aug 2016
    Other versions
    v1
    Version creation reason
    • Correction of full data set
    Results have been amended to account for consistency with other registries.

    Trial information

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    Trial identification
    Sponsor protocol code
    113077
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02723773
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.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
    14 Jan 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Jul 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    • Zoster-022 study: To evaluate vaccine efficacy (VE) in the prevention of herpes Zoster (HZ) compared to placebo in adults ≥ 70 years of age (YOA), as measured by the reduction in HZ risk. • Zoster-006 and Zoster-022 pooled studies: To evaluate VE in the prevention of postherpetic neuralgia (PHN) compared to placebo in subjects ≥ 70 YOA across both Phase III studies. To consolidate VE estimation in the prevention of HZ compared to placebo in subjects ≥ 70 YOA across both Phase III studies.
    Protection of trial subjects
    The vaccine/product recipients were to be observed closely for at least 30 minutes, with appropriate medical treatment readily available in case of a rare anaphylactic reaction following the administration of vaccine/product. Vaccines/products were administered by qualified and trained personnel. Vaccines/products were administered only to eligible subjects that had no contraindications to any components of the vaccines/products. Subjects were followed-up for 30 days after the last vaccination/product administration.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    02 Aug 2010
    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
    United States: 1879
    Country: Number of subjects enrolled
    Australia: 309
    Country: Number of subjects enrolled
    Brazil: 627
    Country: Number of subjects enrolled
    Canada: 802
    Country: Number of subjects enrolled
    Czech Republic: 321
    Country: Number of subjects enrolled
    Estonia: 1015
    Country: Number of subjects enrolled
    Finland: 1705
    Country: Number of subjects enrolled
    France: 575
    Country: Number of subjects enrolled
    Germany: 1202
    Country: Number of subjects enrolled
    Hong Kong: 180
    Country: Number of subjects enrolled
    Italy: 109
    Country: Number of subjects enrolled
    Japan: 511
    Country: Number of subjects enrolled
    Korea, Republic of: 528
    Country: Number of subjects enrolled
    Mexico: 453
    Country: Number of subjects enrolled
    Spain: 934
    Country: Number of subjects enrolled
    Sweden: 961
    Country: Number of subjects enrolled
    Taiwan: 1110
    Country: Number of subjects enrolled
    United Kingdom: 692
    Worldwide total number of subjects
    13913
    EEA total number of subjects
    7514
    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)
    13913
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Only 13900 subjects from the total enrolled number were vaccinated and included in the Total Vaccinated Cohort. In the placebo group, 1 subject had an unknown withdrawal status before the study site closure. This was not identified during database freeze, leading to 1190 subjects in place of 1189 that actually completed the placebo group

    Pre-assignment period milestones
    Number of subjects started
    14819 [1]
    Number of subjects completed
    13900

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Eliminated from statistical analysess: 906
    Reason: Number of subjects
    No vaccination received: 13
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The number started in pre-assignment period are the number of subjects considered for enrollment. However, 906 subjects were excluded for analysis- leading to actual enrolled of 13913, which was considered as the total eligible cohort. This total eligible cohort was considered for further analysis.
    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Zoster-022 GSK1437173A Group
    Arm description
    Subjects receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK1437173A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The study product was administered according to a 0, 2 month schedule.

    Arm title
    Zoster-022 Placebo Group
    Arm description
    Subjects receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Saline solution
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    The study product was administered according to a 0, 2 month schedule.

    Number of subjects in period 1 [2]
    Zoster-022 GSK1437173A Group Zoster-022 Placebo Group
    Started
    6950
    6950
    Completed
    5770
    5760
    Not completed
    1180
    1190
         No reason from the subject
    108
    102
         Protocol deviation
    6
    8
         Migrated/moved from study area
    51
    46
         Unknown completion status
    -
    1
         Consent withdrawn by subject
    387
    396
         Non-Serious Adverse Event
    47
    15
         Serious Adverse Event
    456
    487
         Suspected HZ Episode
    2
    2
         Lost to follow-up
    123
    133
    Notes
    [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of the 13913 subjects considered for analysis in the trial, 13 were assigned participant codes but did not receive vaccination, hence were excluded from study start.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Zoster-022 GSK1437173A Group
    Reporting group description
    Subjects receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Reporting group title
    Zoster-022 Placebo Group
    Reporting group description
    Subjects receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Reporting group values
    Zoster-022 GSK1437173A Group Zoster-022 Placebo Group Total
    Number of subjects
    6950 6950
    Age categorical
    Units: Subjects
    Age continuous
    Age continuous description
    Units: years
        arithmetic mean (standard deviation)
    75.6 ± 4.7 75.6 ± 4.7 -
    Gender categorical
    Gender categorical description
    Units: Subjects
        Female
    3789 3836 7625
        Male
    3161 3114 6275

    End points

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    End points reporting groups
    Reporting group title
    Zoster-022 GSK1437173A Group
    Reporting group description
    Subjects receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Reporting group title
    Zoster-022 Placebo Group
    Reporting group description
    Subjects receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022 GSK1437173A 70-79YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects between 70 and 79 years of age (YOA), receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022 GSK1437173A >=80YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 80 years of age (YOA), receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022 GSK1437173A >=70YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 70 years of age (YOA), receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022 Placebo 70-79YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects between 70 and 79 years of age (YOA), receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022 Placebo >=80YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 80 years of age (YOA), receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022 Placebo >=70YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 70 years of age (YOA), receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled GSK1437173A 70-79YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects between 70 and 79 years of age (YOA), receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled GSK1437173A >=80YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 80 years of age (YOA), receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled GSK1437173A >=70YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 70 years of age (YOA), receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled Placebo 70-79YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects between 70 and 79 years of age (YOA), receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled Placebo >=80YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 80 years of age (YOA), receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled Placebo >=70YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 70 years of age (YOA), receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled GSK1437173A 50-59 YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects between 50 and 59 years of age (YOA), receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled GSK1437173A 60-69 YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects between 60 and 69 years of age (YOA), receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled GSK1437173A 70-79 YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects between 70 and 79 years of age (YOA), receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled GSK1437173A >=80 YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 80 years of age (YOA), receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled Placebo 50-59 YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects between 50 and 59 years of age (YOA), receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled Placebo 60-69 YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects between 60 and 69 years of age (YOA), receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled Placebo 70-79 YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects between 70 and 79 years of age (YOA), receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled Placebo >=80 YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 80 years of age (YOA), receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled GSK1437173A >=70 YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 70 years of age (YOA), receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Subject analysis set title
    Zoster-022/006 Pooled Placebo >=70 YOA Group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects above 70 years of age (YOA), receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Primary: Number of subjects with any episodes of herpes zoster (HZ)

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    End point title
    Number of subjects with any episodes of herpes zoster (HZ)
    End point description
    Confirmed HZ cases during the study in the modified total vaccinated cohort (mTVc). The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Primary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022 GSK1437173A 70-79YOA Group Zoster-022 GSK1437173A >=80YOA Group Zoster-022 GSK1437173A >=70YOA Group Zoster-022 Placebo 70-79YOA Group Zoster-022 Placebo >=80YOA Group Zoster-022 Placebo >=70YOA Group
    Number of subjects analysed
    5114
    1427
    6541
    5189
    1433
    6622
    Units: Subjects
    17
    6
    23
    169
    54
    223
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of Herpes Zoster (HZ) disease between Zoster-022 GSK1437173A 70-79 YOA group and Zoster-022 Placebo 70-79 YOA group.
    Comparison groups
    Zoster-022 GSK1437173A 70-79YOA Group v Zoster-022 Placebo 70-79YOA Group
    Number of subjects included in analysis
    10303
    Analysis specification
    Pre-specified
    Analysis type
    other [1]
    P-value
    < 0.0001
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    90.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    83.54
         upper limit
    94.32
    Notes
    [1] - The efficacy of Herpes Zoster subunit (HZ/su) vaccine against herpes zoster disease was demonstrated if the lower limit (LL) of the two-sided 95% Confidence Interval (CI) of VE was above 10%.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of Herpes Zoster (HZ) disease between Zoster-022 GSK1437173A >=80YOA Group and Zoster-022 Placebo Zoster-022 Placebo >=80YOA Group
    Comparison groups
    Zoster-022 Placebo >=80YOA Group v Zoster-022 GSK1437173A >=80YOA Group
    Number of subjects included in analysis
    2860
    Analysis specification
    Pre-specified
    Analysis type
    other [2]
    P-value
    < 0.0001
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    89.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    74.65
         upper limit
    96.16
    Notes
    [2] - The efficacy of HZ/su vaccine against herpes zoster disease was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 10%
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of Herpes Zoster (HZ) disease between Zoster-022 GSK1437173A >=70YOA Group and Zoster-022 Placebo >=70YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=70YOA Group v Zoster-022 Placebo >=70YOA Group
    Number of subjects included in analysis
    13163
    Analysis specification
    Pre-specified
    Analysis type
    other [3]
    P-value
    < 0.0001
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    89.79
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    84.29
         upper limit
    93.66
    Notes
    [3] - The efficacy of HZ/su vaccine against herpes zoster disease was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 10%

    Primary: Outcome measure for the pooled analysis of combined data from studies ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229): Number of subjects with post-herpetic neuralgia (PHN)

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    End point title
    Outcome measure for the pooled analysis of combined data from studies ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229): Number of subjects with post-herpetic neuralgia (PHN)
    End point description
    Incidence of PHN calculated using the mTVc during the entire study period in subjects ≥ 70 years of age (YOA). The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Primary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022/006 Pooled GSK1437173A 70-79YOA Group Zoster-022/006 Pooled GSK1437173A >=80YOA Group Zoster-022/006 Pooled GSK1437173A >=70YOA Group Zoster-022/006 Pooled Placebo 70-79YOA Group Zoster-022/006 Pooled Placebo >=80YOA Group Zoster-022/006 Pooled Placebo >=70YOA Group
    Number of subjects analysed
    6468
    1782
    8250
    6554
    1792
    8346
    Units: Subjects
    2
    2
    4
    29
    7
    36
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of Post-Herpetic Neuralgia (PHN) between Zoster-022/006 Pooled GSK1437173A 70-79 YOA Group and Zoster-022/006 Pooled Placebo 70-79YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A 70-79YOA Group v Zoster-022/006 Pooled Placebo 70-79YOA Group
    Number of subjects included in analysis
    13022
    Analysis specification
    Pre-specified
    Analysis type
    other [4]
    P-value
    < 0.0001
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    93.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    72.47
         upper limit
    99.19
    Notes
    [4] - The efficacy of HZ/su vaccine against PHN was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 0%
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of PHN between Zoster-022/006 Pooled GSK1437173A>=80YOA Group and Zoster-022/006 Pooled Placebo >=80YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A >=80YOA Group v Zoster-022/006 Pooled Placebo >=80YOA Group
    Number of subjects included in analysis
    3574
    Analysis specification
    Pre-specified
    Analysis type
    other [5]
    P-value
    = 0.1844
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    71.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -51.51
         upper limit
    97.08
    Notes
    [5] - The efficacy of HZ/su vaccine against PHN was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 0%
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of PHN between Zoster-022/006 Pooled GSK1437173A>=70YOA Group and Zoster-022/006 Pooled Placebo >=70YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A >=70YOA Group v Zoster-022/006 Pooled Placebo >=70YOA Group
    Number of subjects included in analysis
    16596
    Analysis specification
    Pre-specified
    Analysis type
    other [6]
    P-value
    < 0.0001
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    88.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    68.7
         upper limit
    97.1
    Notes
    [6] - The efficacy of HZ/su vaccine against PHN was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 0%

    Primary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with confirmed HZ

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with confirmed HZ
    End point description
    Occurrence of confirmed HZ during the entire study period in subjects ≥ 70 YOA. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Primary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022/006 Pooled GSK1437173A 70-79YOA Group Zoster-022/006 Pooled GSK1437173A >=80YOA Group Zoster-022/006 Pooled GSK1437173A >=70YOA Group Zoster-022/006 Pooled Placebo 70-79YOA Group Zoster-022/006 Pooled Placebo >=80YOA Group Zoster-022/006 Pooled Placebo >=70YOA Group
    Number of subjects analysed
    6468
    1782
    8250
    6554
    1792
    8346
    Units: Subjects
    19
    6
    25
    216
    68
    284
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of herpes zoster disease between Zoster-022/006 Pooled GSK1437173A 70-79YOA Group and Zoster-022/006 Pooled Placebo 70-79YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A 70-79YOA Group v Zoster-022/006 Pooled Placebo 70-79YOA Group
    Number of subjects included in analysis
    13022
    Analysis specification
    Pre-specified
    Analysis type
    other [7]
    P-value
    < 0.0001
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    91.27
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    86.04
         upper limit
    94.85
    Notes
    [7] - The efficacy of HZ/su vaccine against herpes zoster disease was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 10%
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of herpes zoster disease between Zoster-022/006 Pooled GSK1437173A >=80YOA Group and Zoster-022/006 Pooled Placebo >=80YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A >=80YOA Group v Zoster-022/006 Pooled Placebo >=80YOA Group
    Number of subjects included in analysis
    3574
    Analysis specification
    Pre-specified
    Analysis type
    other [8]
    P-value
    < 0.0001
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    91.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    80.22
         upper limit
    96.94
    Notes
    [8] - The efficacy of HZ/su vaccine against herpes zoster disease was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 10%
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of herpes zoster disease between Zoster-022/006 GSK1437173A >=70 YOA Group and Zoster-022/006 Pooled Placebo >=70YOA Group
    Comparison groups
    Zoster-022/006 Pooled Placebo >=70YOA Group v Zoster-022/006 Pooled GSK1437173A >=70YOA Group
    Number of subjects included in analysis
    16596
    Analysis specification
    Pre-specified
    Analysis type
    other [9]
    P-value
    < 0.0001
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    91.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    86.88
         upper limit
    94.46
    Notes
    [9] - The efficacy of HZ/su vaccine against herpes zoster disease was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 10%

    Secondary: Number of subjects with post-herpetic neuralgia (PHN)

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    End point title
    Number of subjects with post-herpetic neuralgia (PHN)
    End point description
    PHN cases in the mTVc. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022 GSK1437173A 70-79YOA Group Zoster-022 GSK1437173A >=80YOA Group Zoster-022 GSK1437173A >=70YOA Group Zoster-022 Placebo 70-79YOA Group Zoster-022 Placebo >=80YOA Group Zoster-022 Placebo >=70YOA Group
    Number of subjects analysed
    5114
    1427
    6541
    5189
    1433
    6622
    Units: Subjects
    2
    2
    4
    22
    6
    28
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of of Vaccine Efficacy (VE) in prevention of PHN between Zoster-022 GSK1437173A 70-79YOA Group and Zoster-022 placebo 70-79YOA Group
    Comparison groups
    Zoster-022 GSK1437173A 70-79YOA Group v Zoster-022 Placebo 70-79YOA Group
    Number of subjects included in analysis
    10303
    Analysis specification
    Pre-specified
    Analysis type
    other [10]
    P-value
    < 0.0001
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    90.8
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    62.57
         upper limit
    98.95
    Notes
    [10] - The efficacy of HZ/su vaccine against PHN was demonstrated if the LL of the two-sided 95% CI of VE was above 0%.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of PHN between Zoster-022 GSK1437173A >=80YOA Group and Zoster-022 Placebo >=80YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=80YOA Group v Zoster-022 Placebo >=80YOA Group
    Number of subjects included in analysis
    2860
    Analysis specification
    Pre-specified
    Analysis type
    other [11]
    P-value
    = 0.3072
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    65.76
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -91.58
         upper limit
    96.62
    Notes
    [11] - The efficacy of HZ/su vaccine against PHN was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 0%
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of PHN between Zoster-022 GSK1437173A >=70YOA Group and Zoster-022 Placebo >=70YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=70YOA Group v Zoster-022 Placebo >=70YOA Group
    Number of subjects included in analysis
    13163
    Analysis specification
    Pre-specified
    Analysis type
    other [12]
    P-value
    < 0.0001
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    85.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    58.52
         upper limit
    96.3
    Notes
    [12] - The efficacy of HZ/su vaccine against PHN was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 0%

    Secondary: Number of days with severe ‘worst’ HZ-associated pain

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    End point title
    Number of days with severe ‘worst’ HZ-associated pain
    End point description
    Duration of severe ‘worst’ HZ-associated pain following the onset of a confirmed HZ rash over the entire pain reporting period as measured by the Zoster Brief Pain Inventory (ZBPI) in subjects with confirmed HZ. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022 GSK1437173A 70-79YOA Group Zoster-022 GSK1437173A >=80YOA Group Zoster-022 GSK1437173A >=70YOA Group Zoster-022 Placebo 70-79YOA Group Zoster-022 Placebo >=80YOA Group Zoster-022 Placebo >=70YOA Group
    Number of subjects analysed
    15
    3
    18
    150
    48
    198
    Units: Days
        arithmetic mean (standard deviation)
    21.8 ± 31.41
    98.7 ± 57.73
    34.6 ± 45.54
    47.9 ± 100.08
    50.4 ± 106.51
    48.5 ± 101.4
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of VE in reduction of duration of severe worst HZ associated pain between Zoster-022 GSK1437173A 70-79YOA Group and Zoster-022 Placebo 70-79YOA Group
    Comparison groups
    Zoster-022 Placebo 70-79YOA Group v Zoster-022 GSK1437173A 70-79YOA Group
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    other [13]
    P-value
    = 0.3749
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    21.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -34.4
         upper limit
    54.39
    Notes
    [13] - The efficacy of HZ/su vaccine against duration of severe worst HZ associated pain was demonstrated if the LL of the two-sided 95% CI of VE derived from the Hazard ratio was above 0%.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of VE in reduction of duration of severe worst HZ associated pain between Zoster-022 GSK1437173A >=80YOA Group and Zoster-022 Placebo>=80YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=80YOA Group v Zoster-022 Placebo >=80YOA Group
    Number of subjects included in analysis
    51
    Analysis specification
    Pre-specified
    Analysis type
    other [14]
    P-value
    = 0.2466
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    51.76
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -65.55
         upper limit
    85.95
    Notes
    [14] - The efficacy of HZ/su vaccine against duration of severe worst HZ associated pain was demonstrated if the LL of the two-sided 95% CI of VE derived from the Hazard ratio was above 0%.
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Comparison of VE in reduction of duration of severe worst HZ associated pain between Zoster-022 GSK1437173A >=70YOA Group and Zoster-022 Placebo>=70YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=70YOA Group v Zoster-022 Placebo >=70YOA Group
    Number of subjects included in analysis
    216
    Analysis specification
    Pre-specified
    Analysis type
    other [15]
    P-value
    = 0.1877
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    28.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    17.69
         upper limit
    56.44
    Notes
    [15] - The efficacy of HZ/su vaccine against duration of severe worst HZ associated pain was demonstrated if the LL of the two-sided 95% CI of VE derived from the Hazard ratio was above 0%.

    Secondary: Number of subjects with confirmed HZ episode related mortality and hospitalizations

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    End point title
    Number of subjects with confirmed HZ episode related mortality and hospitalizations
    End point description
    The number of subjects with confirmed HZ related mortality and hospitalizations were tabulated. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022 GSK1437173A 70-79YOA Group Zoster-022 GSK1437173A >=80YOA Group Zoster-022 GSK1437173A >=70YOA Group Zoster-022 Placebo 70-79YOA Group Zoster-022 Placebo >=80YOA Group Zoster-022 Placebo >=70YOA Group
    Number of subjects analysed
    5114
    1427
    6541
    5189
    1433
    6622
    Units: Subjects
        Mortality
    0
    0
    0
    0
    0
    0
        Hospitalization
    0
    0
    0
    3
    2
    5
        Mortality or hospitalization
    0
    0
    0
    3
    2
    5
    No statistical analyses for this end point

    Secondary: Number of subjects with overall mortality and HZ-related mortality

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    End point title
    Number of subjects with overall mortality and HZ-related mortality
    End point description
    The number of subjects with overall mortality and HZ related mortality were tabulated. Evaluation of VE in the reduction of overall and HZ related mortality as per study objective was not performed due to low number of events reported. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022 GSK1437173A 70-79YOA Group Zoster-022 GSK1437173A >=80YOA Group Zoster-022 GSK1437173A >=70YOA Group Zoster-022 Placebo 70-79YOA Group Zoster-022 Placebo >=80YOA Group Zoster-022 Placebo >=70YOA Group
    Number of subjects analysed
    5114
    1427
    6541
    5189
    1433
    6622
    Units: Subjects
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with confirmed HZ episode related hospitalizations

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    End point title
    Number of subjects with confirmed HZ episode related hospitalizations
    End point description
    Incidence of overall and HZ-related hospitalizations during the study. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022 GSK1437173A 70-79YOA Group Zoster-022 GSK1437173A >=80YOA Group Zoster-022 GSK1437173A >=70YOA Group Zoster-022 Placebo 70-79YOA Group Zoster-022 Placebo >=80YOA Group Zoster-022 Placebo >=70YOA Group
    Number of subjects analysed
    5114
    1427
    6541
    5189
    1433
    6622
    Units: Subjects
    0
    0
    0
    3
    2
    5
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of VE in reduction of overall and HZ related hospitalizations between Zoster-022 GSK1437173A 70-79YOA Group and Zoster-022 Placebo 70-79YOA Group
    Comparison groups
    Zoster-022 GSK1437173A 70-79YOA Group v Zoster-022 Placebo 70-79YOA Group
    Number of subjects included in analysis
    10303
    Analysis specification
    Pre-specified
    Analysis type
    other [16]
    P-value
    = 0.2533
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -144.13
         upper limit
    100
    Notes
    [16] - Efficacy of the HZ/su vaccine against overall and HZ related hospitalizations was demonstrated if the LL of the two-sided 95% CI of VE was above 0%.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of VE in reduction of overall and HZ related hospitalizations between Zoster-022 GSK1437173A >=80YOA Group and Zoster-022 Placebo >=80YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=80YOA Group v Zoster-022 Placebo >=80YOA Group
    Number of subjects included in analysis
    2860
    Analysis specification
    Pre-specified
    Analysis type
    other [17]
    P-value
    = 0.5024
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -435.14
         upper limit
    100
    Notes
    [17] - Efficacy of the HZ/su vaccine against overall and HZ related hospitalizations was demonstrated if the LL of the two-sided 95% CI of VE was above 0%.
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Comparison of VE in reduction of overall and HZ related hospitalizations between Zoster-022 GSK1437173A >=70YOA Group and Zoster-022 Placebo >=70YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=70YOA Group v Zoster-022 Placebo >=70YOA Group
    Number of subjects included in analysis
    13163
    Analysis specification
    Pre-specified
    Analysis type
    other [18]
    P-value
    = 0.0636
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.92
         upper limit
    100
    Notes
    [18] - Efficacy of the HZ/su vaccine against overall and HZ related hospitalizations was demonstrated if the LL of the two-sided 95% CI of VE was above 0%.

    Secondary: Number of subjects with HZ related complications

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    End point title
    Number of subjects with HZ related complications
    End point description
    Incidence of HZ complications during the study in subjects with confirmed HZ. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022 GSK1437173A 70-79YOA Group Zoster-022 GSK1437173A >=80YOA Group Zoster-022 GSK1437173A >=70YOA Group Zoster-022 Placebo 70-79YOA Group Zoster-022 Placebo >=80YOA Group Zoster-022 Placebo >=70YOA Group
    Number of subjects analysed
    17
    6
    23
    169
    54
    223
    Units: Subjects
        At least one complication
    1
    0
    1
    6
    4
    10
        HZ vasculitis
    0
    0
    0
    0
    0
    0
        Disseminated Disease
    0
    0
    0
    0
    2
    2
        Ophthalmic Disease
    1
    0
    1
    4
    2
    6
        Neurologic Disease
    0
    0
    0
    3
    0
    3
        Visceral Disease
    0
    0
    0
    0
    0
    0
        Stroke
    0
    0
    0
    0
    0
    0
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of VE in reduction of HZ related complications between Zoster-022 GSK1437173A 70-79YOA Group and Zoster-022 Placebo 70-79YOA Group
    Comparison groups
    Zoster-022 GSK1437173A 70-79YOA Group v Zoster-022 Placebo 70-79YOA Group
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    other [19]
    P-value
    = 0.4947
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    -65.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -827.06
         upper limit
    73.62
    Notes
    [19] - Efficacy of the HZ/su vaccine against HZ related complications was demonstrated if the LL of the VE was above 0%.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of VE in reduction of HZ related complications between Zoster-022 GSK1437173A >=80YOA Group and Zoster-022 Placebo >=80YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=80YOA Group v Zoster-022 Placebo >=80YOA Group
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    other [20]
    P-value
    = 1
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -558.05
         upper limit
    100
    Notes
    [20] - Efficacy of the HZ/su vaccine against HZ related complications was demonstrated if the LL of the VE was above 0%
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Comparison of VE in reduction of HZ related complications between Zoster-022 GSK1437173A >=70YOA Group and Zoster-022 Placebo >=70YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=70YOA Group v Zoster-022 Placebo >=70YOA Group
    Number of subjects included in analysis
    246
    Analysis specification
    Pre-specified
    Analysis type
    other [21]
    P-value
    = 1
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    0.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -433.32
         upper limit
    83.16
    Notes
    [21] - Efficacy of the HZ/su vaccine against HZ related complications was demonstrated if the LL of the VE was above 0%

    Secondary: Number of subjects receiving pain medication associated with HZ

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    End point title
    Number of subjects receiving pain medication associated with HZ
    End point description
    Incidence of use of pain medications throughout the study. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022 GSK1437173A 70-79YOA Group Zoster-022 GSK1437173A >=80YOA Group Zoster-022 GSK1437173A >=70YOA Group Zoster-022 Placebo 70-79YOA Group Zoster-022 Placebo >=80YOA Group Zoster-022 Placebo >=70YOA Group
    Number of subjects analysed
    17
    6
    23
    169
    54
    223
    Units: Subjects
        At least 1 pain medication
    7
    3
    10
    123
    37
    160
        1 pain medication only
    5
    0
    5
    43
    17
    60
        2 pain medications only
    0
    1
    1
    30
    4
    34
        3 pain medications or more
    2
    2
    4
    50
    16
    66
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of VE in reduction in use of pain medication between Zoster-022 GSK1437173A 70-79YOA Group and Zoster-022 Placebo 70-79YOA Group
    Comparison groups
    Zoster-022 GSK1437173A 70-79YOA Group v Zoster-022 Placebo 70-79YOA Group
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    other [22]
    P-value
    = 0.0112
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    43.42
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.77
         upper limit
    70.53
    Notes
    [22] - Efficacy of the HZ/su vaccine against use of pain medications was demonstrated if the LL of the two-sided 95% CI of VE was above 0%.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of VE in reduction in use of pain medication between Zoster-022 GSK1437173A >=80YOA Group and Zoster-022 Placebo >=80YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=80YOA Group v Zoster-022 Placebo >=80YOA Group
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    other [23]
    P-value
    = 0.3903
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    27.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -26.43
         upper limit
    73.2
    Notes
    [23] - Efficacy of the HZ/su vaccine against use of pain medications was demonstrated if the LL of the two-sided 95% CI of the VE was above 0%
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Comparison of VE in reduction in use of pain medication between Zoster-022 GSK1437173A >=70YOA group and Zoster-022 Placebo >=70YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=70YOA Group v Zoster-022 Placebo >=70YOA Group
    Number of subjects included in analysis
    246
    Analysis specification
    Pre-specified
    Analysis type
    other [24]
    P-value
    = 0.0083
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    39.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.79
         upper limit
    64.75
    Notes
    [24] - Efficacy of the HZ/su vaccine against use of pain medications was demonstrated if the LL of the two-sided 95% CI of VE was above 0%.

    Secondary: Number of days with pain medication associated with HZ

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    End point title
    Number of days with pain medication associated with HZ
    End point description
    Incidence of reduction of duration of pain medication associated with HZ throughout the study. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022 GSK1437173A 70-79YOA Group Zoster-022 GSK1437173A >=80YOA Group Zoster-022 GSK1437173A >=70YOA Group Zoster-022 Placebo 70-79YOA Group Zoster-022 Placebo >=80YOA Group Zoster-022 Placebo >=70YOA Group
    Number of subjects analysed
    7
    3
    10
    123
    37
    160
    Units: Days
        arithmetic mean (standard deviation)
    38.7 ± 56.44
    274.7 ± 337
    109.5 ± 200.88
    218.6 ± 593.8
    135 ± 207.31
    199.3 ± 530.6
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of VE in reduction in duration of pain medication associated with HZ between Zoster-022 GSK1437173A 70-79YOA Group and Zoster-022 Placebo 70-79YOA Group
    Comparison groups
    Zoster-022 GSK1437173A 70-79YOA Group v Zoster-022 Placebo 70-79YOA Group
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    other [25]
    P-value
    = 0.0232
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    58.94
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    11.45
         upper limit
    80.96
    Notes
    [25] - Efficacy of the HZ/su vaccine against duration of pain medication associated with HZ was demonstrated if the LL of the two-sided 95% CI of VE derived from the hazard ratio was above 0%.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of VE in reduction in duration of pain medication associated with HZ between Zoster-022 GSK1437173A >=80YOA Group and Zoster-022 Placebo >=80YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=80YOA Group v Zoster-022 Placebo >=80YOA Group
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    other [26]
    P-value
    = 0.8324
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    -14.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -303.3
         upper limit
    67.46
    Notes
    [26] - Efficacy of the HZ/su vaccine against duration of pain medication associated with HZ was demonstrated if the LL of the two-sided 95% CI of VE derived from the hazard ratio was above 0%.
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Comparison of VE in reduction in duration of pain medication associated with HZ between Zoster-022 GSK1437173A >=70YOA Group and Zoster-022 Placebo >=70YOA Group
    Comparison groups
    Zoster-022 GSK1437173A >=70YOA Group v Zoster-022 Placebo >=70YOA Group
    Number of subjects included in analysis
    170
    Analysis specification
    Pre-specified
    Analysis type
    other [27]
    P-value
    = 0.0404
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    49.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.92
         upper limit
    73.47
    Notes
    [27] - Efficacy of the HZ/su vaccine against duration of pain medication associated with HZ was demonstrated if the LL of the two-sided 95% CI of VE derived from the hazard ratio was above 0%.

    Secondary: Number of subjects with any and grade 3 solicited local symptoms

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    End point title
    Number of subjects with any and grade 3 solicited local symptoms
    End point description
    Occurrence, intensity of each solicited local symptom within 7 days (Days 0-6) after each vaccination, in subjects included in the 7-day diary card subset; Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. The analysis was performed on the total vaccinated cohort – Diary Card, which was a subset of subjects from the total vaccinated cohort, who completed diary cards with any solicited symptoms during the 7 days (Day 0 to Day 6) post vaccination period
    End point type
    Secondary
    End point timeframe
    Within the 7 days (Days 0-6) after each vaccination
    End point values
    Zoster-022 GSK1437173A Group Zoster-022 Placebo Group
    Number of subjects analysed
    505
    505
    Units: Subjects
        Any Pain, Dose 1 (N=502;504)
    297
    26
        Grade 3 Pain, Dose 1 (N=502;504)
    12
    1
        Any Redness, Dose 1 (N=502;504)
    143
    3
        Grade 3 Redness, Dose 1 (N=502;504)
    9
    0
        Any Swelling, Dose 1 (N=502;504)
    85
    2
        Grade 3 Swelling, Dose 1 (N=502;504)
    2
    0
        Any Pain, Dose 2 (N=492;491)
    282
    23
        Grade 3 Pain, Dose 2 (N=492;491)
    12
    0
        Any Redness, Dose 2 (N=492;491)
    137
    3
        Grade 3 Redness, Dose 2 (N=492;491)
    15
    0
        Any Swelling, Dose 2 (N=492;491)
    68
    0
        Grade 3 Swelling, Dose 2 (N=492;491)
    7
    0
        Any Pain, Across Doses (N=505;505)
    347
    43
        Grade 3 Pain, Across Doses (N=505;505)
    22
    1
        Any Redness, Across Doses (N=505;505)
    198
    5
        Grade 3 Redness, Across Doses (N=505;505)
    20
    0
        Any Swelling, Across Doses (N=505;505)
    114
    2
        Grade 3 Swelling, Across Doses (N=505;505)
    8
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with any, grade 3 and related solicited general symptoms

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    End point title
    Number of subjects with any, grade 3 and related solicited general symptoms
    End point description
    Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache, myalgia, shivering and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.The analysis was performed on the total vaccinated cohort – Diary Card, which was a subset of subjects from the total vaccinated cohort, who completed diary cards with any solicited symptoms during the 7 days (Day 0 to Day 6) post vaccination period
    End point type
    Secondary
    End point timeframe
    Within the 7 days (Days 0-6) post-vaccination period following each dose and across doses
    End point values
    Zoster-022 GSK1437173A Group Zoster-022 Placebo Group
    Number of subjects analysed
    501
    505
    Units: Subjects
        Any Fatigue, Dose 1 (N=501;503)
    104
    56
        Grade 3 Fatigue, Dose 1 (N=501;503)
    8
    4
        Related Fatigue, Dose 1 (N=501;503)
    85
    34
        Any Gastrointestinal, Dose 1 (N=501;503)
    25
    28
        Grade 3 Gastrointestinal, Dose 1 (N=501;503)
    3
    2
        Related Gastrointestinal, Dose 1 (N=501;503)
    16
    14
        Any Headache, Dose 1 (N=501;503)
    72
    42
        Grade 3 Headache, Dose 1 (N=501;503)
    2
    4
        Related Headache, Dose 1 (N=501;503)
    58
    27
        Any Myalgia, Dose 1 (N=501;503)
    106
    27
        Grade 3 Myalgia, Dose 1 (N=501;503)
    6
    2
        Related Myalgia, Dose 1 (N=501;503)
    91
    16
        Any Shivering, Dose 1 (N=501;503)
    38
    17
        Grade 3 Shivering, Dose 1 (N=501;503)
    1
    1
        Related Shivering, Dose 1 (N=501;503)
    32
    12
        Any Temperature, Dose 1 (N=501;503)
    39
    9
        Grade 3 Temperature, Dose 1 (N=501;503)
    0
    2
        Related Temperature, Dose 1 (N=501;503)
    31
    4
        Any Fatigue, Dose 2 (N=492;489)
    122
    39
        Grade 3 Fatigue, Dose 2 (N=492;489)
    9
    0
        Related Fatigue, Dose 2 (N=492;489)
    105
    30
        Any Gastrointestinal, Dose 2 (N=492;489)
    37
    19
        Grade 3 Gastrointestinal, Dose 2 (N=492;489)
    3
    1
        Related Gastrointestinal, Dose 2 (N=492;489)
    26
    13
        Any Headache, Dose 2 (N=492;489)
    76
    26
        Grade 3 Headache, Dose 2 (N=492;489)
    4
    0
        Related Headache, Dose 2 (N=492;489)
    63
    20
        Any Myalgia, Dose 2 (N=492;489)
    113
    18
        Grade 3 Myalgia, Dose 2 (N=492;489)
    7
    0
        Related Myalgia, Dose 2 (N=492;489)
    94
    16
        Any Shivering, Dose 2 (N=492;489)
    59
    11
        Grade 3 Shivering, Dose 2 (N=492;489)
    5
    1
        Related Shivering, Dose 2 (N=492;489)
    47
    9
        Any Temperature, Dose 2 (N=492;489)
    38
    6
        Grade 3 Temperature, Dose 2 (N=492;489)
    0
    2
        Related Temperature, Dose 2 (N=492;489)
    35
    2
        Any Fatigue, Across Doses (N=504;505)
    166
    77
        Grade 3 Fatigue, Across Doses (N=504;505)
    16
    4
        Related Fatigue, Across Doses (N=504;505)
    140
    52
        Any Gastrointestinal, Across Doses (N=504;505)
    55
    40
        Grade 3 Gastrointestinal, Across Doses (N=504;505)
    5
    2
        Related Gastrointestinal, Across Doses (N=504;505)
    38
    21
        Any Headache, Across Doses (N=504;505)
    124
    55
        Grade 3 Headache, Across Doses (N=504;505)
    5
    4
        Related Headache, Across Doses (N=504;505)
    104
    37
        Any Myalgia, Across Doses (N=504;505)
    157
    41
        Grade 3 Myalgia, Across Doses (N=504;505)
    12
    2
        Related Myalgia, Across Doses (N=504;505)
    137
    29
        Any Shivering, Across Doses (N=504;505)
    75
    22
        Grade 3 Shivering, Across Doses (N=504;505)
    6
    2
        Related Shivering, Across Doses (N=504;505)
    64
    16
        Any Temperature, Across Doses (N=504;505)
    62
    13
        Grade 3 Temperature, Across Doses (N=504;505)
    0
    2
        Related Temperature, Across Doses (N=504;505)
    54
    6
    No statistical analyses for this end point

    Secondary: Number of subjects with any, grade 3 and related unsolicited adverse events (AEs)

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    End point title
    Number of subjects with any, grade 3 and related unsolicited adverse events (AEs)
    End point description
    Occurrence, intensity and relationship to vaccination of unsolicited AEs during 30 days (Days 0-29) after each vaccination, according to the Medical Dictionary for Regulatory Activities (MedDRA) classification in all subjects. An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
    End point type
    Secondary
    End point timeframe
    Within the 30 days (Days 0-29) after each vaccination
    End point values
    Zoster-022 GSK1437173A Group Zoster-022 Placebo Group
    Number of subjects analysed
    6950
    6950
    Units: Subjects
        Any AE(s)
    3859
    2263
        Grade 3 AE(s)
    485
    265
        Related AE(s)
    2853
    529
    No statistical analyses for this end point

    Secondary: Number of subjects with any and related serious adverse events (SAEs)

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    End point title
    Number of subjects with any and related serious adverse events (SAEs)
    End point description
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
    End point type
    Secondary
    End point timeframe
    From Month 0 to Month 14
    End point values
    Zoster-022 GSK1437173A Group Zoster-022 Placebo Group
    Number of subjects analysed
    6950
    6950
    Units: Subjects
        Any SAE(s)
    891
    939
        Related SAE(s)
    12
    7
    No statistical analyses for this end point

    Secondary: Number of subjects with any and related potential immune mediated diseases (pIMDs)

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    End point title
    Number of subjects with any and related potential immune mediated diseases (pIMDs)
    End point description
    Occurrence and relationship to vaccination of any potential immune-mediated diseases (pIMDs) during the entire study period in all subjects. This analysis was based on the the total vaccinated cohort, which included all subjects with at least one dose of study vaccine or placebo administered.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022 GSK1437173A Group Zoster-022 Placebo Group
    Number of subjects analysed
    6950
    6950
    Units: Subjects
        Any pIMD
    92
    97
        Related pIMD(s)
    8
    6
    No statistical analyses for this end point

    Secondary: Number of subjects with any and related Medically Attended visits

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    End point title
    Number of subjects with any and related Medically Attended visits
    End point description
    Occurrence and relationship to vaccination of medically attended visits other than routine health care visits, from Month 0 to Month 8 in all subjects. Medically attended visits were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any medically attended visits(s) = Occurrence of any medically attended visits(s) regardless of intensity grade or relation to vaccination. This analysis was based on the the total vaccinated cohort, which included all subjects with at least one dose of study vaccine or placebo administered.
    End point type
    Secondary
    End point timeframe
    From Month 0 to Month 8 post-vaccination
    End point values
    Zoster-022 GSK1437173A Group Zoster-022 Placebo Group
    Number of subjects analysed
    6950
    6950
    Units: Subjects
        Any medically attended visits
    2882
    2911
        Related medically attended visits
    165
    66
    No statistical analyses for this end point

    Secondary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Overall number of subjects with PHN in subjects ≥ 50 YOA

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Overall number of subjects with PHN in subjects ≥ 50 YOA
    End point description
    Incidence of PHN calculated using the mTVc during the entire study period in subjects ≥ 50 YOA. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022/006 Pooled GSK1437173A 50-59 YOA Group Zoster-022/006 Pooled GSK1437173A 60-69 YOA Group Zoster-022/006 Pooled GSK1437173A 70-79 YOA Group Zoster-022/006 Pooled GSK1437173A >=80 YOA Group Zoster-022/006 Pooled Placebo 50-59 YOA Group Zoster-022/006 Pooled Placebo 60-69 YOA Group Zoster-022/006 Pooled Placebo 70-79 YOA Group Zoster-022/006 Pooled Placebo >=80 YOA Group
    Number of subjects analysed
    3491
    2140
    6468
    1782
    3523
    2166
    6554
    1792
    Units: Subjects
    0
    0
    2
    2
    8
    2
    29
    7
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of PHN between Zoster-022/006 Pooled GSK1437173A 50-59YOA Group and Zoster-022/006 Pooled Placebo 50-59YOA Group.Comparison of vaccine efficacy for groups 70-79 and above 80 YOA are presented in outcome measure 2.
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A 50-59 YOA Group v Zoster-022/006 Pooled Placebo 50-59 YOA Group
    Number of subjects included in analysis
    7014
    Analysis specification
    Pre-specified
    Analysis type
    other [28]
    P-value
    = 0.0081
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    40.88
         upper limit
    100
    Notes
    [28] - The efficacy of HZ/su vaccine against PHN was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 0%
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of vaccine efficacy in prevention of PHN between Zoster-022/006 Pooled GSK1437173A 60-69YOA Group and Zoster-022/006 Pooled Placebo 60-69YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A 60-69 YOA Group v Zoster-022/006 Pooled Placebo 60-69 YOA Group
    Number of subjects included in analysis
    4306
    Analysis specification
    Pre-specified
    Analysis type
    other [29]
    P-value
    = 0.5097
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -442.83
         upper limit
    100
    Notes
    [29] - The efficacy of HZ/su vaccine against PHN was demonstrated if the lower limit of the of the 2-sided 95% CI of VE was above 0%

    Secondary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with a reduction of PHN incidence in subjects ≥ 50 YOA with confirmed HZ

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with a reduction of PHN incidence in subjects ≥ 50 YOA with confirmed HZ
    End point description
    Occurrence of PHN during the entire study period in all subjects with confirmed HZ.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022/006 Pooled GSK1437173A 50-59 YOA Group Zoster-022/006 Pooled GSK1437173A 60-69 YOA Group Zoster-022/006 Pooled GSK1437173A 70-79 YOA Group Zoster-022/006 Pooled GSK1437173A >=80 YOA Group Zoster-022/006 Pooled Placebo 50-59 YOA Group Zoster-022/006 Pooled Placebo 60-69 YOA Group Zoster-022/006 Pooled Placebo 70-79 YOA Group Zoster-022/006 Pooled Placebo >=80 YOA Group
    Number of subjects analysed
    4
    3
    19
    6
    103
    90
    216
    68
    Units: Subjects
    0
    0
    2
    2
    8
    2
    29
    7
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of Vaccine efficacy in reduction of PHN incidence in subjects with confirmed HZ episode in Zoster-022/006 Pooled GSK1437173A 50-59 YOA Group versus Zoster-022/006 Pooled Placebo 50-59 YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A 50-59 YOA Group v Zoster-022/006 Pooled Placebo 50-59 YOA Group
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    other [30]
    P-value
    = 1
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -649.86
         upper limit
    100
    Notes
    [30] - The efficacy of HZ/su vaccine in reduction of PHN in subjects with confirmed HZ episodes was demonstrated if the LL of the two-sided 95% CI of VE was above 0%
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of Vaccine efficacy in reduction of PHN incidence in subjects with confirmed HZ episode in Zoster-022/006 Pooled GSK1437173A 60-69 YOA Group versus Zoster-022/006 Pooled Placebo 60-69 YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A 60-69 YOA Group v Zoster-022/006 Pooled Placebo 60-69 YOA Group
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    other [31]
    P-value
    = 1
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    100
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3938.7
         upper limit
    100
    Notes
    [31] - The efficacy of HZ/su vaccine in reduction of PHN in subjects with confirmed HZ episodes was demonstrated if the LL of the two-sided 95% CI of VE was above 0%
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Comparison of Vaccine efficacy in reduction of PHN incidence in subjects with confirmed HZ episode in Zoster-022/006 Pooled GSK1437173A 70-79 YOA Group versus Zoster-022/006 Pooled Placebo 70-79 YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A 70-79 YOA Group v Zoster-022/006 Pooled Placebo 70-79 YOA Group
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    other [32]
    P-value
    = 1
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    21.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -149.41
         upper limit
    78.91
    Notes
    [32] - The efficacy of HZ/su vaccine in reduction of PHN in subjects with confirmed HZ episodes was demonstrated if the LL of the two-sided 95% CI of VE was above 0%
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    Comparison of Vaccine efficacy in reduction of PHN incidence in subjects with confirmed HZ episode in Zoster-022/006 Pooled GSK1437173A >=80 YOA Group versus Zoster-022/006 Pooled Placebo>=80 YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A >=80 YOA Group v Zoster-022/006 Pooled Placebo >=80 YOA Group
    Number of subjects included in analysis
    74
    Analysis specification
    Pre-specified
    Analysis type
    other [33]
    P-value
    = 0.1528
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    -223.81
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -883.05
         upper limit
    18.84
    Notes
    [33] - The efficacy of HZ/su vaccine in reduction of PHN in subjects with confirmed HZ episodes was demonstrated if the LL of the two-sided 95% CI of VE was above 0%

    Secondary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with reduction of duration of severe ‘worst’ HZ-associated pain in subjects ≥ 70 YOA with confirmed HZ

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with reduction of duration of severe ‘worst’ HZ-associated pain in subjects ≥ 70 YOA with confirmed HZ
    End point description
    The duration of severe ‘worst’ HZ-associated pain following the onset of a confirmed HZ rash over the entire pain reporting period was measured by the ZBPI in subjects ≥ 70 YOA with confirmed HZ. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022/006 Pooled GSK1437173A 70-79 YOA Group Zoster-022/006 Pooled GSK1437173A >=80 YOA Group Zoster-022/006 Pooled Placebo 70-79 YOA Group Zoster-022/006 Pooled Placebo >=80 YOA Group Zoster-022/006 Pooled GSK1437173A >=70 YOA Group Zoster-022/006 Pooled Placebo >=70 YOA Group
    Number of subjects analysed
    19
    6
    216
    68
    25
    284
    Units: Subjects
    17
    3
    193
    61
    20
    254
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Comparison of VE in reduction of duration of severe worst HZ associated pain between Zoster-022/006 pooled GSK1437173A 70-79YOA Group and Zoster-022/006 pooled Placebo 70-79YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A 70-79 YOA Group v Zoster-022/006 Pooled Placebo 70-79 YOA Group
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    other [34]
    P-value
    = 0.2885
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    23.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -25.8
         upper limit
    53.78
    Notes
    [34] - The VE of HZ/su against duration of severe worst pain in subjects with confirmed HZ was demonstrated if the LL of the two-sided 95% CI of VE derived from the Hazard ratio was above 0%.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Comparison of VE in reduction of duration of severe worst HZ associated pain between Zoster-022/006 pooled GSK1437173A >=80 YOA Group and Zoster-022/006 pooled Placebo >=80 YOA Group
    Comparison groups
    Zoster-022/006 Pooled GSK1437173A >=80 YOA Group v Zoster-022/006 Pooled Placebo >=80 YOA Group
    Number of subjects included in analysis
    74
    Analysis specification
    Pre-specified
    Analysis type
    other [35]
    P-value
    = 0.194
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    54.93
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -50.03
         upper limit
    86.46
    Notes
    [35] - The VE of HZ/su against duration of severe worst pain in subjects with confirmed HZ was demonstrated if the LL of the two-sided 95% CI of VE derived from the Hazard ratio was above 0%.
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Comparison of VE in reduction of duration of severe worst HZ associated pain between Zoster-022/006 pooled GSK1437173A >=70 YOA Group and Zoster-022/006 pooled Placebo>=70 YOA Group
    Comparison groups
    Zoster-022/006 Pooled Placebo >=70 YOA Group v Zoster-022/006 Pooled GSK1437173A >=70 YOA Group
    Number of subjects included in analysis
    309
    Analysis specification
    Pre-specified
    Analysis type
    other [36]
    P-value
    = 0.1243
    Method
    Poisson exact test
    Parameter type
    Vaccine efficacy
    Point estimate
    30.48
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.52
         upper limit
    56.27
    Notes
    [36] - The VE of HZ/su against duration of severe worst pain in subjects with confirmed HZ was demonstrated if the LL of the two-sided 95% CI of VE derived from the Hazard ratio was above 0%.

    Secondary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Duration of severe ‘worst’ HZ-associated pain in subjects ≥ 70 YOA with confirmed HZ

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Duration of severe ‘worst’ HZ-associated pain in subjects ≥ 70 YOA with confirmed HZ
    End point description
    Duration of severe ‘worst’ HZ-associated pain following the onset of a confirmed HZ rash over the entire pain reporting period was measured by the ZBPI in subjects ≥ 70 YOA with confirmed HZ. The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022/006 Pooled GSK1437173A 70-79 YOA Group Zoster-022/006 Pooled GSK1437173A >=80 YOA Group Zoster-022/006 Pooled Placebo 70-79 YOA Group Zoster-022/006 Pooled Placebo >=80 YOA Group Zoster-022/006 Pooled GSK1437173A >=70 YOA Group Zoster-022/006 Pooled Placebo >=70 YOA Group
    Number of subjects analysed
    17
    3
    193
    61
    20
    254
    Units: Days
        arithmetic mean (standard deviation)
    20.3 ± 29.71
    98.7 ± 57.73
    48.3 ± 96.34
    45.2 ± 95.58
    32.1 ± 43.80
    47.5 ± 95.98
    No statistical analyses for this end point

    Secondary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any and Grade 3 solicited local symptoms

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any and Grade 3 solicited local symptoms
    End point description
    Occurrence, intensity of each solicited local symptom within 7 days (Days 0-6) after each vaccination, in subjects ≥ 70 YOA. Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. The analysis was performed on the total vaccinated cohort – Diary Card, which was a subset of subjects from the total vaccinated cohort, who completed diary cards with any solicited symptoms during the 7 days (Day 0 to Day 6) post vaccination period.
    End point type
    Secondary
    End point timeframe
    Within 7 days (Days 0-6) post-vaccination period following each dose and across doses
    End point values
    Zoster-022/006 Pooled GSK1437173A >=70 YOA Group Zoster-022/006 Pooled Placebo >=70 YOA Group
    Number of subjects analysed
    2258
    2263
    Units: Subjects
        Any Pain, Dose 1 (N=2246;2255)
    1336
    128
        Grade 3 Pain, Dose 1 (N=2246;2255)
    42
    1
        Any Redness, Dose 1 (N=2246;2255)
    606
    17
        Grade 3 Redness, Dose 1 (N=2246;2255)
    43
    0
        Any Swelling, Dose 1 (N=2246;2255)
    355
    17
        Grade 3 Swelling, Dose 1 (N=2246;2255)
    17
    0
        Any Pain, Dose 2 (N=2160;2169)
    1241
    107
        Grade 3 Pain, Dose 2 (N=2160;2169)
    60
    3
        Any Redness, Dose 2 (N=2160;2169)
    582
    14
        Grade 3 Redness, Dose 2 (N=2160;2169)
    39
    0
        Any Swelling, Dose 2 (N=2160;2169)
    344
    10
        Grade 3 Swelling, Dose 2 (N=2160;2169)
    15
    0
        Any Pain, Across Doses (N=2258;2263)
    1562
    199
        Grade 3 Pain, Across Doses (N=2258;2263)
    90
    4
        Any Redness, Across Doses (N=2258;2263)
    851
    27
        Grade 3 Redness, Across Doses (N=2258;2263)
    70
    0
        Any Swelling, Across Doses (N=2258;2263)
    519
    25
        Grade 3 Swelling, Across Doses (N=2258;2263)
    30
    0
    No statistical analyses for this end point

    Secondary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any, Grade 3 and related solicited general symptoms

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any, Grade 3 and related solicited general symptoms
    End point description
    Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache, myalgia, shivering and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. The analysis was performed on the total vaccinated cohort – Diary Card, which was a subset of subjects from the total vaccinated cohort, who completed diary cards with any solicited symptoms during the 7 days (Day 0 to Day 6) post vaccination period.
    End point type
    Secondary
    End point timeframe
    Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses
    End point values
    Zoster-022/006 Pooled GSK1437173A >=70 YOA Group Zoster-022/006 Pooled Placebo >=70 YOA Group
    Number of subjects analysed
    2252
    2264
    Units: Subjects
        Any Fatigue, Dose 1 (N=2237;2256)
    545
    231
        Grade 3 Fatigue, Dose 1 (N=2237;2256)
    31
    13
        Related Fatigue, Dose 1 (N=2237;2256)
    441
    147
        Any Gastrointestinal, Dose 1 (N=2237;2256)
    170
    123
        Grade 3 Gastrointestinal, Dose 1 (N=2237;2256)
    15
    6
        Related Gastrointestinal, Dose 1 (N=2237;2256)
    101
    67
        Any Headache, Dose 1 (N=2237;2256)
    380
    189
        Grade 3 Headache, Dose 1 (N=2237;2256)
    7
    8
        Related Headache, Dose 1 (N=2237;2256)
    293
    132
        Any Myalgia, Dose 1 (N=2237;2256)
    530
    159
        Grade 3 Myalgia, Dose 1 (N=2237;2256)
    26
    7
        Related Myalgia, Dose 1 (N=2237;2256)
    445
    101
        Any Shivering, Dose 1 (N=2237;2256)
    206
    73
        Grade 3 Shivering, Dose 1 (N=2237;2256)
    15
    3
        Related Shivering, Dose 1 (N=2237;2256)
    173
    50
        Any Temperature, Dose 1 (N=2237;2256)
    142
    34
        Grade 3 Temperature, Dose 1 (N=2237;2256)
    1
    2
        Related Temperature, Dose 1 (N=2237;2256)
    111
    16
        Any Fatigue, Dose 2 (N=2159;2166)
    579
    169
        Grade 3 Fatigue, Dose 2 (N=2159;2166)
    53
    4
        Related Fatigue, Dose 2 (N=2159;2166)
    495
    116
        Any Gastrointestinal, Dose 2 (N=2159;2166)
    188
    75
        Grade 3 Gastrointestinal, Dose 2 (N=2159;2166)
    14
    5
        Related Gastrointestinal, Dose 2 (N=2159;2166)
    142
    35
        Any Headache, Dose 2 (N=2159;2166)
    455
    133
        Grade 3 Headache, Dose 2 (N=2159;2166)
    30
    2
        Related Headache, Dose 2 (N=2159;2166)
    386
    86
        Any Myalgia, Dose 2 (N=2159;2166)
    560
    112
        Grade 3 Myalgia, Dose 2 (N=2159;2166)
    42
    4
        Related Myalgia, Dose 2 (N=2159;2166)
    484
    75
        Any Shivering, Dose 2 (N=2159;2166)
    334
    55
        Grade 3 Shivering, Dose 2 (N=2159;2166)
    36
    4
        Related Shivering, Dose 2 (N=2159;2166)
    292
    34
        Any Temperature, Dose 2 (N=2159;2166)
    224
    30
        Grade 3 Temperature, Dose 2 (N=2159;2166)
    2
    3
        Related Temperature, Dose 2 (N=2159;2166)
    189
    14
        Any Fatigue, Across Doses (N=2252;2264)
    825
    326
        Grade 3 Fatigue, Across Doses (N=2252;2264)
    79
    17
        Related Fatigue, Across Doses (N=2252;2264)
    699
    220
        Any Gastrointestinal, Across Doses (N=2252;2264)
    304
    172
        Grade 3 Gastrointestinal,Across Doses(N=2252;2264)
    26
    10
        Related Gastrointestinal,Across Doses(N=2252;2264)
    210
    91
        Any Headache, Across Doses (N=2252;2264)
    653
    268
        Grade 3 Headache, Across Doses (N=2252;2264)
    34
    10
        Related Headache, Across Doses (N=2252;2264)
    547
    185
        Any Myalgia, Across Doses (N=2252;2264)
    790
    225
        Grade 3 Myalgia, Across Doses (N=2252;2264)
    62
    10
        Related Myalgia, Across Doses (N=2252;2264)
    689
    157
        Any Shivering, Across Doses (N=2252;2264)
    439
    110
        Grade 3 Shivering, Across Doses (N=2252;2264)
    49
    6
        Related Shivering, Across Doses (N=2252;2264)
    380
    75
        Any Temperature, Across Doses (N=2252;2264)
    323
    61
        Grade 3 Temperature, Across Doses (N=2252;2264)
    3
    3
        Related Temperature, Across Doses (N=2252;2264)
    265
    30
    No statistical analyses for this end point

    Secondary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any, grade 3 and related unsolicited AEs in subjects ≥ 70 YOA

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any, grade 3 and related unsolicited AEs in subjects ≥ 70 YOA
    End point description
    Occurrence, intensity and relationship to vaccination of unsolicited AEs during 30 days (Days 0-29) after each vaccination, according to the MedDRA classification, in subjects ≥ 70 YOA.An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
    End point type
    Secondary
    End point timeframe
    Within 30 days (Days 0 - 29) after each vaccination
    End point values
    Zoster-022/006 Pooled GSK1437173A >=70 YOA Group Zoster-022/006 Pooled Placebo >=70 YOA Group
    Number of subjects analysed
    8758
    8773
    Units: Subjects
        Any AE(s)
    4366
    2732
        Grade 3 AE(s)
    553
    335
        Related AE(s)
    2961
    578
    No statistical analyses for this end point

    Secondary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any and related SAE

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any and related SAE
    End point description
    Occurrence and relationship to vaccination of all SAEs from Month 0 to Month 14 in subjects ≥ 70 YOA. Related SAEs also included any SAEs related to study participation or concurrent GSK medication/vaccine.
    End point type
    Secondary
    End point timeframe
    From Month 0 to Month 14
    End point values
    Zoster-022/006 Pooled GSK1437173A >=70 YOA Group Zoster-022/006 Pooled Placebo >=70 YOA Group
    Number of subjects analysed
    8758
    8773
    Units: Subjects
        Any SAEs up to Mont 14
    1117
    1171
        Related SAEs up to Month 14
    12
    7
    No statistical analyses for this end point

    Secondary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any and related pIMDs

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any and related pIMDs
    End point description
    Occurrence and relationship to vaccination of any pIMDs during the entire study period in subjects ≥ 70 YOA. The analysis was based on the total vaccinated cohort, which included all vaccinated subjects with study vaccine or placebo administered.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022/006 Pooled GSK1437173A >=70 YOA Group Zoster-022/006 Pooled Placebo >=70 YOA Group
    Number of subjects analysed
    8758
    8773
    Units: Subjects
        Any pIMD(s)
    110
    118
        Related pIMD(s)
    8
    8
    No statistical analyses for this end point

    Secondary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any and related medically attended visits

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with any and related medically attended visits
    End point description
    Occurrence and relationship to vaccination of medically attended visits (defined as hospitalizations, emergency room visits or visits to or from medical personnel), other than routine health care visits, from Month 0 to Month 8 in subjects ≥ 70 YOA.
    End point type
    Secondary
    End point timeframe
    From Month 0 to Month 8 post-vaccination
    End point values
    Zoster-022/006 Pooled GSK1437173A >=70 YOA Group Zoster-022/006 Pooled Placebo >=70 YOA Group
    Number of subjects analysed
    8758
    8773
    Units: Subjects
        Any MAE(s)
    3593
    3648
        Related MAE(s)
    180
    80
    No statistical analyses for this end point

    Secondary: Number of subjects with fatal serious adverse events (SAEs)

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    End point title
    Number of subjects with fatal serious adverse events (SAEs)
    End point description
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. This analysis was based on the the total vaccinated cohort, which included all subjects with at least one dose of study vaccine or placebo administered.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022 GSK1437173A Group Zoster-022 Placebo Group
    Number of subjects analysed
    6950
    6950
    Units: Participants
        Fatal SAE(s)
    426
    459
    No statistical analyses for this end point

    Secondary: Number of subjects with SAEs related to study participation or concomitant GSK medication

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    End point title
    Number of subjects with SAEs related to study participation or concomitant GSK medication
    End point description
    The number of subjects with SAEs related to study participation or concomitant GSK medication were tabulated. The analysis was based on the total vaccinated cohort, which included all subjects with at least one dose of study vaccine or placebo administered.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following day 0)
    End point values
    Zoster-022 GSK1437173A Group Zoster-022 Placebo Group
    Number of subjects analysed
    6950
    6950
    Units: Participants
    57
    84
    No statistical analyses for this end point

    Secondary: Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with fatal SAEs

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    End point title
    Outcome measure for the pooled analysis of combined data from studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of subjects with fatal SAEs
    End point description
    Fatal SAEs during the entire study period in subjects ≥ 70 YOA. The analysis was based on the total vaccinated cohort, which included all vaccinated subjects with study vaccine or placebo administered.
    End point type
    Secondary
    End point timeframe
    During the entire study period (3 to 5 year period following Day 0)
    End point values
    Zoster-022/006 Pooled GSK1437173A >=70 YOA Group Zoster-022/006 Pooled Placebo >=70 YOA Group
    Number of subjects analysed
    8758
    8773
    Units: Subjects
    128
    144
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited symptoms: Within 7 (Days 0-6) days after vaccination; Unsolicited adverse events: within 30 days (Days 0-29) after vaccination; Serious adverse events: during the entire study period (3 to 5 year period following Day 0)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    10.0
    Reporting groups
    Reporting group title
    Zoster-022 Placebo Group
    Reporting group description
    Subjects receiving saline solution (NaCl solution) as control according to a 0, 2-month schedule.

    Reporting group title
    Zoster-022 GSK1437173A Group
    Reporting group description
    Subjects receiving herpes zoster subunit vaccine (gE/AS01B vaccine) according to a 0, 2-month schedule.

    Serious adverse events
    Zoster-022 Placebo Group Zoster-022 GSK1437173A Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1214 / 6950 (17.47%)
    1153 / 6950 (16.59%)
         number of deaths (all causes)
    459
    426
         number of deaths resulting from adverse events
    0
    1
    Vascular disorders
    Aneurysm
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aneurysm ruptured
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Aortic aneurysm
         subjects affected / exposed
    2 / 6950 (0.03%)
    6 / 6950 (0.09%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Aortic aneurysm rupture
         subjects affected / exposed
    4 / 6950 (0.06%)
    4 / 6950 (0.06%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    0 / 4
    Aortic arteriosclerosis
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Aortic occlusion
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Aortic rupture
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    8 / 6950 (0.12%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    5 / 6950 (0.07%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Arteriovenous fistula
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure inadequately controlled
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    3 / 6950 (0.04%)
    5 / 6950 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 3
    0 / 4
    Deep vein thrombosis
         subjects affected / exposed
    9 / 6950 (0.13%)
    6 / 6950 (0.09%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Embolism
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Femoral artery aneurysm
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral artery occlusion
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    6 / 6950 (0.09%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Haemorrhage
         subjects affected / exposed
    3 / 6950 (0.04%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Hypertension
         subjects affected / exposed
    25 / 6950 (0.36%)
    22 / 6950 (0.32%)
         occurrences causally related to treatment / all
    0 / 25
    0 / 22
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Hypertensive crisis
         subjects affected / exposed
    6 / 6950 (0.09%)
    7 / 6950 (0.10%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (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 / 6950 (0.07%)
    6 / 6950 (0.09%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Inferior vena caval occlusion
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Internal haemorrhage
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Labile hypertension
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Microscopic polyangiitis
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrosis ischaemic
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    4 / 6950 (0.06%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    6 / 6950 (0.09%)
    6 / 6950 (0.09%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral vascular disorder
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Temporal arteritis
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thromboangiitis obliterans
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vasculitis
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Venous thrombosis
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Hospitalisation
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal polypectomy
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acral lentiginous melanoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute monocytic leukaemia
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Adenocarcinoma
         subjects affected / exposed
    3 / 6950 (0.04%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Adenocarcinoma gastric
         subjects affected / exposed
    1 / 6950 (0.01%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Adenocarcinoma of colon
         subjects affected / exposed
    4 / 6950 (0.06%)
    4 / 6950 (0.06%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Adenocarcinoma pancreas
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Adrenal adenoma
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adrenal gland cancer
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaplastic astrocytoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Anaplastic thyroid cancer
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    B precursor type acute leukaemia
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    B-cell lymphoma
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    3 / 6950 (0.04%)
    5 / 6950 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign neoplasm of thyroid gland
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign ovarian tumour
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct cancer
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Bladder cancer
         subjects affected / exposed
    13 / 6950 (0.19%)
    6 / 6950 (0.09%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 6
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Bladder cancer recurrent
         subjects affected / exposed
    1 / 6950 (0.01%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder neoplasm
         subjects affected / exposed
    4 / 6950 (0.06%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bladder papilloma
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma recurrent
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bone cancer
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bowen’s disease
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain neoplasm benign
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    4 / 6950 (0.06%)
    5 / 6950 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Carcinoid tumour pulmonary
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Central nervous system neoplasm
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cholangiocarcinoma
         subjects affected / exposed
    3 / 6950 (0.04%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Cholesteatoma
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Chronic myeloid leukaemia
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Colon adenoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    6 / 6950 (0.09%)
    9 / 6950 (0.13%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 9
         deaths causally related to treatment / all
    0 / 4
    0 / 3
    Colon cancer metastatic
         subjects affected / exposed
    3 / 6950 (0.04%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    Colon neoplasm
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Diffuse large B-cell lymphoma
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diffuse large B-cell lymphoma stage IV
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Endometrial adenocarcinoma
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Fallopian tube cancer
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Follicular thyroid cancer
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder cancer
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastric cancer
         subjects affected / exposed
    3 / 6950 (0.04%)
    6 / 6950 (0.09%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 3
    0 / 4
    Gastrointestinal carcinoma
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Gastrointestinal stromal tumour
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal tract adenoma
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glioblastoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatic cancer
         subjects affected / exposed
    6 / 6950 (0.09%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 5
    0 / 2
    Hepatic cancer metastatic
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatic neoplasm
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Hypergammaglobulinaemia benign monoclonal
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal adenocarcinoma
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    2 / 6950 (0.03%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive lobular breast carcinoma
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive papillary breast carcinoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large cell lung cancer
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Large intestine benign neoplasm
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal cancer
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung adenocarcinoma
         subjects affected / exposed
    6 / 6950 (0.09%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 4
    0 / 0
    Lung adenocarcinoma metastatic
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Lung adenocarcinoma stage III
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    4 / 6950 (0.06%)
    6 / 6950 (0.09%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 4
    0 / 6
    Lung neoplasm
         subjects affected / exposed
    3 / 6950 (0.04%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    13 / 6950 (0.19%)
    22 / 6950 (0.32%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 22
         deaths causally related to treatment / all
    0 / 10
    0 / 18
    Lymphoma
         subjects affected / exposed
    3 / 6950 (0.04%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Malignant fibrous histiocytoma of bone
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malignant lymphoma unclassifiable high grade
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant mast cell neoplasm
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    4 / 6950 (0.06%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Malignant melanoma in situ
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant neoplasm of ampulla of Vater
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Malignant palate neoplasm
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Mesothelioma
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to adrenals
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to bone
         subjects affected / exposed
    4 / 6950 (0.06%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    Metastases to central nervous system
         subjects affected / exposed
    2 / 6950 (0.03%)
    4 / 6950 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    Metastases to gastrointestinal tract
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metastases to liver
         subjects affected / exposed
    5 / 6950 (0.07%)
    5 / 6950 (0.07%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 5
    0 / 4
    Metastases to lung
         subjects affected / exposed
    1 / 6950 (0.01%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to lymph nodes
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to peritoneum
         subjects affected / exposed
    0 / 6950 (0.00%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Metastases to stomach
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastasis
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metastatic carcinoma of the bladder
         subjects affected / exposed
    1 / 6950 (0.01%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Metastatic gastric cancer
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Metastatic malignant melanoma
         subjects affected / exposed
    2 / 6950 (0.03%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Metastatic neoplasm
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Metastatic renal cell carcinoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metastatic squamous cell carcinoma
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Neoplasm malignant
         subjects affected / exposed
    3 / 6950 (0.04%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Neoplasm prostate
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Non-Hodgkin’s lymphoma
         subjects affected / exposed
    3 / 6950 (0.04%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Non-small cell lung cancer stage IV
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Oesophageal adenocarcinoma
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Oesophageal adenocarcinoma metastatic
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Oesophageal cancer metastatic
         subjects affected / exposed
    1 / 6950 (0.01%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Oesophageal carcinoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    6 / 6950 (0.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 5
    Oesophageal squamous cell carcinoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Ovarian cancer
         subjects affected / exposed
    0 / 6950 (0.00%)
    4 / 6950 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 4
    Ovarian cancer recurrent
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ovarian epithelial cancer
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian germ cell teratoma benign
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    10 / 6950 (0.14%)
    7 / 6950 (0.10%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 7
         deaths causally related to treatment / all
    0 / 10
    0 / 7
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    2 / 6950 (0.03%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 2
    0 / 3
    Pancreatic neoplasm
         subjects affected / exposed
    0 / 6950 (0.00%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Pancreatic neuroendocrine tumour
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraganglion neoplasm
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parathyroid tumour benign
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (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
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    18 / 6950 (0.26%)
    19 / 6950 (0.27%)
         occurrences causally related to treatment / all
    0 / 18
    0 / 19
         deaths causally related to treatment / all
    0 / 5
    0 / 3
    Prostate cancer metastatic
         subjects affected / exposed
    2 / 6950 (0.03%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Prostate cancer recurrent
         subjects affected / exposed
    0 / 6950 (0.00%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Prostate cancer stage IV
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Prostatic adenoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    4 / 6950 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Rectal adenoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Rectal cancer recurrent
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (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
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal cancer metastatic
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    4 / 6950 (0.06%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Renal cell carcinoma recurrent
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal oncocytoma
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salivary gland cancer
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sarcoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin cancer
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Small cell lung cancer metastatic
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Small intestine adenocarcinoma
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Squamous cell carcinoma
         subjects affected / exposed
    3 / 6950 (0.04%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Squamous cell carcinoma of skin
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (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 the oral cavity
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sweat gland tumour
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    T-cell lymphoma
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Throat cancer
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Thyroid cancer
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tongue neoplasm malignant stage unspecified
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma metastatic
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urethral neoplasm
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulval cancer
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Allergic granulomatous angiitis
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Amyloidosis
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic reaction
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Accidental death
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Administration site erythema
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Administration site pain
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adverse drug reaction
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac death
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Chest discomfort
         subjects affected / exposed
    3 / 6950 (0.04%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    19 / 6950 (0.27%)
    20 / 6950 (0.29%)
         occurrences causally related to treatment / all
    0 / 19
    0 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cyst
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (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
    29 / 6950 (0.42%)
    17 / 6950 (0.24%)
         occurrences causally related to treatment / all
    0 / 29
    0 / 17
         deaths causally related to treatment / all
    0 / 29
    0 / 17
    Device battery issue
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device deposit issue
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device leakage
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device occlusion
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drowning
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Generalised oedema
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ill-defined disorder
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incarcerated hernia
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inflammation
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    12 / 6950 (0.17%)
    9 / 6950 (0.13%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 9
         deaths causally related to treatment / all
    0 / 11
    0 / 9
    Non-cardiac chest pain
         subjects affected / exposed
    4 / 6950 (0.06%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Organ failure
         subjects affected / exposed
    1 / 6950 (0.01%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Peripheral swelling
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 6950 (0.01%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    3 / 6950 (0.04%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    Sudden death
         subjects affected / exposed
    4 / 6950 (0.06%)
    13 / 6950 (0.19%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 13
         deaths causally related to treatment / all
    0 / 4
    0 / 13
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Thrombosis in device
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Abnormal behaviour
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute psychosis
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Affective disorder
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol withdrawal syndrome
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety disorder
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breathing-related sleep disorder
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Confusional state
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    3 / 6950 (0.04%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Depressed mood
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    3 / 6950 (0.04%)
    4 / 6950 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder due to a general medical condition
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Panic attack
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Panic disorder
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Schizoaffective disorder bipolar type
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Schizophrenia
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somatoform disorder
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Atrophic vulvovaginitis
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign prostatic hyperplasia
         subjects affected / exposed
    7 / 6950 (0.10%)
    9 / 6950 (0.13%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast dysplasia
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic obstruction
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatomegaly
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectocele
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    4 / 6950 (0.06%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal prolapse
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal ulceration
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accident
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Accidental overdose
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (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
    5 / 6950 (0.07%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back injury
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone fissure
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carbon monoxide poisoning
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cervical vertebral fracture
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Chest injury
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Compression fracture
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    3 / 6950 (0.04%)
    4 / 6950 (0.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    5 / 6950 (0.07%)
    4 / 6950 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery reocclusion
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery restenosis
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis postoperative
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye penetration
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Face injury
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    4 / 6950 (0.06%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Fall
         subjects affected / exposed
    5 / 6950 (0.07%)
    8 / 6950 (0.12%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Femoral neck fracture
         subjects affected / exposed
    6 / 6950 (0.09%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Femur fracture
         subjects affected / exposed
    15 / 6950 (0.22%)
    10 / 6950 (0.14%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Fibula fracture
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    2 / 6950 (0.03%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (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
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gun shot wound
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    1 / 6950 (0.01%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    4 / 6950 (0.06%)
    5 / 6950 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Hip fracture
         subjects affected / exposed
    2 / 6950 (0.03%)
    7 / 6950 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Humerus fracture
         subjects affected / exposed
    6 / 6950 (0.09%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Jaw fracture
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 6950 (0.00%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    2 / 6950 (0.03%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Kidney contusion
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb crushing injury
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    2 / 6950 (0.03%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    2 / 6950 (0.03%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (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
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Muscle rupture
         subjects affected / exposed
    2 / 6950 (0.03%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 6950 (0.00%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    1 / 6950 (0.01%)
    3 / 6950 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    4 / 6950 (0.06%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumothorax traumatic
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural complication
         subjects affected / exposed
    2 / 6950 (0.03%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    3 / 6950 (0.04%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural pulmonary embolism
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound complication
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural intestinal perforation
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (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 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pubis fracture
         subjects affected / exposed
    3 / 6950 (0.04%)
    2 / 6950 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    5 / 6950 (0.07%)
    5 / 6950 (0.07%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory fume inhalation disorder
         subjects affected / exposed
    1 / 6950 (0.01%)
    0 / 6950 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Rib fracture
         subjects affected / exposed
    7 / 6950 (0.10%)
    6 / 6950 (0.09%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 6950 (0.01%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin wound
         subjects affected / exposed
    0 / 6950 (0.00%)
    1 / 6950 (0.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
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