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    Clinical Trial Results:
    Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy

    Summary
    EudraCT number
    2004-000193-31
    Trial protocol
    GB  
    Global end of trial date

    Results information
    Results version number
    v2(current)
    This version publication date
    13 Aug 2023
    First version publication date
    27 Feb 2021
    Other versions
    v1
    Version creation reason
    • New data added to full data set
    Adding recently completed arms of the STAMPEDE trial

    Trial information

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    Trial identification
    Sponsor protocol code
    PR08
    Additional study identifiers
    ISRCTN number
    ISRCTN78818544
    US NCT number
    NCT00268476
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    CTA: 20363/0404/001, MREC: 04/MRE07/35, Previous IRAS (Minimal Data Set): 31586
    Sponsors
    Sponsor organisation name
    University College London
    Sponsor organisation address
    Gower Street, London, United Kingdom, WC1E6BT
    Public contact
    STAMPEDE Trial Team, MRCCTU at UCL, mrcctu.stampede@ucl.ac.uk
    Scientific contact
    STAMPEDE Trial Team, MRCCTU at UCL, 44 20 7670 4938, laura.murphy@ucl.ac.uk
    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
    Interim
    Date of interim/final analysis
    19 May 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    This study aims to look at how to improve the way in which prostate cancer is currently managed i.e. by adding new treatments to the standard of care, whether it can enable men to live longer or, by modifying the type of hormone therapy, live at least as long and enjoy a better quality of life. The principal research question for most arms is whether the treatment concerned improves overall survival; however some comparisons such as metformin are being looked at for other reasons.
    Protection of trial subjects
    In routine care
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    04 Oct 2004
    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
    Switzerland: 49
    Country: Number of subjects enrolled
    United Kingdom: 7052
    Worldwide total number of subjects
    7101
    EEA total number of subjects
    0
    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)
    2658
    From 65 to 84 years
    4439
    85 years and over
    4

    Subject disposition

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    Recruitment
    Recruitment details
    First patient randomised 17Oct2005

    Pre-assignment
    Screening details
    Screening data not available centrally

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Arm A (SOC for B,C,E comparisons)
    Arm description
    Reference patients for A vs B, C , E
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Arm B
    Arm description
    Zoledronic acid
    Arm type
    Experimental

    Investigational medicinal product name
    Zoledronic acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion in administration system
    Routes of administration
    Intravenous use
    Dosage and administration details
    4mg at six 3-weekly cycles, then 4-weekly until 2 years

    Arm title
    Arm C
    Arm description
    Docetaxel
    Arm type
    Experimental

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    75mg/m2 for six 3-weekly cycles

    Arm title
    Arm E
    Arm description
    Zoledronic Acid and Docetaxel
    Arm type
    Experimental

    Investigational medicinal product name
    Zoledronic acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion in administration system
    Routes of administration
    Intravenous use
    Dosage and administration details
    4mg at six 3-weekly cycles, then 4-weekly until 2 years

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion in administration system
    Routes of administration
    Intravenous use
    Dosage and administration details
    75mg/m2 for six 3-weekly cycles

    Arm title
    Arm A (SOC for D,F comparisons)
    Arm description
    Reference patients for A vs D, F
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Arm D
    Arm description
    Celecoxib
    Arm type
    Experimental

    Investigational medicinal product name
    Celecoxib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    400mg twice a day for 1 year

    Arm title
    Arm F
    Arm description
    Zoledronic Acid and Celecoxib
    Arm type
    Experimental

    Investigational medicinal product name
    Zoledronic acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion in administration system
    Routes of administration
    Intravenous use
    Dosage and administration details
    4mg at six 3-weekly cycles, then 4-weekly until 2 years

    Investigational medicinal product name
    Celecoxib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    400mg twice a day for 1 year

    Arm title
    Arm A (SOC - G comparison)
    Arm description
    Reference patients for arm G
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Arm G
    Arm description
    Abiraterone
    Arm type
    Experimental

    Investigational medicinal product name
    Abiraterone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1000mg

    Investigational medicinal product name
    Prednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5mg

    Arm title
    Arm A (SOC - J comparison)
    Arm description
    Reference patients for J comparison
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Arm J
    Arm description
    Enzalutamide and Abiraterone
    Arm type
    Experimental

    Investigational medicinal product name
    Enzalutamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    160mg

    Investigational medicinal product name
    Abiraterone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1000mg

    Investigational medicinal product name
    Prednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5mg

    Number of subjects in period 1
    Arm A (SOC for B,C,E comparisons) Arm B Arm C Arm E Arm A (SOC for D,F comparisons) Arm D Arm F Arm A (SOC - G comparison) Arm G Arm A (SOC - J comparison) Arm J
    Started
    1184
    593
    592
    593
    622
    312
    311
    957
    960
    987
    989
    Completed
    1184
    593
    592
    593
    622
    312
    311
    957
    960
    987
    989

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A (SOC for B,C,E comparisons)
    Reporting group description
    Reference patients for A vs B, C , E

    Reporting group title
    Arm B
    Reporting group description
    Zoledronic acid

    Reporting group title
    Arm C
    Reporting group description
    Docetaxel

    Reporting group title
    Arm E
    Reporting group description
    Zoledronic Acid and Docetaxel

    Reporting group title
    Arm A (SOC for D,F comparisons)
    Reporting group description
    Reference patients for A vs D, F

    Reporting group title
    Arm D
    Reporting group description
    Celecoxib

    Reporting group title
    Arm F
    Reporting group description
    Zoledronic Acid and Celecoxib

    Reporting group title
    Arm A (SOC - G comparison)
    Reporting group description
    Reference patients for arm G

    Reporting group title
    Arm G
    Reporting group description
    Abiraterone

    Reporting group title
    Arm A (SOC - J comparison)
    Reporting group description
    Reference patients for J comparison

    Reporting group title
    Arm J
    Reporting group description
    Enzalutamide and Abiraterone

    Reporting group values
    Arm A (SOC for B,C,E comparisons) Arm B Arm C Arm E Arm A (SOC for D,F comparisons) Arm D Arm F Arm A (SOC - G comparison) Arm G Arm A (SOC - J comparison) Arm J Total
    Number of subjects
    1184 593 592 593 622 312 311 957 960 987 989 7101
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    0 0 0 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    521 265 270 252 294 139 146 322 326 269 291 2658
        From 65-84 years
    663 328 322 341 328 173 164 635 633 717 697 4439
        85 years and over
    0 0 0 0 0 0 1 0 1 1 1 4
    Gender categorical
    Units: Subjects
        Female
    0 0 0 0 0 0 0 0 0 0 0 0
        Male
    1184 593 592 593 622 312 311 957 960 987 989 7101
    Subject analysis sets

    Subject analysis set title
    Arm A (SOC for B,C,E comparisons)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Reference patients (ABCE comparison)

    Subject analysis set title
    Arm B (ZA)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Experimental group, AB comparison

    Subject analysis set title
    Arm C (doce)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Arm A vs C

    Subject analysis set title
    Arm E (doce+ZA)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Docetaxel and Zoledronic acid

    Subject analysis set title
    Arm A (SOC for D,F comparisons)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Reference patients (ADF comparisons)

    Subject analysis set title
    Arm D (cel)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Arm A vs D

    Subject analysis set title
    Arm F (cel+ZA)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Arm A vs F

    Subject analysis set title
    Arm A (SOC G comparison)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Control arm for G comparison

    Subject analysis set title
    Arm G
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Abiraterone + prednisolone

    Subject analysis set title
    Arm A (SOC J comparison)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Reference patients for A vs J

    Subject analysis set title
    Arm J
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Enzalutamide and Abiraterone

    Subject analysis sets values
    Arm A (SOC for B,C,E comparisons) Arm B (ZA) Arm C (doce) Arm E (doce+ZA) Arm A (SOC for D,F comparisons) Arm D (cel) Arm F (cel+ZA) Arm A (SOC G comparison) Arm G Arm A (SOC J comparison) Arm J
    Number of subjects
    1184
    593
    592
    593
    622
    312
    311
    957
    960
    987
    989
    Age categorical
    Units: Subjects
        In utero
    0
    0
    0
    0
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
    0
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
    0
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
    0
    0
    0
    0
        Children (2-11 years)
    0
    0
    0
    0
    0
    0
    0
        Adolescents (12-17 years)
    0
    0
    0
    0
    0
    0
    0
        Adults (18-64 years)
    521
    265
    270
    252
    294
    139
    146
    322
    326
        From 65-84 years
    663
    328
    322
    341
    328
    173
    164
    635
    633
        85 years and over
    0
    0
    0
    0
    0
    0
    1
    1
    Age continuous
    Units:
        
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    ±
    Gender categorical
    Units: Subjects
        Female
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Male
    1184
    593
    592
    593
    622
    312
    311
    957
    960

    End points

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    End points reporting groups
    Reporting group title
    Arm A (SOC for B,C,E comparisons)
    Reporting group description
    Reference patients for A vs B, C , E

    Reporting group title
    Arm B
    Reporting group description
    Zoledronic acid

    Reporting group title
    Arm C
    Reporting group description
    Docetaxel

    Reporting group title
    Arm E
    Reporting group description
    Zoledronic Acid and Docetaxel

    Reporting group title
    Arm A (SOC for D,F comparisons)
    Reporting group description
    Reference patients for A vs D, F

    Reporting group title
    Arm D
    Reporting group description
    Celecoxib

    Reporting group title
    Arm F
    Reporting group description
    Zoledronic Acid and Celecoxib

    Reporting group title
    Arm A (SOC - G comparison)
    Reporting group description
    Reference patients for arm G

    Reporting group title
    Arm G
    Reporting group description
    Abiraterone

    Reporting group title
    Arm A (SOC - J comparison)
    Reporting group description
    Reference patients for J comparison

    Reporting group title
    Arm J
    Reporting group description
    Enzalutamide and Abiraterone

    Subject analysis set title
    Arm A (SOC for B,C,E comparisons)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Reference patients (ABCE comparison)

    Subject analysis set title
    Arm B (ZA)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Experimental group, AB comparison

    Subject analysis set title
    Arm C (doce)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Arm A vs C

    Subject analysis set title
    Arm E (doce+ZA)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Docetaxel and Zoledronic acid

    Subject analysis set title
    Arm A (SOC for D,F comparisons)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Reference patients (ADF comparisons)

    Subject analysis set title
    Arm D (cel)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Arm A vs D

    Subject analysis set title
    Arm F (cel+ZA)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Arm A vs F

    Subject analysis set title
    Arm A (SOC G comparison)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Control arm for G comparison

    Subject analysis set title
    Arm G
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Abiraterone + prednisolone

    Subject analysis set title
    Arm A (SOC J comparison)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Reference patients for A vs J

    Subject analysis set title
    Arm J
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Enzalutamide and Abiraterone

    Primary: Overall survival

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    End point title
    Overall survival
    End point description
    End point type
    Primary
    End point timeframe
    Event driven analysis
    End point values
    Arm A (SOC for B,C,E comparisons) Arm B (ZA) Arm C (doce) Arm E (doce+ZA) Arm A (SOC for D,F comparisons) Arm D (cel) Arm F (cel+ZA) Arm A (SOC G comparison) Arm G Arm A (SOC J comparison) Arm J
    Number of subjects analysed
    1184
    593
    592
    593
    622
    312
    311
    957
    960
    987
    989
    Units: Patients
        Died
    415
    201
    175
    187
    303
    143
    138
    522
    396
    391
    290
    Statistical analysis title
    Zoledronic Acid vs SOC
    Comparison groups
    Arm A (SOC for B,C,E comparisons) v Arm B (ZA)
    Number of subjects included in analysis
    1777
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.45
    Method
    Logrank
    Parameter type
    Cox proportional hazard
    Point estimate
    0.94
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.79
         upper limit
    1.11
    Statistical analysis title
    Docetaxel vs SOC
    Comparison groups
    Arm A (SOC for B,C,E comparisons) v Arm C (doce)
    Number of subjects included in analysis
    1776
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.006
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.66
         upper limit
    0.93
    Statistical analysis title
    Docetaxel+Zoledronic Acid vs SOC
    Comparison groups
    Arm A (SOC for B,C,E comparisons) v Arm E (doce+ZA)
    Number of subjects included in analysis
    1777
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.022
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.69
         upper limit
    0.97
    Statistical analysis title
    Celecoxib vs SOC
    Comparison groups
    Arm D (cel) v Arm A (SOC for D,F comparisons)
    Number of subjects included in analysis
    934
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.847
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.98
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.8
         upper limit
    1.2
    Statistical analysis title
    Celecoxib + Zoledronic acid vs SOC
    Comparison groups
    Arm A (SOC for D,F comparisons) v Arm F (cel+ZA)
    Number of subjects included in analysis
    933
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.13
    Method
    Logrank
    Parameter type
    Cox proportional hazard
    Point estimate
    0.86
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.7
         upper limit
    1.05
    Statistical analysis title
    Abiraterone vs SOC
    Comparison groups
    Arm A (SOC G comparison) v Arm G
    Number of subjects included in analysis
    1917
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.62
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.54
         upper limit
    0.71
    Statistical analysis title
    Enzalutamide and Abiraterone vs SOC
    Comparison groups
    Arm A (SOC J comparison) v Arm J
    Number of subjects included in analysis
    1976
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.0001
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.55
         upper limit
    0.74

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Events to March 4 2015 for A vs B,C,E comparisons Events to December 15 2015 for A vs D,F comparisons Events to July 3 2022 for A vs G/J comparisons
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    CTCAE
    Dictionary version
    4.0
    Reporting groups
    Reporting group title
    SOC (Arm A, ABCE comparison)
    Reporting group description
    Reference patients, Arm A, randomised between A,B,C,E

    Reporting group title
    ZA (Arm B)
    Reporting group description
    Experimental patients, AB comparison

    Reporting group title
    Doce (Arm C)
    Reporting group description
    Arm C docetaxel patients

    Reporting group title
    Doce+ZA (Arm E)
    Reporting group description
    Docetaxel plus Zoledronic acid

    Reporting group title
    SOC (Arm A, ADF comparison)
    Reporting group description
    Reference patients, Arm A, randomised between A,D,F

    Reporting group title
    Celecoxib (Arm D)
    Reporting group description
    Experimental arm, celecoxib comparison

    Reporting group title
    Celecoxib + ZA
    Reporting group description
    (Arm F)

    Reporting group title
    SOC (Arm A, G comparison)
    Reporting group description
    -

    Reporting group title
    Abiraterone (Arm G)
    Reporting group description
    -

    Reporting group title
    SOC (Arm A, J comparison)
    Reporting group description
    -

    Reporting group title
    Enzalutamide + Abiraterone (Arm J)
    Reporting group description
    -

    Serious adverse events
    SOC (Arm A, ABCE comparison) ZA (Arm B) Doce (Arm C) Doce+ZA (Arm E) SOC (Arm A, ADF comparison) Celecoxib (Arm D) Celecoxib + ZA SOC (Arm A, G comparison) Abiraterone (Arm G) SOC (Arm A, J comparison) Enzalutamide + Abiraterone (Arm J)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    117 / 1184 (9.88%)
    80 / 593 (13.49%)
    176 / 592 (29.73%)
    209 / 593 (35.24%)
    74 / 622 (11.90%)
    40 / 312 (12.82%)
    64 / 311 (20.58%)
    144 / 957 (15.05%)
    281 / 960 (29.27%)
    156 / 987 (15.81%)
    302 / 989 (30.54%)
         number of deaths (all causes)
    415
    201
    175
    187
    303
    143
    138
    522
    396
    391
    290
         number of deaths resulting from adverse events
    7
    2
    3
    8
    6
    2
    5
    4
    14
    1
    16
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    5 / 957 (0.52%)
    3 / 960 (0.31%)
    0 / 987 (0.00%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 5
    0 / 4
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 1184 (0.08%)
    0 / 593 (0.00%)
    1 / 592 (0.17%)
    0 / 593 (0.00%)
    1 / 622 (0.16%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    5 / 989 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    4 / 593 (0.67%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    2 / 311 (0.64%)
    1 / 957 (0.10%)
    2 / 960 (0.21%)
    1 / 987 (0.10%)
    4 / 989 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 5
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 1
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    4 / 960 (0.42%)
    3 / 987 (0.30%)
    6 / 989 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 5
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Vascular - other
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Surgical and medical procedures
    Surgical - other
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 1184 (0.17%)
    0 / 593 (0.00%)
    1 / 592 (0.17%)
    2 / 593 (0.34%)
    1 / 622 (0.16%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 1
    1 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    1 / 1184 (0.08%)
    0 / 593 (0.00%)
    4 / 592 (0.68%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    2 / 960 (0.21%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fever
         subjects affected / exposed
    3 / 1184 (0.25%)
    2 / 593 (0.34%)
    6 / 592 (1.01%)
    17 / 593 (2.87%)
    2 / 622 (0.32%)
    0 / 312 (0.00%)
    2 / 311 (0.64%)
    4 / 957 (0.42%)
    4 / 960 (0.42%)
    4 / 987 (0.41%)
    9 / 989 (0.91%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    5 / 6
    5 / 18
    0 / 2
    0 / 0
    0 / 2
    0 / 4
    0 / 4
    0 / 4
    1 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 1184 (0.00%)
    1 / 593 (0.17%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    1 / 960 (0.10%)
    1 / 987 (0.10%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    2 / 1184 (0.17%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    1 / 593 (0.17%)
    1 / 622 (0.16%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    2 / 1184 (0.17%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    2 / 593 (0.34%)
    2 / 622 (0.32%)
    1 / 312 (0.32%)
    1 / 311 (0.32%)
    0 / 957 (0.00%)
    2 / 960 (0.21%)
    1 / 987 (0.10%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 1
    1 / 1
    0 / 0
    0 / 2
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General - other
         subjects affected / exposed
    10 / 1184 (0.84%)
    11 / 593 (1.85%)
    18 / 592 (3.04%)
    17 / 593 (2.87%)
    8 / 622 (1.29%)
    6 / 312 (1.92%)
    4 / 311 (1.29%)
    10 / 957 (1.04%)
    27 / 960 (2.81%)
    8 / 987 (0.81%)
    16 / 989 (1.62%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 11
    5 / 20
    0 / 19
    0 / 8
    0 / 6
    0 / 4
    0 / 10
    0 / 27
    0 / 9
    3 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 5
    Fall
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    6 / 960 (0.63%)
    3 / 987 (0.30%)
    6 / 989 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 6
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 1184 (0.08%)
    0 / 593 (0.00%)
    8 / 592 (1.35%)
    4 / 593 (0.67%)
    1 / 622 (0.16%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    8 / 8
    4 / 4
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    Social - other
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    2 / 592 (0.34%)
    1 / 593 (0.17%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    2 / 960 (0.21%)
    1 / 987 (0.10%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    4 / 1184 (0.34%)
    3 / 593 (0.51%)
    5 / 592 (0.84%)
    5 / 593 (0.84%)
    2 / 622 (0.32%)
    0 / 312 (0.00%)
    3 / 311 (0.96%)
    7 / 957 (0.73%)
    11 / 960 (1.15%)
    6 / 987 (0.61%)
    5 / 989 (0.51%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    4 / 6
    2 / 5
    0 / 2
    0 / 0
    0 / 4
    0 / 7
    0 / 13
    1 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Respiratory - other
         subjects affected / exposed
    14 / 1184 (1.18%)
    10 / 593 (1.69%)
    22 / 592 (3.72%)
    22 / 593 (3.71%)
    11 / 622 (1.77%)
    7 / 312 (2.24%)
    6 / 311 (1.93%)
    15 / 957 (1.57%)
    24 / 960 (2.50%)
    9 / 987 (0.91%)
    12 / 989 (1.21%)
         occurrences causally related to treatment / all
    0 / 15
    0 / 10
    8 / 23
    5 / 23
    0 / 12
    0 / 7
    0 / 6
    0 / 17
    0 / 28
    0 / 9
    0 / 14
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    1 / 3
    0 / 1
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    1 / 592 (0.17%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    1 / 312 (0.32%)
    1 / 311 (0.32%)
    1 / 957 (0.10%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    3 / 989 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 2
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric - other
         subjects affected / exposed
    1 / 1184 (0.08%)
    1 / 593 (0.17%)
    2 / 592 (0.34%)
    0 / 593 (0.00%)
    1 / 622 (0.16%)
    0 / 312 (0.00%)
    1 / 311 (0.32%)
    0 / 957 (0.00%)
    4 / 960 (0.42%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    1 / 987 (0.10%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Thrombocytopenia
         subjects affected / exposed
    1 / 1184 (0.08%)
    0 / 593 (0.00%)
    1 / 592 (0.17%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations - other
         subjects affected / exposed
    2 / 1184 (0.17%)
    1 / 593 (0.17%)
    5 / 592 (0.84%)
    11 / 593 (1.85%)
    1 / 622 (0.16%)
    1 / 312 (0.32%)
    2 / 311 (0.64%)
    1 / 957 (0.10%)
    4 / 960 (0.42%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    4 / 5
    7 / 12
    0 / 1
    0 / 1
    0 / 2
    0 / 1
    1 / 4
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bilirubin conjugated increased
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    7 / 1184 (0.59%)
    4 / 593 (0.67%)
    4 / 592 (0.68%)
    5 / 593 (0.84%)
    5 / 622 (0.80%)
    2 / 312 (0.64%)
    1 / 311 (0.32%)
    7 / 957 (0.73%)
    17 / 960 (1.77%)
    14 / 987 (1.42%)
    23 / 989 (2.33%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
    1 / 4
    0 / 5
    0 / 5
    0 / 2
    0 / 1
    0 / 7
    1 / 17
    0 / 14
    4 / 25
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 2
    0 / 1
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 4
    Arrhythmia
         subjects affected / exposed
    2 / 1184 (0.17%)
    1 / 593 (0.17%)
    2 / 592 (0.34%)
    6 / 593 (1.01%)
    0 / 622 (0.00%)
    2 / 312 (0.64%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    2 / 960 (0.21%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    2 / 7
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heart failure
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    1 / 312 (0.32%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    1 / 960 (0.10%)
    1 / 987 (0.10%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac - other
         subjects affected / exposed
    7 / 1184 (0.59%)
    7 / 593 (1.18%)
    10 / 592 (1.69%)
    9 / 593 (1.52%)
    3 / 622 (0.48%)
    3 / 312 (0.96%)
    6 / 311 (1.93%)
    8 / 957 (0.84%)
    31 / 960 (3.23%)
    12 / 987 (1.22%)
    24 / 989 (2.43%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 7
    1 / 10
    0 / 9
    0 / 3
    0 / 3
    1 / 6
    0 / 8
    3 / 33
    0 / 12
    6 / 25
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 4
    Chest pain
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    2 / 960 (0.21%)
    0 / 987 (0.00%)
    4 / 989 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 1184 (0.00%)
    2 / 593 (0.34%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    2 / 960 (0.21%)
    0 / 987 (0.00%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system - other
         subjects affected / exposed
    12 / 1184 (1.01%)
    5 / 593 (0.84%)
    7 / 592 (1.18%)
    14 / 593 (2.36%)
    8 / 622 (1.29%)
    1 / 312 (0.32%)
    6 / 311 (1.93%)
    15 / 957 (1.57%)
    23 / 960 (2.40%)
    7 / 987 (0.71%)
    18 / 989 (1.82%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 5
    2 / 7
    0 / 14
    0 / 10
    0 / 1
    1 / 7
    0 / 15
    0 / 26
    1 / 7
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    2 / 960 (0.21%)
    1 / 987 (0.10%)
    6 / 989 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 1
    3 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stroke
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    2 / 957 (0.21%)
    1 / 960 (0.10%)
    2 / 987 (0.20%)
    7 / 989 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 1184 (0.42%)
    3 / 593 (0.51%)
    2 / 592 (0.34%)
    2 / 593 (0.34%)
    1 / 622 (0.16%)
    1 / 312 (0.32%)
    3 / 311 (0.96%)
    7 / 957 (0.73%)
    6 / 960 (0.63%)
    4 / 987 (0.41%)
    4 / 989 (0.40%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
    1 / 2
    0 / 2
    0 / 1
    0 / 1
    0 / 3
    0 / 10
    1 / 9
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    7 / 1184 (0.59%)
    3 / 593 (0.51%)
    77 / 592 (13.01%)
    65 / 593 (10.96%)
    4 / 622 (0.64%)
    0 / 312 (0.00%)
    2 / 311 (0.64%)
    2 / 957 (0.21%)
    3 / 960 (0.31%)
    14 / 987 (1.42%)
    9 / 989 (0.91%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
    79 / 83
    66 / 73
    0 / 4
    0 / 0
    0 / 2
    0 / 2
    0 / 4
    11 / 14
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 1184 (0.08%)
    0 / 593 (0.00%)
    3 / 592 (0.51%)
    9 / 593 (1.52%)
    1 / 622 (0.16%)
    0 / 312 (0.00%)
    1 / 311 (0.32%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    1 / 987 (0.10%)
    3 / 989 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 3
    9 / 9
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood - other
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    ear - other
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Eye - other
         subjects affected / exposed
    1 / 1184 (0.08%)
    1 / 593 (0.17%)
    2 / 592 (0.34%)
    2 / 593 (0.34%)
    1 / 622 (0.16%)
    0 / 312 (0.00%)
    1 / 311 (0.32%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    3 / 989 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 2
    0 / 2
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Conjunctivitis
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    4 / 1184 (0.34%)
    4 / 593 (0.67%)
    2 / 592 (0.34%)
    7 / 593 (1.18%)
    3 / 622 (0.48%)
    1 / 312 (0.32%)
    6 / 311 (1.93%)
    8 / 957 (0.84%)
    11 / 960 (1.15%)
    4 / 987 (0.41%)
    6 / 989 (0.61%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    2 / 2
    0 / 7
    0 / 3
    1 / 1
    0 / 6
    0 / 8
    0 / 12
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 1184 (0.25%)
    1 / 593 (0.17%)
    3 / 592 (0.51%)
    1 / 593 (0.17%)
    3 / 622 (0.48%)
    1 / 312 (0.32%)
    1 / 311 (0.32%)
    2 / 957 (0.21%)
    2 / 960 (0.21%)
    1 / 987 (0.10%)
    3 / 989 (0.30%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    1 / 3
    0 / 1
    0 / 3
    0 / 1
    0 / 1
    0 / 2
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    5 / 1184 (0.42%)
    1 / 593 (0.17%)
    8 / 592 (1.35%)
    10 / 593 (1.69%)
    4 / 622 (0.64%)
    0 / 312 (0.00%)
    3 / 311 (0.96%)
    2 / 957 (0.21%)
    12 / 960 (1.25%)
    2 / 987 (0.20%)
    6 / 989 (0.61%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    5 / 8
    5 / 11
    0 / 4
    0 / 0
    0 / 3
    0 / 2
    0 / 13
    1 / 2
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    2 / 592 (0.34%)
    6 / 593 (1.01%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    1 / 311 (0.32%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    3 / 7
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 1184 (0.17%)
    2 / 593 (0.34%)
    3 / 592 (0.51%)
    6 / 593 (1.01%)
    2 / 622 (0.32%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    2 / 957 (0.21%)
    6 / 960 (0.63%)
    3 / 987 (0.30%)
    5 / 989 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    1 / 3
    2 / 7
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    1 / 7
    1 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    1 / 592 (0.17%)
    1 / 593 (0.17%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    2 / 1184 (0.17%)
    1 / 593 (0.17%)
    2 / 592 (0.34%)
    5 / 593 (0.84%)
    0 / 622 (0.00%)
    1 / 312 (0.32%)
    1 / 311 (0.32%)
    7 / 957 (0.73%)
    5 / 960 (0.52%)
    6 / 987 (0.61%)
    9 / 989 (0.91%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
    0 / 5
    0 / 5
    0 / 0
    1 / 1
    0 / 1
    0 / 12
    0 / 5
    0 / 6
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Gastrointestinal - other
         subjects affected / exposed
    11 / 1184 (0.93%)
    5 / 593 (0.84%)
    12 / 592 (2.03%)
    16 / 593 (2.70%)
    5 / 622 (0.80%)
    1 / 312 (0.32%)
    7 / 311 (2.25%)
    19 / 957 (1.99%)
    28 / 960 (2.92%)
    18 / 987 (1.82%)
    17 / 989 (1.72%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 5
    2 / 12
    4 / 19
    0 / 6
    0 / 1
    1 / 7
    0 / 19
    0 / 30
    0 / 23
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Dyspepsia
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    2 / 960 (0.21%)
    0 / 987 (0.00%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatobiliary - other
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    1 / 593 (0.17%)
    0 / 622 (0.00%)
    1 / 312 (0.32%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    0 / 960 (0.00%)
    2 / 987 (0.20%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    2 / 960 (0.21%)
    1 / 987 (0.10%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Nail discolouration
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    1 / 592 (0.17%)
    1 / 593 (0.17%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 1184 (0.00%)
    1 / 593 (0.17%)
    1 / 592 (0.17%)
    2 / 593 (0.34%)
    0 / 622 (0.00%)
    2 / 312 (0.64%)
    0 / 311 (0.00%)
    1 / 957 (0.10%)
    3 / 960 (0.31%)
    2 / 987 (0.20%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    1 / 3
    0 / 0
    1 / 2
    0 / 0
    0 / 1
    1 / 3
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin - other
         subjects affected / exposed
    1 / 1184 (0.08%)
    1 / 593 (0.17%)
    5 / 592 (0.84%)
    6 / 593 (1.01%)
    1 / 622 (0.16%)
    0 / 312 (0.00%)
    2 / 311 (0.64%)
    1 / 957 (0.10%)
    11 / 960 (1.15%)
    2 / 987 (0.20%)
    4 / 989 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 5
    2 / 7
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 12
    0 / 3
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    1 / 987 (0.10%)
    4 / 989 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    4 / 1184 (0.34%)
    2 / 593 (0.34%)
    0 / 592 (0.00%)
    2 / 593 (0.34%)
    2 / 622 (0.32%)
    0 / 312 (0.00%)
    2 / 311 (0.64%)
    1 / 957 (0.10%)
    6 / 960 (0.63%)
    3 / 987 (0.30%)
    6 / 989 (0.61%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 2
    0 / 1
    0 / 7
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Haematuria
         subjects affected / exposed
    2 / 1184 (0.17%)
    2 / 593 (0.34%)
    0 / 592 (0.00%)
    3 / 593 (0.51%)
    2 / 622 (0.32%)
    0 / 312 (0.00%)
    1 / 311 (0.32%)
    7 / 957 (0.73%)
    7 / 960 (0.73%)
    4 / 987 (0.41%)
    5 / 989 (0.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 4
    0 / 2
    0 / 0
    0 / 1
    0 / 13
    1 / 11
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    4 / 1184 (0.34%)
    3 / 593 (0.51%)
    1 / 592 (0.17%)
    3 / 593 (0.51%)
    2 / 622 (0.32%)
    0 / 312 (0.00%)
    2 / 311 (0.64%)
    4 / 957 (0.42%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 1
    0 / 3
    0 / 2
    0 / 0
    0 / 2
    0 / 4
    0 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    1 / 312 (0.32%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary - other
         subjects affected / exposed
    18 / 1184 (1.52%)
    9 / 593 (1.52%)
    5 / 592 (0.84%)
    8 / 593 (1.35%)
    10 / 622 (1.61%)
    5 / 312 (1.60%)
    5 / 311 (1.61%)
    15 / 957 (1.57%)
    24 / 960 (2.50%)
    9 / 987 (0.91%)
    12 / 989 (1.21%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 9
    0 / 5
    0 / 8
    0 / 12
    0 / 5
    0 / 6
    0 / 17
    0 / 28
    0 / 9
    0 / 14
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    2 / 960 (0.21%)
    0 / 987 (0.00%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary frequency
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstruction
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    5 / 957 (0.52%)
    2 / 960 (0.21%)
    10 / 987 (1.01%)
    3 / 989 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 6
    0 / 2
    0 / 11
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    3 / 1184 (0.25%)
    2 / 593 (0.34%)
    3 / 592 (0.51%)
    1 / 593 (0.17%)
    3 / 622 (0.48%)
    1 / 312 (0.32%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    4 / 960 (0.42%)
    2 / 987 (0.20%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 3
    0 / 1
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 4
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 1184 (0.08%)
    1 / 593 (0.17%)
    0 / 592 (0.00%)
    1 / 593 (0.17%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    4 / 960 (0.42%)
    1 / 987 (0.10%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal - other
         subjects affected / exposed
    13 / 1184 (1.10%)
    15 / 593 (2.53%)
    12 / 592 (2.03%)
    38 / 593 (6.41%)
    7 / 622 (1.13%)
    6 / 312 (1.92%)
    9 / 311 (2.89%)
    8 / 957 (0.84%)
    22 / 960 (2.29%)
    11 / 987 (1.11%)
    34 / 989 (3.44%)
         occurrences causally related to treatment / all
    0 / 13
    10 / 15
    3 / 13
    20 / 41
    0 / 7
    0 / 6
    4 / 9
    0 / 8
    0 / 28
    0 / 14
    0 / 36
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    2 / 960 (0.21%)
    2 / 987 (0.20%)
    4 / 989 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    5 / 1184 (0.42%)
    2 / 593 (0.34%)
    6 / 592 (1.01%)
    4 / 593 (0.67%)
    2 / 622 (0.32%)
    1 / 312 (0.32%)
    2 / 311 (0.64%)
    8 / 957 (0.84%)
    16 / 960 (1.67%)
    9 / 987 (0.91%)
    20 / 989 (2.02%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
    2 / 6
    0 / 5
    0 / 2
    0 / 1
    0 / 2
    0 / 9
    1 / 18
    0 / 9
    1 / 24
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 1184 (0.08%)
    0 / 593 (0.00%)
    1 / 592 (0.17%)
    1 / 593 (0.17%)
    1 / 622 (0.16%)
    1 / 312 (0.32%)
    3 / 311 (0.96%)
    0 / 957 (0.00%)
    2 / 960 (0.21%)
    0 / 987 (0.00%)
    7 / 989 (0.71%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 1
    0 / 3
    0 / 0
    0 / 2
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections - other
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    6 / 960 (0.63%)
    2 / 987 (0.20%)
    5 / 989 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 7
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    Abdominal infection
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    2 / 989 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    3 / 957 (0.31%)
    26 / 960 (2.71%)
    10 / 987 (1.01%)
    21 / 989 (2.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 34
    0 / 12
    0 / 29
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 1
    Sepsis
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    2 / 960 (0.21%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Glucose tolerance decreased
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    1 / 592 (0.17%)
    1 / 593 (0.17%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    1 / 311 (0.32%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 1184 (0.08%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    1 / 311 (0.32%)
    1 / 957 (0.10%)
    5 / 960 (0.52%)
    0 / 987 (0.00%)
    4 / 989 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    1 / 5
    0 / 0
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anorexia nervosa
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    1 / 593 (0.17%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    1 / 1184 (0.08%)
    0 / 593 (0.00%)
    1 / 592 (0.17%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    2 / 957 (0.21%)
    1 / 960 (0.10%)
    1 / 987 (0.10%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    1 / 592 (0.17%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    1 / 592 (0.17%)
    1 / 593 (0.17%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    1 / 311 (0.32%)
    1 / 957 (0.10%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    0 / 989 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition - other
         subjects affected / exposed
    0 / 1184 (0.00%)
    2 / 593 (0.34%)
    1 / 592 (0.17%)
    4 / 593 (0.67%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    1 / 960 (0.10%)
    0 / 987 (0.00%)
    4 / 989 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 8
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    0 / 957 (0.00%)
    0 / 960 (0.00%)
    0 / 987 (0.00%)
    1 / 989 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    SOC (Arm A, ABCE comparison) ZA (Arm B) Doce (Arm C) Doce+ZA (Arm E) SOC (Arm A, ADF comparison) Celecoxib (Arm D) Celecoxib + ZA SOC (Arm A, G comparison) Abiraterone (Arm G) SOC (Arm A, J comparison) Enzalutamide + Abiraterone (Arm J)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1152 / 1184 (97.30%)
    579 / 593 (97.64%)
    571 / 592 (96.45%)
    560 / 593 (94.44%)
    605 / 622 (97.27%)
    292 / 312 (93.59%)
    297 / 311 (95.50%)
    946 / 957 (98.85%)
    953 / 960 (99.27%)
    974 / 987 (98.68%)
    975 / 989 (98.58%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    84 / 1184 (7.09%)
    50 / 593 (8.43%)
    44 / 592 (7.43%)
    30 / 593 (5.06%)
    35 / 622 (5.63%)
    39 / 312 (12.50%)
    27 / 311 (8.68%)
    180 / 957 (18.81%)
    368 / 960 (38.33%)
    190 / 987 (19.25%)
    554 / 989 (56.02%)
         occurrences all number
    129
    90
    74
    42
    47
    63
    43
    349
    955
    443
    1864
    Hot flush
         subjects affected / exposed
    968 / 1184 (81.76%)
    462 / 593 (77.91%)
    454 / 592 (76.69%)
    442 / 593 (74.54%)
    495 / 622 (79.58%)
    229 / 312 (73.40%)
    222 / 311 (71.38%)
    819 / 957 (85.58%)
    851 / 960 (88.65%)
    863 / 987 (87.44%)
    899 / 989 (90.90%)
         occurrences all number
    5324
    2400
    2425
    2356
    2877
    1321
    1268
    5295
    6524
    5792
    7236
    General disorders and administration site conditions
    Fever
         subjects affected / exposed
    29 / 1184 (2.45%)
    38 / 593 (6.41%)
    49 / 592 (8.28%)
    70 / 593 (11.80%)
    13 / 622 (2.09%)
    6 / 312 (1.92%)
    17 / 311 (5.47%)
    35 / 957 (3.66%)
    50 / 960 (5.21%)
    48 / 987 (4.86%)
    66 / 989 (6.67%)
         occurrences all number
    39
    51
    58
    84
    19
    8
    17
    39
    55
    60
    79
    Fatigue
         subjects affected / exposed
    632 / 1184 (53.38%)
    342 / 593 (57.67%)
    431 / 592 (72.80%)
    427 / 593 (72.01%)
    333 / 622 (53.54%)
    151 / 312 (48.40%)
    165 / 311 (53.05%)
    612 / 957 (63.95%)
    706 / 960 (73.54%)
    720 / 987 (72.95%)
    870 / 989 (87.97%)
         occurrences all number
    1999
    1144
    1616
    1607
    1080
    424
    536
    2441
    3557
    3132
    5374
    Oedema
         subjects affected / exposed
    164 / 1184 (13.85%)
    72 / 593 (12.14%)
    159 / 592 (26.86%)
    142 / 593 (23.95%)
    97 / 622 (15.59%)
    55 / 312 (17.63%)
    51 / 311 (16.40%)
    172 / 957 (17.97%)
    235 / 960 (24.48%)
    237 / 987 (24.01%)
    245 / 989 (24.77%)
         occurrences all number
    350
    124
    354
    283
    207
    100
    85
    414
    657
    569
    584
    Influenza like illness
         subjects affected / exposed
    97 / 1184 (8.19%)
    215 / 593 (36.26%)
    87 / 592 (14.70%)
    140 / 593 (23.61%)
    63 / 622 (10.13%)
    27 / 312 (8.65%)
    74 / 311 (23.79%)
    57 / 957 (5.96%)
    106 / 960 (11.04%)
    46 / 987 (4.66%)
    79 / 989 (7.99%)
         occurrences all number
    125
    363
    119
    210
    84
    36
    136
    66
    133
    53
    85
    Pain
         subjects affected / exposed
    363 / 1184 (30.66%)
    240 / 593 (40.47%)
    188 / 592 (31.76%)
    234 / 593 (39.46%)
    187 / 622 (30.06%)
    90 / 312 (28.85%)
    94 / 311 (30.23%)
    285 / 957 (29.78%)
    325 / 960 (33.85%)
    232 / 987 (23.51%)
    215 / 989 (21.74%)
         occurrences all number
    720
    485
    384
    501
    364
    162
    180
    575
    585
    379
    368
    General - other
         subjects affected / exposed
    99 / 1184 (8.36%)
    62 / 593 (10.46%)
    86 / 592 (14.53%)
    93 / 593 (15.68%)
    70 / 622 (11.25%)
    24 / 312 (7.69%)
    14 / 311 (4.50%)
    81 / 957 (8.46%)
    123 / 960 (12.81%)
    66 / 987 (6.69%)
    120 / 989 (12.13%)
         occurrences all number
    121
    79
    108
    132
    82
    24
    17
    109
    189
    98
    159
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    39 / 1184 (3.29%)
    21 / 593 (3.54%)
    58 / 592 (9.80%)
    42 / 593 (7.08%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    35 / 957 (3.66%)
    41 / 960 (4.27%)
    28 / 987 (2.84%)
    38 / 989 (3.84%)
         occurrences all number
    47
    24
    69
    53
    0
    0
    0
    47
    52
    30
    46
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    586 / 1184 (49.49%)
    296 / 593 (49.92%)
    277 / 592 (46.79%)
    281 / 593 (47.39%)
    308 / 622 (49.52%)
    127 / 312 (40.71%)
    135 / 311 (43.41%)
    518 / 957 (54.13%)
    555 / 960 (57.81%)
    524 / 987 (53.09%)
    591 / 989 (59.76%)
         occurrences all number
    3230
    1587
    1545
    1628
    1851
    740
    820
    3040
    3929
    3227
    4160
    Gynaecomastia
         subjects affected / exposed
    84 / 1184 (7.09%)
    38 / 593 (6.41%)
    29 / 592 (4.90%)
    37 / 593 (6.24%)
    47 / 622 (7.56%)
    19 / 312 (6.09%)
    17 / 311 (5.47%)
    170 / 957 (17.76%)
    170 / 960 (17.71%)
    264 / 987 (26.75%)
    296 / 989 (29.93%)
         occurrences all number
    145
    57
    41
    58
    74
    41
    32
    390
    472
    758
    1021
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    129 / 1184 (10.90%)
    56 / 593 (9.44%)
    95 / 592 (16.05%)
    79 / 593 (13.32%)
    59 / 622 (9.49%)
    19 / 312 (6.09%)
    29 / 311 (9.32%)
    155 / 957 (16.20%)
    289 / 960 (30.10%)
    226 / 987 (22.90%)
    218 / 989 (22.04%)
         occurrences all number
    229
    73
    152
    136
    103
    31
    36
    315
    638
    456
    443
    Dyspnoea
         subjects affected / exposed
    171 / 1184 (14.44%)
    82 / 593 (13.83%)
    122 / 592 (20.61%)
    117 / 593 (19.73%)
    82 / 622 (13.18%)
    45 / 312 (14.42%)
    38 / 311 (12.22%)
    212 / 957 (22.15%)
    306 / 960 (31.88%)
    262 / 987 (26.55%)
    320 / 989 (32.36%)
         occurrences all number
    362
    154
    256
    253
    169
    99
    72
    546
    920
    703
    945
    Rhinitis
         subjects affected / exposed
    62 / 1184 (5.24%)
    32 / 593 (5.40%)
    41 / 592 (6.93%)
    39 / 593 (6.58%)
    38 / 622 (6.11%)
    17 / 312 (5.45%)
    21 / 311 (6.75%)
    40 / 957 (4.18%)
    73 / 960 (7.60%)
    44 / 987 (4.46%)
    67 / 989 (6.77%)
         occurrences all number
    102
    55
    71
    61
    65
    24
    39
    65
    112
    61
    105
    Respiratory - other
         subjects affected / exposed
    95 / 1184 (8.02%)
    58 / 593 (9.78%)
    77 / 592 (13.01%)
    72 / 593 (12.14%)
    64 / 622 (10.29%)
    26 / 312 (8.33%)
    32 / 311 (10.29%)
    66 / 957 (6.90%)
    143 / 960 (14.90%)
    62 / 987 (6.28%)
    99 / 989 (10.01%)
         occurrences all number
    150
    88
    115
    103
    96
    38
    39
    112
    229
    83
    135
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    291 / 1184 (24.58%)
    152 / 593 (25.63%)
    189 / 592 (31.93%)
    170 / 593 (28.67%)
    154 / 622 (24.76%)
    69 / 312 (22.12%)
    78 / 311 (25.08%)
    266 / 957 (27.80%)
    336 / 960 (35.00%)
    329 / 987 (33.33%)
    385 / 989 (38.93%)
         occurrences all number
    784
    362
    457
    416
    389
    142
    197
    780
    1105
    1051
    1336
    Anxiety
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    60 / 957 (6.27%)
    103 / 960 (10.73%)
    152 / 987 (15.40%)
    209 / 989 (21.13%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    98
    172
    340
    533
    Depression
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    54 / 957 (5.64%)
    92 / 960 (9.58%)
    143 / 987 (14.49%)
    214 / 989 (21.64%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    94
    166
    286
    533
    Libido decreased
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    38 / 957 (3.97%)
    67 / 960 (6.98%)
    104 / 987 (10.54%)
    137 / 989 (13.85%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    43
    103
    198
    263
    Psychiatric - other
         subjects affected / exposed
    195 / 1184 (16.47%)
    79 / 593 (13.32%)
    100 / 592 (16.89%)
    95 / 593 (16.02%)
    104 / 622 (16.72%)
    48 / 312 (15.38%)
    44 / 311 (14.15%)
    180 / 957 (18.81%)
    236 / 960 (24.58%)
    147 / 987 (14.89%)
    204 / 989 (20.63%)
         occurrences all number
    482
    171
    191
    197
    274
    75
    94
    402
    636
    298
    369
    Investigations
    Neutrophil count
         subjects affected / exposed
    46 / 1184 (3.89%)
    25 / 593 (4.22%)
    114 / 592 (19.26%)
    111 / 593 (18.72%)
    28 / 622 (4.50%)
    11 / 312 (3.53%)
    9 / 311 (2.89%)
    48 / 957 (5.02%)
    80 / 960 (8.33%)
    77 / 987 (7.80%)
    99 / 989 (10.01%)
         occurrences all number
    82
    37
    160
    148
    47
    26
    12
    81
    129
    119
    193
    Alkaline phosphatase increased
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    28 / 957 (2.93%)
    47 / 960 (4.90%)
    100 / 987 (10.13%)
    96 / 989 (9.71%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    35
    62
    156
    197
    cholesterol high
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    28 / 957 (2.93%)
    45 / 960 (4.69%)
    45 / 987 (4.56%)
    60 / 989 (6.07%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    37
    79
    79
    112
    Investigations - other
         subjects affected / exposed
    297 / 1184 (25.08%)
    161 / 593 (27.15%)
    160 / 592 (27.03%)
    153 / 593 (25.80%)
    173 / 622 (27.81%)
    83 / 312 (26.60%)
    90 / 311 (28.94%)
    323 / 957 (33.75%)
    432 / 960 (45.00%)
    305 / 987 (30.90%)
    363 / 989 (36.70%)
         occurrences all number
    587
    301
    353
    317
    361
    180
    201
    713
    1311
    626
    866
    Aspartate aminotransferase increased
         subjects affected / exposed
    32 / 1184 (2.70%)
    17 / 593 (2.87%)
    21 / 592 (3.55%)
    22 / 593 (3.71%)
    16 / 622 (2.57%)
    7 / 312 (2.24%)
    11 / 311 (3.54%)
    34 / 957 (3.55%)
    81 / 960 (8.44%)
    38 / 987 (3.85%)
    139 / 989 (14.05%)
         occurrences all number
    58
    31
    39
    28
    34
    11
    21
    57
    171
    59
    243
    Alanine aminotransferase increased
         subjects affected / exposed
    110 / 1184 (9.29%)
    55 / 593 (9.27%)
    69 / 592 (11.66%)
    63 / 593 (10.62%)
    53 / 622 (8.52%)
    29 / 312 (9.29%)
    26 / 311 (8.36%)
    145 / 957 (15.15%)
    267 / 960 (27.81%)
    170 / 987 (17.22%)
    389 / 989 (39.33%)
         occurrences all number
    218
    102
    139
    140
    116
    73
    52
    281
    605
    334
    902
    Platelet count decreased
         subjects affected / exposed
    28 / 1184 (2.36%)
    21 / 593 (3.54%)
    26 / 592 (4.39%)
    37 / 593 (6.24%)
    15 / 622 (2.41%)
    11 / 312 (3.53%)
    11 / 311 (3.54%)
    44 / 957 (4.60%)
    55 / 960 (5.73%)
    58 / 987 (5.88%)
    62 / 989 (6.27%)
         occurrences all number
    60
    38
    60
    74
    40
    29
    37
    99
    118
    113
    121
    Weight increased
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    45 / 957 (4.70%)
    60 / 960 (6.25%)
    170 / 987 (17.22%)
    159 / 989 (16.08%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    54
    90
    269
    254
    Cardiac disorders
    cardiac - other
         subjects affected / exposed
    60 / 1184 (5.07%)
    24 / 593 (4.05%)
    35 / 592 (5.91%)
    24 / 593 (4.05%)
    35 / 622 (5.63%)
    18 / 312 (5.77%)
    16 / 311 (5.14%)
    64 / 957 (6.69%)
    96 / 960 (10.00%)
    35 / 987 (3.55%)
    63 / 989 (6.37%)
         occurrences all number
    133
    37
    59
    36
    79
    33
    32
    97
    163
    46
    115
    Arrhythmia
         subjects affected / exposed
    41 / 1184 (3.46%)
    21 / 593 (3.54%)
    21 / 592 (3.55%)
    18 / 593 (3.04%)
    20 / 622 (3.22%)
    17 / 312 (5.45%)
    15 / 311 (4.82%)
    41 / 957 (4.28%)
    68 / 960 (7.08%)
    32 / 987 (3.24%)
    63 / 989 (6.37%)
         occurrences all number
    63
    40
    30
    28
    32
    35
    26
    61
    132
    47
    108
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    141 / 1184 (11.91%)
    75 / 593 (12.65%)
    88 / 592 (14.86%)
    93 / 593 (15.68%)
    90 / 622 (14.47%)
    40 / 312 (12.82%)
    37 / 311 (11.90%)
    137 / 957 (14.32%)
    190 / 960 (19.79%)
    151 / 987 (15.30%)
    253 / 989 (25.58%)
         occurrences all number
    252
    152
    141
    158
    169
    69
    65
    215
    389
    312
    476
    Headache
         subjects affected / exposed
    161 / 1184 (13.60%)
    86 / 593 (14.50%)
    95 / 592 (16.05%)
    98 / 593 (16.53%)
    100 / 622 (16.08%)
    35 / 312 (11.22%)
    38 / 311 (12.22%)
    120 / 957 (12.54%)
    186 / 960 (19.38%)
    139 / 987 (14.08%)
    261 / 989 (26.39%)
         occurrences all number
    334
    153
    190
    172
    202
    63
    80
    264
    383
    269
    584
    Nervous system - other
         subjects affected / exposed
    106 / 1184 (8.95%)
    64 / 593 (10.79%)
    235 / 592 (39.70%)
    206 / 593 (34.74%)
    61 / 622 (9.81%)
    42 / 312 (13.46%)
    52 / 311 (16.72%)
    104 / 957 (10.87%)
    158 / 960 (16.46%)
    146 / 987 (14.79%)
    211 / 989 (21.33%)
         occurrences all number
    163
    97
    597
    449
    96
    68
    81
    180
    307
    235
    412
    Cognitive disorder
         subjects affected / exposed
    21 / 1184 (1.77%)
    16 / 593 (2.70%)
    10 / 592 (1.69%)
    10 / 593 (1.69%)
    12 / 622 (1.93%)
    4 / 312 (1.28%)
    4 / 311 (1.29%)
    52 / 957 (5.43%)
    73 / 960 (7.60%)
    55 / 987 (5.57%)
    187 / 989 (18.91%)
         occurrences all number
    26
    21
    12
    16
    15
    6
    8
    95
    142
    84
    377
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    322 / 1184 (27.20%)
    212 / 593 (35.75%)
    228 / 592 (38.51%)
    252 / 593 (42.50%)
    172 / 622 (27.65%)
    78 / 312 (25.00%)
    108 / 311 (34.73%)
    385 / 957 (40.23%)
    489 / 960 (50.94%)
    456 / 987 (46.20%)
    502 / 989 (50.76%)
         occurrences all number
    931
    653
    691
    902
    495
    255
    370
    1300
    1966
    1559
    1978
    Eye disorders
    Vision blurred
         subjects affected / exposed
    54 / 1184 (4.56%)
    27 / 593 (4.55%)
    44 / 592 (7.43%)
    61 / 593 (10.29%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    45 / 957 (4.70%)
    67 / 960 (6.98%)
    56 / 987 (5.67%)
    82 / 989 (8.29%)
         occurrences all number
    85
    54
    73
    105
    0
    0
    0
    79
    112
    81
    146
    Eye - other
         subjects affected / exposed
    74 / 1184 (6.25%)
    41 / 593 (6.91%)
    91 / 592 (15.37%)
    97 / 593 (16.36%)
    50 / 622 (8.04%)
    19 / 312 (6.09%)
    25 / 311 (8.04%)
    53 / 957 (5.54%)
    98 / 960 (10.21%)
    50 / 987 (5.07%)
    98 / 989 (9.91%)
         occurrences all number
    113
    67
    152
    175
    74
    30
    39
    83
    166
    83
    178
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    160 / 1184 (13.51%)
    76 / 593 (12.82%)
    114 / 592 (19.26%)
    127 / 593 (21.42%)
    89 / 622 (14.31%)
    60 / 312 (19.23%)
    54 / 311 (17.36%)
    142 / 957 (14.84%)
    208 / 960 (21.67%)
    163 / 987 (16.51%)
    196 / 989 (19.82%)
         occurrences all number
    298
    131
    200
    203
    161
    95
    106
    283
    414
    305
    382
    Constipation
         subjects affected / exposed
    218 / 1184 (18.41%)
    147 / 593 (24.79%)
    207 / 592 (34.97%)
    212 / 593 (35.75%)
    125 / 622 (20.10%)
    46 / 312 (14.74%)
    70 / 311 (22.51%)
    259 / 957 (27.06%)
    333 / 960 (34.69%)
    317 / 987 (32.12%)
    394 / 989 (39.84%)
         occurrences all number
    440
    278
    389
    436
    268
    81
    147
    605
    895
    801
    987
    Diarrhoea
         subjects affected / exposed
    251 / 1184 (21.20%)
    139 / 593 (23.44%)
    247 / 592 (41.72%)
    233 / 593 (39.29%)
    134 / 622 (21.54%)
    85 / 312 (27.24%)
    77 / 311 (24.76%)
    286 / 957 (29.89%)
    337 / 960 (35.10%)
    349 / 987 (35.36%)
    419 / 989 (42.37%)
         occurrences all number
    495
    250
    499
    451
    274
    143
    133
    637
    726
    823
    954
    Dyspepsia
         subjects affected / exposed
    155 / 1184 (13.09%)
    76 / 593 (12.82%)
    137 / 592 (23.14%)
    125 / 593 (21.08%)
    97 / 622 (15.59%)
    67 / 312 (21.47%)
    57 / 311 (18.33%)
    120 / 957 (12.54%)
    181 / 960 (18.85%)
    141 / 987 (14.29%)
    187 / 989 (18.91%)
         occurrences all number
    314
    123
    245
    208
    221
    110
    102
    223
    374
    283
    350
    Flatulence
         subjects affected / exposed
    167 / 1184 (14.10%)
    79 / 593 (13.32%)
    88 / 592 (14.86%)
    78 / 593 (13.15%)
    105 / 622 (16.88%)
    48 / 312 (15.38%)
    43 / 311 (13.83%)
    149 / 957 (15.57%)
    163 / 960 (16.98%)
    205 / 987 (20.77%)
    248 / 989 (25.08%)
         occurrences all number
    395
    160
    158
    132
    252
    89
    105
    377
    357
    413
    588
    Haemorrhage
         subjects affected / exposed
    90 / 1184 (7.60%)
    36 / 593 (6.07%)
    44 / 592 (7.43%)
    46 / 593 (7.76%)
    48 / 622 (7.72%)
    15 / 312 (4.81%)
    20 / 311 (6.43%)
    79 / 957 (8.25%)
    84 / 960 (8.75%)
    77 / 987 (7.80%)
    103 / 989 (10.41%)
         occurrences all number
    148
    70
    71
    74
    81
    28
    35
    154
    139
    132
    159
    Nausea
         subjects affected / exposed
    128 / 1184 (10.81%)
    77 / 593 (12.98%)
    151 / 592 (25.51%)
    152 / 593 (25.63%)
    80 / 622 (12.86%)
    43 / 312 (13.78%)
    37 / 311 (11.90%)
    112 / 957 (11.70%)
    180 / 960 (18.75%)
    154 / 987 (15.60%)
    267 / 989 (27.00%)
         occurrences all number
    210
    131
    226
    265
    126
    57
    59
    201
    353
    252
    558
    Vomiting
         subjects affected / exposed
    61 / 1184 (5.15%)
    30 / 593 (5.06%)
    57 / 592 (9.63%)
    65 / 593 (10.96%)
    41 / 622 (6.59%)
    23 / 312 (7.37%)
    24 / 311 (7.72%)
    47 / 957 (4.91%)
    94 / 960 (9.79%)
    71 / 987 (7.19%)
    113 / 989 (11.43%)
         occurrences all number
    81
    39
    73
    88
    52
    25
    35
    63
    130
    98
    154
    Stomatitis
         subjects affected / exposed
    36 / 1184 (3.04%)
    25 / 593 (4.22%)
    153 / 592 (25.84%)
    149 / 593 (25.13%)
    22 / 622 (3.54%)
    15 / 312 (4.81%)
    18 / 311 (5.79%)
    22 / 957 (2.30%)
    35 / 960 (3.65%)
    33 / 987 (3.34%)
    35 / 989 (3.54%)
         occurrences all number
    57
    31
    210
    216
    32
    17
    26
    30
    59
    41
    39
    Gastrointestinal - other
         subjects affected / exposed
    181 / 1184 (15.29%)
    75 / 593 (12.65%)
    156 / 592 (26.35%)
    143 / 593 (24.11%)
    97 / 622 (15.59%)
    52 / 312 (16.67%)
    40 / 311 (12.86%)
    164 / 957 (17.14%)
    230 / 960 (23.96%)
    179 / 987 (18.14%)
    236 / 989 (23.86%)
         occurrences all number
    294
    108
    260
    268
    168
    74
    64
    290
    384
    299
    424
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    65 / 1184 (5.49%)
    35 / 593 (5.90%)
    37 / 592 (6.25%)
    44 / 593 (7.42%)
    27 / 622 (4.34%)
    27 / 312 (8.65%)
    27 / 311 (8.68%)
    53 / 957 (5.54%)
    116 / 960 (12.08%)
    41 / 987 (4.15%)
    59 / 989 (5.97%)
         occurrences all number
    105
    69
    71
    78
    49
    52
    44
    77
    195
    60
    78
    Skin and subcutaneous tissue disorders
    Nail discolouration
         subjects affected / exposed
    61 / 1184 (5.15%)
    37 / 593 (6.24%)
    258 / 592 (43.58%)
    194 / 593 (32.72%)
    35 / 622 (5.63%)
    16 / 312 (5.13%)
    23 / 311 (7.40%)
    53 / 957 (5.54%)
    64 / 960 (6.67%)
    66 / 987 (6.69%)
    88 / 989 (8.90%)
         occurrences all number
    109
    51
    583
    406
    53
    21
    47
    98
    103
    148
    168
    Rash
         subjects affected / exposed
    117 / 1184 (9.88%)
    67 / 593 (11.30%)
    73 / 592 (12.33%)
    70 / 593 (11.80%)
    70 / 622 (11.25%)
    48 / 312 (15.38%)
    41 / 311 (13.18%)
    92 / 957 (9.61%)
    158 / 960 (16.46%)
    110 / 987 (11.14%)
    124 / 989 (12.54%)
         occurrences all number
    199
    91
    104
    116
    126
    77
    67
    167
    262
    166
    213
    Alopecia
         subjects affected / exposed
    7 / 1184 (0.59%)
    2 / 593 (0.34%)
    80 / 592 (13.51%)
    69 / 593 (11.64%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    8 / 957 (0.84%)
    6 / 960 (0.63%)
    22 / 987 (2.23%)
    32 / 989 (3.24%)
         occurrences all number
    7
    3
    136
    118
    0
    0
    0
    12
    16
    30
    50
    Skin - other
         subjects affected / exposed
    202 / 1184 (17.06%)
    89 / 593 (15.01%)
    238 / 592 (40.20%)
    216 / 593 (36.42%)
    112 / 622 (18.01%)
    37 / 312 (11.86%)
    51 / 311 (16.40%)
    171 / 957 (17.87%)
    259 / 960 (26.98%)
    146 / 987 (14.79%)
    238 / 989 (24.06%)
         occurrences all number
    318
    136
    449
    400
    176
    67
    69
    297
    489
    262
    444
    Renal and urinary disorders
    Urinary frequency
         subjects affected / exposed
    605 / 1184 (51.10%)
    308 / 593 (51.94%)
    307 / 592 (51.86%)
    279 / 593 (47.05%)
    310 / 622 (49.84%)
    146 / 312 (46.79%)
    138 / 311 (44.37%)
    637 / 957 (66.56%)
    666 / 960 (69.38%)
    731 / 987 (74.06%)
    733 / 989 (74.12%)
         occurrences all number
    2125
    957
    969
    934
    1130
    514
    438
    2706
    3221
    3435
    3869
    Acute kidney injury
         subjects affected / exposed
    92 / 1184 (7.77%)
    71 / 593 (11.97%)
    49 / 592 (8.28%)
    75 / 593 (12.65%)
    51 / 622 (8.20%)
    25 / 312 (8.01%)
    57 / 311 (18.33%)
    27 / 957 (2.82%)
    37 / 960 (3.85%)
    48 / 987 (4.86%)
    49 / 989 (4.95%)
         occurrences all number
    183
    232
    95
    201
    101
    47
    171
    35
    48
    75
    76
    Haematuria
         subjects affected / exposed
    57 / 1184 (4.81%)
    23 / 593 (3.88%)
    22 / 592 (3.72%)
    35 / 593 (5.90%)
    40 / 622 (6.43%)
    21 / 312 (6.73%)
    14 / 311 (4.50%)
    78 / 957 (8.15%)
    96 / 960 (10.00%)
    83 / 987 (8.41%)
    78 / 989 (7.89%)
         occurrences all number
    86
    34
    30
    44
    60
    30
    16
    110
    129
    122
    117
    Chronic kidney disease
         subjects affected / exposed
    92 / 1184 (7.77%)
    71 / 593 (11.97%)
    49 / 592 (8.28%)
    75 / 593 (12.65%)
    51 / 622 (8.20%)
    25 / 312 (8.01%)
    57 / 311 (18.33%)
    102 / 957 (10.66%)
    114 / 960 (11.88%)
    84 / 987 (8.51%)
    96 / 989 (9.71%)
         occurrences all number
    183
    232
    95
    201
    101
    47
    171
    233
    339
    187
    245
    Renal - other
         subjects affected / exposed
    189 / 1184 (15.96%)
    88 / 593 (14.84%)
    97 / 592 (16.39%)
    94 / 593 (15.85%)
    102 / 622 (16.40%)
    55 / 312 (17.63%)
    39 / 311 (12.54%)
    219 / 957 (22.88%)
    196 / 960 (20.42%)
    240 / 987 (24.32%)
    235 / 989 (23.76%)
         occurrences all number
    301
    132
    154
    150
    157
    90
    60
    387
    362
    472
    435
    Urinary urgency
         subjects affected / exposed
    0 / 1184 (0.00%)
    0 / 593 (0.00%)
    0 / 592 (0.00%)
    0 / 593 (0.00%)
    0 / 622 (0.00%)
    0 / 312 (0.00%)
    0 / 311 (0.00%)
    111 / 957 (11.60%)
    118 / 960 (12.29%)
    281 / 987 (28.47%)
    324 / 989 (32.76%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    164
    204
    605
    774
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    144 / 1184 (12.16%)
    69 / 593 (11.64%)
    64 / 592 (10.81%)
    64 / 593 (10.79%)
    87 / 622 (13.99%)
    28 / 312 (8.97%)
    35 / 311 (11.25%)
    89 / 957 (9.30%)
    137 / 960 (14.27%)
    230 / 987 (23.30%)
    267 / 989 (27.00%)
         occurrences all number
    246
    109
    107
    97
    154
    45
    71
    125
    215
    467
    561
    Myalgia
         subjects affected / exposed
    184 / 1184 (15.54%)
    109 / 593 (18.38%)
    133 / 592 (22.47%)
    141 / 593 (23.78%)
    101 / 622 (16.24%)
    34 / 312 (10.90%)
    53 / 311 (17.04%)
    170 / 957 (17.76%)
    208 / 960 (21.67%)
    206 / 987 (20.87%)
    300 / 989 (30.33%)
         occurrences all number
    316
    186
    226
    265
    158
    60
    99
    340
    378
    414
    598
    Arthralgia
         subjects affected / exposed
    303 / 1184 (25.59%)
    189 / 593 (31.87%)
    202 / 592 (34.12%)
    214 / 593 (36.09%)
    182 / 622 (29.26%)
    87 / 312 (27.88%)
    94 / 311 (30.23%)
    263 / 957 (27.48%)
    330 / 960 (34.38%)
    334 / 987 (33.84%)
    401 / 989 (40.55%)
         occurrences all number
    787
    426
    513
    525
    495
    220
    270
    614
    842
    813
    957
    Bone pain
         subjects affected / exposed
    436 / 1184 (36.82%)
    235 / 593 (39.63%)
    190 / 592 (32.09%)
    232 / 593 (39.12%)
    249 / 622 (40.03%)
    114 / 312 (36.54%)
    119 / 311 (38.26%)
    350 / 957 (36.57%)
    346 / 960 (36.04%)
    354 / 987 (35.87%)
    358 / 989 (36.20%)
         occurrences all number
    920
    531
    441
    517
    564
    240
    300
    683
    721
    674
    811
    Musculoskeletal - other
         subjects affected / exposed
    437 / 1184 (36.91%)
    245 / 593 (41.32%)
    247 / 592 (41.72%)
    275 / 593 (46.37%)
    254 / 622 (40.84%)
    102 / 312 (32.69%)
    117 / 311 (37.62%)
    355 / 957 (37.10%)
    416 / 960 (43.33%)
    292 / 987 (29.58%)
    343 / 989 (34.68%)
         occurrences all number
    922
    546
    549
    617
    559
    183
    228
    742
    1025
    568
    741
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    94 / 1184 (7.94%)
    57 / 593 (9.61%)
    81 / 592 (13.68%)
    83 / 593 (14.00%)
    52 / 622 (8.36%)
    27 / 312 (8.65%)
    34 / 311 (10.93%)
    90 / 957 (9.40%)
    97 / 960 (10.10%)
    90 / 987 (9.12%)
    98 / 989 (9.91%)
         occurrences all number
    119
    73
    108
    104
    64
    30
    39
    130
    147
    114
    162
    Sinusitis
         subjects affected / exposed
    37 / 1184 (3.13%)
    21 / 593 (3.54%)
    21 / 592 (3.55%)
    20 / 593 (3.37%)
    27 / 622 (4.34%)
    12 / 312 (3.85%)
    12 / 311 (3.86%)
    24 / 957 (2.51%)
    36 / 960 (3.75%)
    21 / 987 (2.13%)
    41 / 989 (4.15%)
         occurrences all number
    63
    29
    32
    28
    52
    23
    34
    39
    59
    27
    58
    Upper respiratory tract infection
         subjects affected / exposed
    116 / 1184 (9.80%)
    66 / 593 (11.13%)
    97 / 592 (16.39%)
    97 / 593 (16.36%)
    61 / 622 (9.81%)
    30 / 312 (9.62%)
    36 / 311 (11.58%)
    94 / 957 (9.82%)
    159 / 960 (16.56%)
    102 / 987 (10.33%)
    141 / 989 (14.26%)
         occurrences all number
    157
    85
    132
    128
    79
    36
    44
    125
    237
    140
    191
    Metabolism and nutrition disorders
    Hypocalcaemia
         subjects affected / exposed
    39 / 1184 (3.29%)
    64 / 593 (10.79%)
    32 / 592 (5.41%)
    57 / 593 (9.61%)
    26 / 622 (4.18%)
    16 / 312 (5.13%)
    25 / 311 (8.04%)
    35 / 957 (3.66%)
    69 / 960 (7.19%)
    37 / 987 (3.75%)
    54 / 989 (5.46%)
         occurrences all number
    55
    98
    42
    91
    42
    23
    34
    42
    96
    39
    61
    Anorexia nervosa
         subjects affected / exposed
    91 / 1184 (7.69%)
    49 / 593 (8.26%)
    73 / 592 (12.33%)
    74 / 593 (12.48%)
    56 / 622 (9.00%)
    32 / 312 (10.26%)
    35 / 311 (11.25%)
    79 / 957 (8.25%)
    110 / 960 (11.46%)
    114 / 987 (11.55%)
    182 / 989 (18.40%)
         occurrences all number
    120
    78
    85
    118
    79
    40
    47
    122
    189
    186
    354
    Glucose tolerance decreased
         subjects affected / exposed
    37 / 1184 (3.13%)
    21 / 593 (3.54%)
    29 / 592 (4.90%)
    30 / 593 (5.06%)
    20 / 622 (3.22%)
    13 / 312 (4.17%)
    10 / 311 (3.22%)
    59 / 957 (6.17%)
    110 / 960 (11.46%)
    79 / 987 (8.00%)
    88 / 989 (8.90%)
         occurrences all number
    49
    50
    53
    67
    32
    34
    15
    138
    310
    185
    258
    Metabolism - other
         subjects affected / exposed
    104 / 1184 (8.78%)
    29 / 593 (4.89%)
    46 / 592 (7.77%)
    56 / 593 (9.44%)
    45 / 622 (7.23%)
    24 / 312 (7.69%)
    13 / 311 (4.18%)
    117 / 957 (12.23%)
    124 / 960 (12.92%)
    82 / 987 (8.31%)
    115 / 989 (11.63%)
         occurrences all number
    152
    44
    56
    73
    73
    42
    16
    179
    236
    145
    186
    Hypokalaemia
         subjects affected / exposed
    16 / 1184 (1.35%)
    16 / 593 (2.70%)
    20 / 592 (3.38%)
    20 / 593 (3.37%)
    5 / 622 (0.80%)
    3 / 312 (0.96%)
    6 / 311 (1.93%)
    30 / 957 (3.13%)
    129 / 960 (13.44%)
    40 / 987 (4.05%)
    142 / 989 (14.36%)
         occurrences all number
    17
    19
    29
    28
    6
    4
    11
    32
    234
    64
    247

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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