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    Clinical Trial Results:
    A Phase 4, randomized, double-Blind, placebo-Controlled Study of continued enzalutamide treatment beyond progression in subjects with chemotherapy-naïve metastatic castration-resistant prostate cancer (CRPC).

    Summary
    EudraCT number
    		 2013-000722-54
    Trial protocol
    		 GB   ES   FI   DE   SK   BE   SE   IT   DK  
    Global end of trial date

    Results information
    Results version number
    		 v1
    This version publication date
    30 Oct 2017
    First version publication date
    30 Oct 2017
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    MDV3100-10
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01995513
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 110017
    Public contact
    Pfizer Inc., Pfizer ClinicalTrials.gov Call Center, 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, 10017
    Public contact
    Pfizer, Inc., Pfizer ClinicalTrials.gov Call Center, 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer, Inc., Pfizer ClinicalTrials.gov Call Center, 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    16 May 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Nov 2016
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To determine the efficacy of combination treatment with continued enzalutamide plus abiraterone and prednisone (or prednisolone) compared with placebo plus abiraterone and prednisone as measured by progression free survival (PFS) after prostate specific antigen (PSA) progression on treatment with enzalutamide in subjects with chemotherapy-naïve metastatic castration-resistant prostate cancer (CRPC).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    12 Nov 2013
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 4 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 234
    Country: Number of subjects enrolled
    United States: 16
    Country: Number of subjects enrolled
    Belgium: 16
    Country: Number of subjects enrolled
    Denmark: 39
    Country: Number of subjects enrolled
    Finland: 35
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    Italy: 43
    Country: Number of subjects enrolled
    Slovakia: 16
    Country: Number of subjects enrolled
    Spain: 34
    Country: Number of subjects enrolled
    Sweden: 18
    Country: Number of subjects enrolled
    United Kingdom: 52
    Worldwide total number of subjects
    509
    EEA total number of subjects
    259
    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)
    95
    From 65 to 84 years
    385
    85 years and over
    29

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study comprised of consecutive periods of open-label treatment with enzalutamide (period 1) followed by randomized, double-blind treatment with enzalutamide or placebo, each in combination with open-label abiraterone and prednisone (period 2).

    Period 1
    Period 1 title
    Open label Treatment Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Enzalutamide 160 mg
    Arm description
    		 Subjects received enzalutamide 160 milligram (mg) as four 40 mg capsules, orally once daily until disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or subject withdrawal, whichever occurred first. Subjects were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Enzalutamide
    Investigational medicinal product code
    Other name
    MDV3100
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Enzalutamide 160 mg was administered orally, once daily.

    Number of subjects in period 1
    		Enzalutamide 160 mg
    Started
    509
    Completed
    251
    Not completed
    258
         Adverse event, serious fatal
    8
         Consent withdrawn by subject
    14
         No PSA response at week 13
    43
         Adverse event, non-fatal
    35
         Ongoing as of data cutoff (07 Oct 2016)
    84
         Unspecified
    9
         Disease Progression
    64
         Protocol deviation
    1
    Period 2
    Period 2 title
    Double Blind Treatment Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg
    Arm description
    		 Subjects with confirmed prostate-specific antigen (PSA) progression at Week 21 in open label period, received enzalutamide 160 mg as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in double blind treatment period, up to disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or subject withdrawal, whichever occurred first. Subjects were followed up for 16 weeks at 4-week interval after discontinuation of study drug for survival and subsequent antineoplastic therapy for prostate cancer.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Enzalutamide
    Investigational medicinal product code
    Other name
    MDV3100
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Enzalutamide 160 mg was administered orally, once daily.

    Investigational medicinal product name
    Abiraterone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Abiraterone 1000 mg as four 250 mg tablets were administered orally, once daily.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Prednisone 10 mg as two 5 mg tablets were administered orally, once daily.

    Arm title
    		 Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Arm description
    		 Subjects with confirmed PSA progression at Week 21 in open label period, received placebo matched to enzalutamide as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in double blind treatment period, up to disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or subject withdrawal, whichever occurred first. Subjects were followed up for 16 weeks at 4-week interval after discontinuation of study drug for survival and subsequent antineoplastic therapy for prostate cancer.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matched to enzalutamide was administered orally, once daily.

    Investigational medicinal product name
    Abiraterone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Abiraterone 1000 mg as four 250 mg tablets were administered orally, once daily.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Prednisone 10 mg as two 5 mg tablets were administered orally, once daily.

    Number of subjects in period 2
    		Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Started
    126
    125
    Treated
    125
    124
    Completed
    0
    0
    Not completed
    126
    125
         Adverse event, serious fatal
    -
    1
         Consent withdrawn by subject
    4
    6
         Adverse event, non-fatal
    12
    5
         Ongoing as of data cutoff (07 Oct 2016)
    27
    18
         Unspecified
    1
    2
         Disease Progression
    82
    93

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Enzalutamide 160 mg
    Reporting group description
    		 Subjects received enzalutamide 160 milligram (mg) as four 40 mg capsules, orally once daily until disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or subject withdrawal, whichever occurred first. Subjects were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first.

    Reporting group values
    		 Enzalutamide 160 mg Total
    Number of subjects
    		 509 509
    Age Categorical
    Units: Subjects
        <65 years
    		 95 95
        65 -74 years
    		 203 203
        >=75 years
    		 211 211
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 72.3 ± 8.31 -
    Gender, Male/Female
    Units: Subjects
        Female
    		 0 0
        Male
    		 509 509

    End points

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    End points reporting groups
    Reporting group title
    Enzalutamide 160 mg
    Reporting group description
    		 Subjects received enzalutamide 160 milligram (mg) as four 40 mg capsules, orally once daily until disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or subject withdrawal, whichever occurred first. Subjects were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first.
    Reporting group title
    Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg
    Reporting group description
    		 Subjects with confirmed prostate-specific antigen (PSA) progression at Week 21 in open label period, received enzalutamide 160 mg as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in double blind treatment period, up to disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or subject withdrawal, whichever occurred first. Subjects were followed up for 16 weeks at 4-week interval after discontinuation of study drug for survival and subsequent antineoplastic therapy for prostate cancer.

    Reporting group title
    Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Reporting group description
    		 Subjects with confirmed PSA progression at Week 21 in open label period, received placebo matched to enzalutamide as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in double blind treatment period, up to disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or subject withdrawal, whichever occurred first. Subjects were followed up for 16 weeks at 4-week interval after discontinuation of study drug for survival and subsequent antineoplastic therapy for prostate cancer.

    Primary: Progression Free Survival (PFS)

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    End point title
    		 Progression Free Survival (PFS)
    End point description
    PFS = time from randomization to first documentation of radiographic progression (RP),unequivocal clinical progression or death due to any cause (death within 112 days of treatment discontinuation without objective evidence of RP),whichever occurred first as per investigator. Unequivocal disease progression was pain requiring chronic administration of analgesics, decline of prostate cancer of Eastern Cooperative Oncology Group (ECOG) performance status score to 3 or higher or initiation of new anticancer therapy/radiation therapy or surgical intervention due to tumor progression. ECOG score range= 0(no severity) to 5(maximum severity).RP for bone disease was evaluated by appearance of 2 or more new bone lesions as per Prostate Cancer Clinical Trials Working Group 2 (PCWG2) or for soft tissue disease according to RECIST v1.1. Subjects with no PFS event at analysis date were censored at last tumor assessment date prior to data cutoff date. Intent to treat (ITT) analysis set.
    End point type
    Primary
    End point timeframe
    From randomization until disease progression, last tumor assessment without disease progression or death due to any cause, whichever occurred first (up to the data cutoff date [07 Oct 2016])
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    126
    125
    Units: months
        median (confidence interval 95%)
    5.7 (4.6 to 8.1)
    5.6 (4.5 to 7.3)
    Statistical analysis title
    		 Enzalutamide vs Placebo
    Comparison groups
    Placebo+Abiraterone 1000mg+ Prednisone 10mg v Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects included in analysis
    251
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2176 [1]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.828
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.612
         upper limit
    		 1.119
    Notes
    [1] - P-value was based on log-rank test stratified by PSA response (greater than or equal to [>=] 0 percent [%] to less than [<] 30% vs >=30%) at Week 13 in the open-label period.

    Secondary: Time to Prostate Specific Antigen (PSA) Progression

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    End point title
    		 Time to Prostate Specific Antigen (PSA) Progression
    End point description
    Time from date of randomization to the date of first confirmed PSA progression as per Prostate Cancer Clinical Trials Working Group 2 (PCWG2). For subject whose PSA decreased at Week 13 after randomization, progression was defined as 25 percent (%) PSA increase relative to nadir or absolute increase of >=2 nanogram/milliliter (ng/mL) above nadir. Progression was confirmed if another assessment measured at least 3 weeks later met the criterion as well. For subject whose PSA did not decrease at Week 13 after randomization, progression was defined as 25% PSA increase relative to baseline assessed 12 weeks after baseline. Subjects who were not known to have had a PFS event at the analysis date were censored at last PSA assessment date prior to data cutoff date. ITT analysis set.
    End point type
    Secondary
    End point timeframe
    From randomization until disease progression, last tumor assessment without disease progression, whichever occurred first (up to the data cutoff date [07 Oct 2016])
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    126
    125
    Units: months
        median (confidence interval 95%)
    2.8 (2.8 to 2.9)
    2.8 (2.8 to 2.8)
    Statistical analysis title
    		 Enzalutamide vs Placebo
    Comparison groups
    Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg v Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects included in analysis
    251
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.45 [2]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.874
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.617
         upper limit
    		 1.239
    Notes
    [2] - P-value was based on log-rank test stratified by PSA response (>=0% to <30% vs >=30%) at Week 13 in the open-label period.

    Secondary: Prostate Specific Antigen (PSA) Response Rate

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    End point title
    		 Prostate Specific Antigen (PSA) Response Rate
    End point description
    PSA response rate was defined as percentage of subjects with >=30% and >=50% decrease in PSA from baseline at randomization to the maximal PSA response with a threshold of 30% and 50% respectively. PSA response was confirmed if another assessment measured at least 3 weeks later met the criterion as well. Evaluable ITT population included all subjects with a PSA value at baseline of Period 2 and at least 1 post baseline assessment. Here, N signifies those subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    From randomization until disease progression, last tumor assessment without disease progression, whichever occurred first (up to the data cutoff date [07 Oct 2016])
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    124
    122
    Units: percentage of subjects
    number (confidence interval 95%)
        >= 50%
    0.8 (0.0 to 4.4)
    2.5 (0.5 to 7.0)
        >= 30%
    2.4 (0.5 to 6.9)
    2.5 (0.5 to 7.0)
    Statistical analysis title
    		 Enzalutamide vs Placebo
    Statistical analysis description
    This analysis is reported for subjects with >=50% decrease from baseline in PSA response.
    Comparison groups
    Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg v Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects included in analysis
    246
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3101 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Response Rate
    Point estimate
    -1.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.82
         upper limit
    		 -1.51
    Notes
    [3] - P-value was based on Cochran-Mantel-Haenszel mean score test stratified by PSA response (>=0% to <30% vs >=30%) at Week 13 in the open-label period.
    Statistical analysis title
    		 Enzalutamide vs Placebo
    Statistical analysis description
    This analysis is reported for subjects with >=30% decrease from baseline in PSA response.
    Comparison groups
    Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg v Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects included in analysis
    246
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9917 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Response Rate
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.9
         upper limit
    		 3.82
    Notes
    [4] - P-value was based on Cochran-Mantel-Haenszel mean score test stratified by PSA response (>=0% to <30% vs >=30%) at Week 13 in the open-label period.

    Secondary: Objective Response Rate (ORR)

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    End point title
    		 Objective Response Rate (ORR)
    End point description
    Objective response rate as assessed by the investigator according to Response Evaluation Criteria in Solid Tumor version 1.1 (RECIST v1.1) was defined as 1) Percentage of subjects with confirmed best overall complete response (CR) and partial response (PR); 2) Percentage of subjects with CR, PR and stable disease (SD) for target lesions or non-progressive disease for non-target lesions. CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to <10 millimeter (mm) in short axis. No new lesions and disappearance of all non-target lesions. PR: >= 30% decrease in sum of diameters of target lesions, compared to the sum at baseline. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. ITT population (with measurable disease at screening) included all subjects randomly assigned to study treatment. N= subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    From randomization until CR or PR, whichever occurred first (up to the data cutoff date [07 Oct 2016])
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    38
    40
    Units: percentage of subjects
    number (confidence interval 95%)
        CR + PR
    0.0 (0.00 to 9.25)
    5.0 (0.61 to 16.92)
        CR + PR + SD
    68.4 (51.35 to 82.50)
    57.5 (40.89 to 72.96)
    Statistical analysis title
    		 Enzalutamide vs Placebo
    Statistical analysis description
    This analysis is reported for subjects with CR+PR.
    Comparison groups
    Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg v Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1653 [5]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Objective Response Rate
    Point estimate
    -5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.75
         upper limit
    		 1.75
    Notes
    [5] - P-value was based on Cochran-Mantel-Haenszel mean score test stratified by PSA response (>=0% to <30% vs >=30%) at Week 13 in the open-label period.
    Statistical analysis title
    		 Enzalutamide vs Placebo
    Statistical analysis description
    This analysis is reported for subjects with CR+PR+SD.
    Comparison groups
    Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg v Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3216 [6]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Objective Response Rate
    Point estimate
    10.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.37
         upper limit
    		 32.21
    Notes
    [6] - P-value was based on Cochran-Mantel-Haenszel mean score test stratified by PSA response (>=0% to <30% vs >=30%) at Week 13 in the open-label period.

    Secondary: Rate of Pain Progression

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    End point title
    		 Rate of Pain Progression
    End point description
    Rate of pain progression was defined as percentage of subjects with an increase of >=30% from baseline in the mean Brief Pain Inventory-Short Form (BPI-SF) pain intensity item scores of 4 items assessing average, worst, least, and intermediate pain severity. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a subject. BPI-sf includes 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). BPI-sf score range for each item was from 0=no pain to 10=worst possible pain. Total score was reported as average of individual questions ranges from 0 to 10, where lower scores indicated less pain or less pain interference. ITT analysis set. N=subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    58
    59
    Units: percentage of subjects
        number (confidence interval 95%)
    36.2 (24.0 to 49.9)
    27.1 (16.4 to 40.3)
    Statistical analysis title
    		 Enzalutamide vs Placebo
    Comparison groups
    Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg v Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects included in analysis
    117
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2963 [7]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Progression Rate
    Point estimate
    9.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.69
         upper limit
    		 25.87
    Notes
    [7] - P-value was based on Cochran-Mantel-Haenszel mean score test stratified by PSA response (>=0% to <30% vs >=30%) at Week 13 in the open-label period.

    Secondary: Time to First Use of New Antineoplastic Therapy for Prostate Cancer

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    End point title
    		 Time to First Use of New Antineoplastic Therapy for Prostate Cancer
    End point description
    It was defined as time from randomization to the date of first use of subsequent antineoplastic therapy for prostate cancer. For subjects who had not started subsequent antineoplastic therapy as of data analysis cutoff date, the time to first use of subsequent antineoplastic therapy was censored at the date of last assessment. ITT population included all subjects randomly assigned to study treatment.
    End point type
    Secondary
    End point timeframe
    From randomization until date of first use of any antineoplastic therapy (after last dose date of Period 2, up to the data cutoff date [07 Oct 2016])
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    126
    125
    Units: months
        median (confidence interval 95%)
    10.3 (8.7 to 12.1)
    8.6 (7.4 to 11.7)
    Statistical analysis title
    		 Enzalutamide vs Placebo
    Comparison groups
    Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg v Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects included in analysis
    251
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3818 [8]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.861
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.616
         upper limit
    		 1.204
    Notes
    [8] - P-value was based on log-rank test stratified by PSA response (>=0% to <30% vs >=30%) at Week 13 in the open-label period.

    Secondary: Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Global Score

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    End point title
    		 Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Global Score
    End point description
    The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess subject function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score which is the sum of all 5 domain scores and ranges from 0 to 156 with higher scores representing better quality of life. ITT population included all subjects randomly assigned to study treatment. Here, n signifies those subjects who were evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    126
    125
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =125, 123)
    116.4 ± 20.10
    119.0 ± 19.08
        Change at Week 9 (n =102, 105)
    -3.3 ± 14.90
    -2.2 ± 13.90
        Change at Week 13 (n =88, 87)
    -4.4 ± 14.44
    -0.5 ± 13.02
        Change at Week 17 (n =83, 77)
    -3.7 ± 12.40
    -2.3 ± 13.90
        Change at Week 21 (n =69, 65)
    -2.5 ± 12.33
    -2.7 ± 13.57
        Change at Week 25 (n =61, 61)
    -3.1 ± 13.47
    -2.1 ± 10.87
        Change at Week 29 (n =51, 49)
    -6.8 ± 13.98
    0.3 ± 12.10
        Change at Week 33 (n =44, 43)
    -5.9 ± 15.35
    -0.2 ± 12.90
        Change at Week 37 (n =35, 33)
    -6.1 ± 14.25
    0.9 ± 12.57
        Change at Week 41 (n =31, 29)
    -5.7 ± 12.17
    1.3 ± 14.13
        Change at Week 45 (n =28, 26)
    -6.0 ± 9.56
    -2.6 ± 16.27
        Change at Week 49 (n =27, 18)
    -4.2 ± 11.36
    1.8 ± 10.74
        Change at Week 53 (n =20, 15)
    -4.8 ± 10.17
    1.8 ± 14.68
        Change at Week 57 (n =17, 13)
    -4.3 ± 9.73
    0.1 ± 7.45
        Change at Week 61 (n =13, 10)
    -5.5 ± 10.63
    0.6 ± 12.94
        Change at Week 65 (n =13, 7)
    -7.0 ± 7.86
    1.9 ± 9.50
        Change at Week 69 (n =10, 7)
    -3.5 ± 11.37
    4.4 ± 13.29
        Change at Week 73 (n =8, 1)
    -0.7 ± 7.26
    -35.0 ± 99999
        Change at Week 77 (n =7, 2)
    -4.0 ± 9.81
    6.5 ± 30.41
        Change at Week 81 (n =2, 0)
    10.8 ± 9.24
    99999 ± 99999
        Change at Week 85 (n =2, 0)
    -5.5 ± 3.54
    99999 ± 99999
        Change at Week 89 (n =1, 0)
    -2.0 ± 99999
    99999 ± 99999
    No statistical analyses for this end point

    Secondary: Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Social/Family Well-Being Domain Scores

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    End point title
    		 Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Social/Family Well-Being Domain Scores
    End point description
    The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess subject function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain. Total subscale score range for social/family well-being domain is from 0 (worst response) to 32 (best response), where higher score indicate better quality of life. ITT population included all subjects randomly assigned to study treatment. Here, n signifies those subjects who were evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    126
    125
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =125, 123)
    22.1 ± 5.80
    22.4 ± 4.84
        Change at Week 9 (n =104, 108)
    -0.5 ± 4.33
    -0.8 ± 4.13
        Change at Week 13 (n =89, 89)
    -0.4 ± 3.46
    -0.4 ± 3.86
        Change at Week 17 (n =84, 80)
    -0.1 ± 3.68
    -0.6 ± 4.64
        Change at Week 21 (n =70, 67)
    -0.5 ± 3.24
    -1.2 ± 5.75
        Change at Week 25 (n =62, 62)
    0.1 ± 2.79
    -1.0 ± 5.25
        Change at Week 29 (n =51, 50)
    -0.1 ± 3.20
    -0.2 ± 5.18
        Change at Week 33 (n =44, 44)
    -0.2 ± 3.21
    0.0 ± 4.95
        Change at Week 37 (n =36, 33)
    -0.8 ± 3.04
    0.8 ± 2.79
        Change at Week 41 (n =31, 29)
    -1.4 ± 3.75
    -0.1 ± 3.51
        Change at Week 45 (n =28, 27)
    -0.9 ± 3.36
    -0.8 ± 3.75
        Change at Week 49 (n =27, 18)
    -0.6 ± 2.88
    0.0 ± 2.65
        Change at Week 53 (n =21, 15)
    -1.0 ± 3.15
    0.4 ± 2.56
        Change at Week 57 (n =17, 13)
    -2.0 ± 3.06
    0.2 ± 1.29
        Change at Week 61 (n =13, 10)
    -1.5 ± 2.77
    -0.2 ± 1.80
        Change at Week 65 (n =13, 7)
    -1.5 ± 2.54
    -0.5 ± 0.96
        Change at Week 69 (n =10, 7)
    -1.4 ± 2.03
    -0.5 ± 0.96
        Change at Week 73 (n =8, 1)
    -0.6 ± 3.22
    -1.0 ± 99999
        Change at Week 77 (n =7, 2)
    -0.9 ± 3.41
    -0.5 ± 0.71
        Change at Week 81 (n =2, 0)
    6.2 ± 5.42
    99999 ± 99999
        Change at Week 85 (n =2, 0)
    -1.0 ± 1.41
    99999 ± 99999
        Change at Week 89 (n =1, 0)
    0.0 ± 99999
    99999 ± 99999
    No statistical analyses for this end point

    Secondary: Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Emotional Well-Being Domain Scores

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    End point title
    		 Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Emotional Well-Being Domain Scores
    End point description
    The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess subject function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain. Total subscale score range for emotional well-being domain is from 0 (worst response) to 24 (best response), where higher score indicates better quality of life. ITT population included all subjects randomly assigned to study treatment. Here, n signifies those subjects who were evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    126
    125
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =126,124)
    18.1 ± 3.80
    18.5 ± 4.06
        Change at Week 9 (n =104, 107)
    -0.1 ± 2.81
    0.1 ± 3.40
        Change at Week 13 (n =91, 88)
    -0.1 ± 3.55
    0.2 ± 3.09
        Change at Week 17 (n =84, 79)
    -0.2 ± 3.44
    0.4 ± 2.88
        Change at Week 21 (n =71, 67)
    0.3 ± 3.48
    0.1 ± 3.36
        Change at Week 25 (n =62, 63)
    0.3 ± 2.58
    0.3 ± 3.33
        Change at Week 29 (n =51, 51)
    -0.5 ± 3.56
    0.3 ± 3.27
        Change at Week 33 (n =44, 45)
    0.1 ± 3.33
    0.9 ± 2.99
        Change at Week 37 (n =36, 34)
    -0.7 ± 4.04
    0.9 ± 2.49
        Change at Week 41 (n =31, 30)
    0.1 ± 2.99
    1.4 ± 2.60
        Change at Week 45 (n =28, 27)
    -0.5 ± 3.23
    1.2 ± 2.76
        Change at Week 49 (n =27, 19)
    0.0 ± 3.00
    1.3 ± 2.75
        Change at Week 53 (n =21, 16)
    0.1 ± 2.72
    1.2 ± 3.23
        Change at Week 57 (n =17, 14)
    -0.4 ± 2.32
    1.6 ± 2.53
        Change at Week 61 (n =13, 11)
    -0.3 ± 3.14
    1.1 ± 3.62
        Change at Week 65 (n =13, 7)
    -0.9 ± 3.57
    2.9 ± 2.54
        Change at Week 69 (n =10, 8)
    -0.5 ± 2.93
    1.5 ± 2.93
        Change at Week 73 (n =8, 2)
    1.0 ± 2.83
    -5.0 ± 5.66
        Change at Week 77 (n =7, 2)
    0.1 ± 2.67
    2.0 ± 2.83
        Change at Week 81 (n =2, 0)
    1.5 ± 3.54
    99999 ± 99999
        Change at Week 85 (n =2, 0)
    -1.5 ± 0.71
    99999 ± 99999
        Change at Week 89 (n =1, 0)
    -3.0 ± 99999
    99999 ± 99999
    No statistical analyses for this end point

    Secondary: Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Functional Well-Being Domain Scores

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    End point title
    		 Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Functional Well-Being Domain Scores
    End point description
    The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess subject function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain. Total subscale score range for functional well-being domain is from 0 (worst response) to 28 (best response), where higher score indicate better quality of life. ITT population included all subjects randomly assigned to study treatment. Here, n signifies those subjects who were evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    126
    125
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =126, 124)
    20.2 ± 5.54
    20.3 ± 5.84
        Change at Week 9 (n =104, 107)
    -1.0 ± 4.23
    -0.7 ± 4.62
        Change at Week 13 (n =91, 87)
    -1.2 ± 4.07
    -0.4 ± 4.54
        Change at Week 17 (n =84, 78)
    -1.3 ± 4.00
    -0.5 ± 4.11
        Change at Week 21 (n =71, 67)
    -1.2 ± 5.03
    -0.7 ± 4.03
        Change at Week 25 (n =62, 63)
    -1.0 ± 3.41
    -0.3 ± 4.41
        Change at Week 29 (n =51, 51)
    -2.4 ± 4.67
    -0.2 ± 4.38
        Change at Week 33 (n =44, 44)
    -2.0 ± 5.14
    -0.7 ± 4.49
        Change at Week 37 (n =36, 34)
    -1.5 ± 5.22
    0.2 ± 5.72
        Change at Week 41 (n =31, 30)
    -2.1 ± 4.44
    0.8 ± 5.74
        Change at Week 45 (n =28, 28)
    -2.0 ± 3.37
    -0.3 ± 6.28
        Change at Week 49 (n =27, 19)
    -2.1 ± 4.55
    1.5 ± 5.02
        Change at Week 53 (n =21, 16)
    -1.6 ± 4.67
    1.3 ± 4.92
        Change at Week 57 (n =17, 14)
    -1.4 ± 4.06
    2.0 ± 4.37
        Change at Week 61 (n =13, 11)
    -0.8 ± 3.34
    2.9 ± 5.56
        Change at Week 65 (n =13, 7)
    -1.2 ± 2.21
    1.7 ± 2.75
        Change at Week 69 (n =10, 8)
    0.2 ± 1.48
    2.3 ± 4.23
        Change at Week 73 (n =8, 2)
    -0.6 ± 3.02
    4.0 ± 12.73
        Change at Week 77 (n =7, 2)
    -1.6 ± 3.91
    2.5 ± 9.19
        Change at Week 81 (n =2, 0)
    -1.5 ± 7.78
    99999 ± 99999
        Change at Week 85 (n =2, 0)
    -1.5 ± 2.12
    99999 ± 99999
        Change at Week 89 (n =1, 0)
    1.0 ± 99999
    99999 ± 99999
    No statistical analyses for this end point

    Secondary: Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Prostate Cancer Domain Scores

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    End point title
    		 Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Prostate Cancer Domain Scores
    End point description
    The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess subject function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain. Total subscale score range for prostate cancer domain is from 0 (worst response) to 48 (best response), where higher score indicated better quality of life with fewer symptoms. ITT population included all subjects randomly assigned to study treatment. Here, n signifies those subjects who were evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    126
    125
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =126, 124)
    33.2 ± 6.85
    34.2 ± 6.45
        Change at Week 9 (n =104, 107)
    -0.7 ± 5.97
    -0.9 ± 5.18
        Change at Week 13 (n =90, 89)
    -1.9 ± 5.91
    -0.1 ± 5.36
        Change at Week 17 (n =84, 79)
    -1.0 ± 5.36
    -1.4 ± 5.10
        Change at Week 21 (n =71, 67)
    -0.4 ± 5.13
    -0.6 ± 4.83
        Change at Week 25 (n =61, 63)
    -0.8 ± 6.93
    -0.8 ± 4.42
        Change at Week 29 (n =52, 51)
    -1.3 ± 5.75
    -0.3 ± 4.77
        Change at Week 33 (n =44, 45)
    -1.4 ± 5.16
    -0.6 ± 4.88
        Change at Week 37 (n =35, 34)
    -1.5 ± 4.88
    -0.8 ± 4.32
        Change at Week 41 (n =31, 30)
    -1.0 ± 5.13
    -0.7 ± 5.34
        Change at Week 45 (n =28, 28)
    -0.8 ± 4.88
    -1.7 ± 7.02
        Change at Week 49 (n =27, 19)
    -0.8 ± 4.26
    -0.9 ± 4.63
        Change at Week 53 (n =20, 16)
    -1.1 ± 3.65
    -1.8 ± 5.78
        Change at Week 57 (n =17, 14)
    -0.5 ± 3.67
    -3.3 ± 4.48
        Change at Week 61 (n =13, 11)
    -2.1 ± 4.29
    -3.1 ± 5.68
        Change at Week 65 (n =13, 7)
    -2.0 ± 4.05
    -2.6 ± 6.32
        Change at Week 69 (n =10, 8)
    -1.5 ± 3.30
    1.1 ± 5.79
        Change at Week 73 (n =8, 2)
    -0.2 ± 3.17
    -6.4 ± 9.32
        Change at Week 77 (n =7, 2)
    -1.0 ± 3.71
    -1.5 ± 13.44
        Change at Week 81 (n =2, 0)
    3.1 ± 1.22
    99999 ± 99999
        Change at Week 85 (n =2, 0)
    -0.5 ± 0.71
    99999 ± 99999
        Change at Week 89 (n =1, 0)
    0.0 ± 99999
    99999 ± 99999
    No statistical analyses for this end point

    Secondary: Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Physical Well-Being Domain Scores

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    End point title
    		 Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Physical Well-Being Domain Scores
    End point description
    The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess subject function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain. Total subscale score range for physical well-being domain is from 0 (worst response) to 28 (best response), where higher score indicates better quality of life. ITT population included all subjects randomly assigned to study treatment. Here, n signifies those subjects who were evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    126
    125
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =126,124)
    22.9 ± 4.50
    23.6 ± 4.42
        Change at Week 9 (n =105, 109)
    -0.8 ± 4.04
    0.1 ± 3.20
        Change at Week 13 (n =91, 89)
    -1.0 ± 4.11
    0.0 ± 2.63
        Change at Week 17 (n =85, 80)
    -1.1 ± 3.26
    -0.3 ± 2.97
        Change at Week 21 (n =70, 68)
    -0.8 ± 3.11
    -0.8 ± 4.48
        Change at Week 25 (n =62, 63)
    -1.7 ± 4.23
    -0.4 ± 2.90
        Change at Week 29 (n =51, 51)
    -2.5 ± 4.89
    0.3 ± 2.67
        Change at Week 33 (n =44, 45)
    -2.5 ± 5.37
    0.1 ± 3.18
        Change at Week 37 (n =36, 34)
    -1.8 ± 4.50
    0.4 ± 3.13
        Change at Week 41 (n =31, 30)
    -1.5 ± 3.94
    0.4 ± 2.80
        Change at Week 45 (n =28, 28)
    -2.0 ± 3.72
    -0.4 ± 3.59
        Change at Week 49 (n =27, 19)
    -0.9 ± 3.78
    0.6 ± 2.12
        Change at Week 53 (n =21, 16)
    -0.2 ± 3.78
    0.7 ± 2.85
        Change at Week 57 (n =17, 14)
    -0.4 ± 3.25
    0.4 ± 2.37
        Change at Week 61 (n =13, 11)
    -0.8 ± 3.11
    0.4 ± 2.32
        Change at Week 65 (n =13, 7)
    -1.9 ± 4.25
    0.4 ± 1.99
        Change at Week 69 (n =10, 8)
    -0.3 ± 4.08
    -0.5 ± 2.67
        Change at Week 73 (n =8, 2)
    -0.3 ± 2.05
    -3.0 ± 5.66
        Change at Week 77 (n =7, 2)
    -0.7 ± 2.81
    4.0 ± 4.24
        Change at Week 81 (n =2, 0)
    1.5 ± 2.12
    99999 ± 99999
        Change at Week 85 (n =2, 0)
    -1.0 ± 0.0
    99999 ± 99999
        Change at Week 89 (n =1, 0)
    0.0 ± 99999
    99999 ± 99999
    No statistical analyses for this end point

    Secondary: Time to Degradation of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) Global Score

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    End point title
    		 Time to Degradation of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) Global Score
    End point description
    Time to degradation of FACT-P was defined as the time from randomization to first assessment with at least a 10-point decrease from baseline in the global FACT-P score for each subject. The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess subject function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms (prostate cancer domain). Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score which is the sum of all 5 domain scores and ranges from 0 to 156 with higher scores representing better quality of life. Subjects with no score degradation at the time of analysis data cutoff were censored at the date of last assessment showing no degradation. Evaluable ITT analysis set.
    End point type
    Secondary
    End point timeframe
    From randomization up to data cutoff date (07 Oct 2016)
    End point values
    		 Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    126
    125
    Units: months
        median (confidence interval 95%)
    4.6 (3.7 to 6.5)
    6.4 (5.5 to 13.9)
    Statistical analysis title
    		 Enzalutamide vs Placebo
    Comparison groups
    Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg v Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects included in analysis
    251
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0739 [9]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.399
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.967
         upper limit
    		 2.025
    Notes
    [9] - P-value was based on log-rank test stratified by PSA response (>=0% to <30% vs >=30%) at Week 13 in the open-label period

    Other pre-specified: Percentage of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Percentage of Subjects With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent are events between first dose of study drug and up to 30 days after last dose of study drug that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious. Safety population included all subjects who received any amount of study drug. Here, N signifies those subjects who were evaluable for this endpoint.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to data cutoff date [07 Oct 2016])
    End point values
    		 Enzalutamide 160 mg Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    509
    125
    124
    Units: percentage of subjects
    number (not applicable)
        AEs
    93.3
    89.6
    91.1
        SAEs
    27.9
    30.4
    28.2
    No statistical analyses for this end point

    Other pre-specified: Percentage of Subjects With Adverse Events (AEs) Leading to Study Drug Discontinuation

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    End point title
    		 Percentage of Subjects With Adverse Events (AEs) Leading to Study Drug Discontinuation
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Outcome of an AE was response to a question answered by the investigator: ‘Is the AE leading to study discontinuation or death?’ as ‘yes’. Safety population included all subjects who received any amount of study drug. Here, N signifies those subjects who were evaluable for this endpoint.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to data cutoff date [07 Oct 2016])
    End point values
    		 Enzalutamide 160 mg Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    509
    125
    124
    Units: percentage of subjects
        number (not applicable)
    9.8
    19.2
    12.1
    No statistical analyses for this end point

    Other pre-specified: Percentage of Subjects With Adverse Events (AEs) Leading to Death

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    End point title
    		 Percentage of Subjects With Adverse Events (AEs) Leading to Death
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Outcome of an AE was response to a question answered by the investigator: ‘Is the AE leading to study discontinuation or death?’ as ‘yes’. Safety population included all subjects who received any amount of study drug. Here, N signifies those subjects who were evaluable for this endpoint.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to data cutoff date [07 Oct 2016])
    End point values
    		 Enzalutamide 160 mg Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    509
    125
    124
    Units: percentage of subjects
        number (not applicable)
    4.7
    3.2
    2.4
    No statistical analyses for this end point

    Other pre-specified: Percentage of Subjects With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Percentage of Subjects With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator. Safety population included all subjects who received any amount of study drug. Here, N signifies those subjects who were evaluable for this endpoint.
    End point type
    Other pre-specified
    End point timeframe
    Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to data cutoff date [07 Oct 2016])
    End point values
    		 Enzalutamide 160 mg Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Number of subjects analysed
    509
    125
    124
    Units: percentage of subjects
    number (not applicable)
        AEs
    65.4
    43.2
    35.5
        SAEs
    3.5
    4.8
    4.8
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to 30 days after the last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first (up to data cutoff date [07 Oct 2016])
    Adverse event reporting additional description
    Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Enzalutamide 160 mg
    Reporting group description
    		 Subjects received enzalutamide 160 mg as four 40 mg capsules, orally once daily until disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or patient withdrawal, whichever occurs first. Subjects were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first.

    Reporting group title
    Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg
    Reporting group description
    		 Subjects with confirmed PSA progression at Week 21 in open label period, received enzalutamide 160 mg as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in double blind treatment period, up to disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or patient withdrawal, whichever occurs first. Subjects were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first.

    Reporting group title
    Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Reporting group description
    		 Subject with confirmed PSA progression at Week 21 in open label period, received placebo matched to enzalutamide as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in double blind treatment period, up to disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or patient withdrawal, whichever occurs first. Subjects were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first.

    Serious adverse events
    		 Enzalutamide 160 mg Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    142 / 509 (27.90%)
    38 / 125 (30.40%)
    35 / 124 (28.23%)
         number of deaths (all causes)
    24
    10
    10
         number of deaths resulting from adverse events
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bowen's disease
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic myelomonocytic leukaemia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngeal squamous cell carcinoma
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lentigo maligna
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung squamous cell carcinoma stage 0
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant pleural effusion
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Metastases to bone
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Metastases to spine
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastasis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastatic pain
         subjects affected / exposed
    3 / 509 (0.59%)
    3 / 125 (2.40%)
    2 / 124 (1.61%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine carcinoma metastatic
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Prostate cancer metastatic
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Transitional cell carcinoma metastatic
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic stenosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arterial rupture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphoedema
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    5 / 509 (0.98%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    0 / 1
    Fatigue
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    4 / 509 (0.79%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Balanitis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 509 (0.00%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Acetabulum fracture
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Burns third degree
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis radiation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    5 / 509 (0.98%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal injury
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure congestive
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mitral valve disease
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Myocardial ischaemia
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sick sinus syndrome
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebellar infarction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain oedema
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nerve root compression
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    4 / 509 (0.79%)
    4 / 125 (3.20%)
    2 / 124 (1.61%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stupor
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Unresponsive to stimuli
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Exophthalmos
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colonic fistula
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal perforation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal perforation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal polyp
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct obstruction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic lesion
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus bladder
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus ureteric
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus urethral
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    10 / 509 (1.96%)
    3 / 125 (2.40%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obstructive uropathy
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prerenal failure
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    1 / 509 (0.20%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    2 / 509 (0.39%)
    2 / 125 (1.60%)
    2 / 124 (1.61%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    1 / 509 (0.20%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    4 / 509 (0.79%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chondrocalcinosis pyrophosphate
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mobility decreased
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis of jaw
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoporosis
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoporotic fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess jaw
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Enterococcal sepsis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis tuberculous
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ophthalmic herpes zoster
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    5 / 509 (0.98%)
    1 / 125 (0.80%)
    3 / 124 (2.42%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    5 / 509 (0.98%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection enterococcal
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dystrophic calcification
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Enzalutamide 160 mg Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg Placebo+Abiraterone 1000mg+ Prednisone 10mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    473 / 509 (92.93%)
    111 / 125 (88.80%)
    111 / 124 (89.52%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    11 / 509 (2.16%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    15
    1
    1
    Benign urinary tract neoplasm
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Bowen's disease
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Cancer pain
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Choroidal haemangioma
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Fibroma
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Metastases to central nervous system
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Renal neoplasm
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Seborrhoeic keratosis
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Skin cancer
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Skin papilloma
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    6
    0
    0
    Tumour pain
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Flushing
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Deep vein thrombosis
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    3
    1
    1
    Haematoma
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Haemorrhage
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Hot flush
         subjects affected / exposed
    90 / 509 (17.68%)
    6 / 125 (4.80%)
    3 / 124 (2.42%)
         occurrences all number
    100
    7
    3
    Hypotension
         subjects affected / exposed
    9 / 509 (1.77%)
    0 / 125 (0.00%)
    3 / 124 (2.42%)
         occurrences all number
    9
    0
    3
    Lymphoedema
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Orthostatic hypotension
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    4
    0
    0
    Peripheral artery thrombosis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    2
    0
    Phlebitis
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Peripheral coldness
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Thrombosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Phlebitis superficial
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hypertension
         subjects affected / exposed
    43 / 509 (8.45%)
    24 / 125 (19.20%)
    9 / 124 (7.26%)
         occurrences all number
    53
    36
    10
    Surgical and medical procedures
    Cataract operation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Dupuytren's contracture operation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Endodontic procedure
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Glaucoma surgery
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Nasal polypectomy
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Mole excision
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Peripheral nerve decompression
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Pterygium operation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Skin neoplasm excision
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    3
    0
    1
    Tendon sheath incision
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Tooth extraction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    General disorders and administration site conditions
    Abasia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Asthenia
         subjects affected / exposed
    25 / 509 (4.91%)
    5 / 125 (4.00%)
    3 / 124 (2.42%)
         occurrences all number
    38
    5
    4
    Catheter site haemorrhage
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Chest pain
         subjects affected / exposed
    2 / 509 (0.39%)
    4 / 125 (3.20%)
    3 / 124 (2.42%)
         occurrences all number
    2
    4
    3
    Chest discomfort
         subjects affected / exposed
    3 / 509 (0.59%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    3
    2
    0
    Chills
         subjects affected / exposed
    5 / 509 (0.98%)
    1 / 125 (0.80%)
    2 / 124 (1.61%)
         occurrences all number
    5
    1
    2
    Cyst
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Device failure
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    5
    0
    1
    Device occlusion
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Dysplasia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Face oedema
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    0
    1
    1
    Facial pain
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Fatigue
         subjects affected / exposed
    200 / 509 (39.29%)
    17 / 125 (13.60%)
    18 / 124 (14.52%)
         occurrences all number
    284
    24
    20
    Feeling abnormal
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    4
    0
    0
    Feeling drunk
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Feeling hot
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Gait disturbance
         subjects affected / exposed
    7 / 509 (1.38%)
    1 / 125 (0.80%)
    2 / 124 (1.61%)
         occurrences all number
    7
    1
    2
    General physical health deterioration
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    5
    0
    0
    Hunger
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Hyperpyrexia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hypothermia
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Inflammation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Influenza like illness
         subjects affected / exposed
    6 / 509 (1.18%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    11
    1
    1
    Infusion site extravasation
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Injection site swelling
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Irritability
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Local swelling
         subjects affected / exposed
    5 / 509 (0.98%)
    4 / 125 (3.20%)
    0 / 124 (0.00%)
         occurrences all number
    5
    5
    0
    Malaise
         subjects affected / exposed
    5 / 509 (0.98%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    5
    1
    0
    Medical device complication
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    8
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    7 / 509 (1.38%)
    3 / 125 (2.40%)
    2 / 124 (1.61%)
         occurrences all number
    8
    4
    3
    Oedema
         subjects affected / exposed
    3 / 509 (0.59%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    4
    2
    0
    Oedema peripheral
         subjects affected / exposed
    49 / 509 (9.63%)
    7 / 125 (5.60%)
    16 / 124 (12.90%)
         occurrences all number
    51
    8
    18
    Pain
         subjects affected / exposed
    7 / 509 (1.38%)
    6 / 125 (4.80%)
    2 / 124 (1.61%)
         occurrences all number
    8
    6
    2
    Performance status decreased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    11 / 509 (2.16%)
    4 / 125 (3.20%)
    3 / 124 (2.42%)
         occurrences all number
    13
    4
    4
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Drug hypersensitivity
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Hypersensitivity
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hypogammaglobulinaemia
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Milk allergy
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Seasonal allergy
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    4
    0
    1
    Social circumstances
    Physical assault
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Reproductive system and breast disorders
    Balanitis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Breast pain
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Breast tenderness
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Genital rash
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Gynaecomastia
         subjects affected / exposed
    9 / 509 (1.77%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    10
    0
    1
    Pelvic pain
         subjects affected / exposed
    8 / 509 (1.57%)
    2 / 125 (1.60%)
    3 / 124 (2.42%)
         occurrences all number
    8
    2
    3
    Perineal pain
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    2
    0
    1
    Prostatitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Prostatic pain
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Pruritus genital
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Scrotal pain
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Allergic sinusitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Alveolitis
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Atelectasis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Asthma
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Dysphonia
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Cough
         subjects affected / exposed
    27 / 509 (5.30%)
    5 / 125 (4.00%)
    8 / 124 (6.45%)
         occurrences all number
    29
    5
    8
    Dyspnoea
         subjects affected / exposed
    36 / 509 (7.07%)
    5 / 125 (4.00%)
    5 / 124 (4.03%)
         occurrences all number
    43
    5
    8
    Dyspnoea exertional
         subjects affected / exposed
    7 / 509 (1.38%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    8
    1
    0
    Emphysema
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Dyspnoea paroxysmal nocturnal
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Epistaxis
         subjects affected / exposed
    9 / 509 (1.77%)
    3 / 125 (2.40%)
    2 / 124 (1.61%)
         occurrences all number
    9
    3
    3
    Haemoptysis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hiccups
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Interstitial lung disease
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Laryngeal disorder
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Laryngeal erythema
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Laryngeal oedema
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Lung infiltration
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Nasal obstruction
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Nasal congestion
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    4
    0
    0
    Pleural effusion
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    3
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    8 / 509 (1.57%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    8
    1
    1
    Pleuritic pain
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Pneumothorax
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Productive cough
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    3
    0
    1
    Pulmonary embolism
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences all number
    3
    0
    2
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Pulmonary mass
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Respiration abnormal
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Rales
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Respiratory failure
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    2 / 509 (0.39%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    2
    2
    0
    Rhonchi
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Sinus disorder
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Sleep apnoea syndrome
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Sneezing
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Wheezing
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    2
    0
    1
    Psychiatric disorders
    Abnormal dreams
         subjects affected / exposed
    7 / 509 (1.38%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    11
    0
    1
    Agitation
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    3
    1
    0
    Anxiety
         subjects affected / exposed
    16 / 509 (3.14%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    17
    1
    1
    Apathy
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Bruxism
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Confusional state
         subjects affected / exposed
    10 / 509 (1.96%)
    4 / 125 (3.20%)
    1 / 124 (0.81%)
         occurrences all number
    12
    4
    1
    Delirium
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    3
    1
    1
    Depressed mood
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Disorientation
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    4
    0
    0
    Depression
         subjects affected / exposed
    11 / 509 (2.16%)
    1 / 125 (0.80%)
    5 / 124 (4.03%)
         occurrences all number
    11
    1
    5
    Emotional disorder
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Flat affect
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hallucination
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Initial insomnia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Insomnia
         subjects affected / exposed
    37 / 509 (7.27%)
    6 / 125 (4.80%)
    5 / 124 (4.03%)
         occurrences all number
    40
    6
    5
    Mood altered
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Mood swings
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Nightmare
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Stress
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Sleep disorder
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    2
    0
    1
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatic lesion
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatic steatosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatomegaly
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatotoxicity
         subjects affected / exposed
    0 / 509 (0.00%)
    2 / 125 (1.60%)
    2 / 124 (1.61%)
         occurrences all number
    0
    4
    4
    Hyperbilirubinaemia
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    0
    1
    6
    Jaundice
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Non-alcoholic steatohepatitis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Pneumobilia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 509 (0.20%)
    8 / 125 (6.40%)
    6 / 124 (4.84%)
         occurrences all number
    1
    14
    10
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 509 (0.00%)
    4 / 125 (3.20%)
    2 / 124 (1.61%)
         occurrences all number
    0
    6
    2
    Bacterial test positive
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Blood albumin increased
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    2 / 124 (1.61%)
         occurrences all number
    4
    1
    2
    Blood bilirubin increased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Blood calcium decreased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Blood calcium increased
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Blood cholesterol increased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    6 / 509 (1.18%)
    3 / 125 (2.40%)
    2 / 124 (1.61%)
         occurrences all number
    7
    3
    2
    Blood glucose increased
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    5
    1
    0
    Blood iron decreased
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Blood potassium decreased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Blood potassium increased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Blood pressure increased
         subjects affected / exposed
    2 / 509 (0.39%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences all number
    2
    3
    1
    Blood pressure orthostatic decreased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Blood urine present
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Cardiac murmur
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Cardioactive drug level increased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Cystoscopy
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Ejection fraction decreased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    0
    1
    1
    Gamma-glutamyltransferase abnormal
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Haemoglobin decreased
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences all number
    6
    0
    2
    Heart rate increased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Heart rate irregular
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Heart sounds abnormal
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    International normalised ratio increased
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Liver function test abnormal
         subjects affected / exposed
    0 / 509 (0.00%)
    3 / 125 (2.40%)
    1 / 124 (0.81%)
         occurrences all number
    0
    5
    1
    Lymph node palpable
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Norovirus test positive
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Respiratory rate increased
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Transaminases increased
         subjects affected / exposed
    0 / 509 (0.00%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    0
    2
    0
    Troponin increased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Urine output decreased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Vitamin B12 decreased
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    0
    1
    1
    Weight decreased
         subjects affected / exposed
    22 / 509 (4.32%)
    2 / 125 (1.60%)
    3 / 124 (2.42%)
         occurrences all number
    27
    3
    3
    Weight increased
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    White blood cell count decreased
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    White blood cell count increased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Injury, poisoning and procedural complications
    Accident
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Accidental overdose
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Ankle fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Arthropod bite
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Bone contusion
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Chest injury
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Contusion
         subjects affected / exposed
    7 / 509 (1.38%)
    2 / 125 (1.60%)
    3 / 124 (2.42%)
         occurrences all number
    10
    2
    3
    Excoriation
         subjects affected / exposed
    4 / 509 (0.79%)
    1 / 125 (0.80%)
    2 / 124 (1.61%)
         occurrences all number
    4
    1
    3
    Eye contusion
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Face injury
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Fall
         subjects affected / exposed
    45 / 509 (8.84%)
    11 / 125 (8.80%)
    8 / 124 (6.45%)
         occurrences all number
    68
    13
    8
    Femur fracture
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Foreign body in eye
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Fractured coccyx
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Gastroenteritis radiation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hand fracture
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Head injury
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Humerus fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Injection related reaction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Joint injury
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Laceration
         subjects affected / exposed
    9 / 509 (1.77%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences all number
    11
    3
    1
    Ligament sprain
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Limb injury
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Multiple injuries
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Muscle injury
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Muscle strain
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    7
    0
    0
    Overdose
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Pelvic fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Periorbital contusion
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Post procedural haematuria
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Post-traumatic pain
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Procedural hypotension
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Procedural nausea
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Procedural pain
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Procedural vomiting
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Radius fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Rib fracture
         subjects affected / exposed
    4 / 509 (0.79%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    4
    1
    1
    Skeletal injury
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    1
    1
    1
    Skin wound
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Spinal compression fracture
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    3
    1
    1
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Toxicity to various agents
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Traumatic fracture
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    2 / 124 (1.61%)
         occurrences all number
    0
    1
    3
    Urethral injury
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Wound
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    4
    0
    1
    Wound dehiscence
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Wound secretion
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Wrist fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Congenital, familial and genetic disorders
    Phimosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Cardiac disorders
    Aortic valve stenosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Angina pectoris
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    3
    1
    0
    Arrhythmia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    4 / 509 (0.79%)
    3 / 125 (2.40%)
    4 / 124 (3.23%)
         occurrences all number
    4
    3
    4
    Atrial flutter
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    5
    0
    0
    Bradycardia
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    5
    0
    1
    Bundle branch block right
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    1
    1
    1
    Cardiac failure
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Chordae tendinae rupture
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Coronary artery stenosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Diastolic dysfunction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Extrasystoles
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    3
    0
    1
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Mitral valve disease
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Mitral valve prolapse
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Myocardial infarction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Palpitations
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    2
    1
    1
    Right ventricular dysfunction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Sinus bradycardia
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    7 / 509 (1.38%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences all number
    7
    0
    2
    Ventricular extrasystoles
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Amnesia
         subjects affected / exposed
    9 / 509 (1.77%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    9
    0
    0
    Ataxia
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    5
    0
    0
    Balance disorder
         subjects affected / exposed
    8 / 509 (1.57%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    8
    1
    0
    Burning sensation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Cauda equina syndrome
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Cognitive disorder
         subjects affected / exposed
    11 / 509 (2.16%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    18
    1
    0
    Dementia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Dementia Alzheimer's type
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Disturbance in attention
         subjects affected / exposed
    7 / 509 (1.38%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    8
    1
    1
    Dizziness postural
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Dizziness
         subjects affected / exposed
    41 / 509 (8.06%)
    6 / 125 (4.80%)
    4 / 124 (3.23%)
         occurrences all number
    49
    6
    5
    Dysaesthesia
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Dysarthria
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Dysgeusia
         subjects affected / exposed
    24 / 509 (4.72%)
    3 / 125 (2.40%)
    1 / 124 (0.81%)
         occurrences all number
    26
    4
    1
    Dyskinesia
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Head discomfort
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Headache
         subjects affected / exposed
    49 / 509 (9.63%)
    5 / 125 (4.00%)
    2 / 124 (1.61%)
         occurrences all number
    53
    5
    2
    Hemiparesis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperreflexia
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Hypoaesthesia
         subjects affected / exposed
    10 / 509 (1.96%)
    4 / 125 (3.20%)
    3 / 124 (2.42%)
         occurrences all number
    10
    4
    3
    Hypoglossal nerve paralysis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Hypokinesia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Lethargy
         subjects affected / exposed
    34 / 509 (6.68%)
    3 / 125 (2.40%)
    1 / 124 (0.81%)
         occurrences all number
    37
    5
    1
    Loss of consciousness
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Memory impairment
         subjects affected / exposed
    16 / 509 (3.14%)
    2 / 125 (1.60%)
    2 / 124 (1.61%)
         occurrences all number
    19
    2
    2
    Nerve compression
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Migraine
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    3
    1
    0
    Neuralgia
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    6
    0
    1
    Neuropathy peripheral
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    2
    0
    1
    Paraesthesia
         subjects affected / exposed
    21 / 509 (4.13%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    23
    1
    0
    Parkinsonian gait
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Parkinson's disease
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Parosmia
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Poor quality sleep
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Post herpetic neuralgia
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Presyncope
         subjects affected / exposed
    4 / 509 (0.79%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    5
    1
    1
    Radicular pain
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Restless legs syndrome
         subjects affected / exposed
    9 / 509 (1.77%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    9
    0
    1
    Sciatica
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    6
    0
    2
    Somnolence
         subjects affected / exposed
    7 / 509 (1.38%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    7
    1
    1
    Syncope
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    4
    0
    0
    Tension headache
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Tongue paralysis
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Transient ischaemic attack
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Tremor
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences all number
    5
    0
    2
    Trigeminal neuralgia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Seventh nerve paralysis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    2
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    30 / 509 (5.89%)
    5 / 125 (4.00%)
    5 / 124 (4.03%)
         occurrences all number
    36
    10
    7
    Bone marrow failure
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Haemorrhagic anaemia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Leukocytosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Lymphadenopathy
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Lymphopenia
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Pancytopenia
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Pernicious anaemia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    2
    0
    3
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Deafness bilateral
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Deafness neurosensory
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hearing impaired
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Motion sickness
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Tinnitus
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Vertigo
         subjects affected / exposed
    13 / 509 (2.55%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    17
    0
    1
    Vertigo positional
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Eye disorders
    Amaurosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Cataract
         subjects affected / exposed
    6 / 509 (1.18%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    10
    1
    2
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Conjunctivitis
         subjects affected / exposed
    9 / 509 (1.77%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences all number
    10
    2
    1
    Diplopia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Dry eye
         subjects affected / exposed
    5 / 509 (0.98%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    5
    1
    0
    Exophthalmos
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    2
    0
    1
    Eye disorder
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Eye inflammation
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Eye irritation
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Eye pain
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Eyelid margin crusting
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Iritis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Glaucoma
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Lacrimation increased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Macular fibrosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Ocular icterus
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Night blindness
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Optic ischaemic neuropathy
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Retinal artery occlusion
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Photophobia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Strabismus
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Trichiasis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Vision blurred
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    3
    0
    1
    Visual acuity reduced
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Visual impairment
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Vitreous floaters
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Vitreous haemorrhage
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Eye swelling
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    6
    0
    0
    Abdominal distension
         subjects affected / exposed
    8 / 509 (1.57%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    9
    0
    0
    Abdominal pain
         subjects affected / exposed
    14 / 509 (2.75%)
    7 / 125 (5.60%)
    7 / 124 (5.65%)
         occurrences all number
    14
    7
    7
    Abdominal pain lower
         subjects affected / exposed
    5 / 509 (0.98%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences all number
    5
    3
    1
    Abdominal pain upper
         subjects affected / exposed
    19 / 509 (3.73%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences all number
    21
    0
    2
    Anal haemorrhage
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    4
    0
    0
    Apical granuloma
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Barrett's oesophagus
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Breath odour
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Cheilitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Colitis microscopic
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Constipation
         subjects affected / exposed
    78 / 509 (15.32%)
    17 / 125 (13.60%)
    12 / 124 (9.68%)
         occurrences all number
    89
    21
    13
    Dental caries
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    4
    0
    0
    Diarrhoea
         subjects affected / exposed
    66 / 509 (12.97%)
    7 / 125 (5.60%)
    12 / 124 (9.68%)
         occurrences all number
    77
    9
    12
    Diverticulum intestinal
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Dry mouth
         subjects affected / exposed
    4 / 509 (0.79%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences all number
    4
    2
    1
    Dyspepsia
         subjects affected / exposed
    16 / 509 (3.14%)
    3 / 125 (2.40%)
    4 / 124 (3.23%)
         occurrences all number
    19
    3
    4
    Dysphagia
         subjects affected / exposed
    3 / 509 (0.59%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences all number
    3
    2
    1
    Epigastric discomfort
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Erosive oesophagitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Eructation
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Faecal incontinence
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Faecaloma
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Faeces hard
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Flatulence
         subjects affected / exposed
    12 / 509 (2.36%)
    3 / 125 (2.40%)
    1 / 124 (0.81%)
         occurrences all number
    12
    3
    1
    Food poisoning
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Frequent bowel movements
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Gastric mucosa erythema
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Gastric ulcer
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    4
    0
    0
    Gastritis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences all number
    1
    0
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    13 / 509 (2.55%)
    4 / 125 (3.20%)
    5 / 124 (4.03%)
         occurrences all number
    13
    4
    5
    Gingival bleeding
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Gingival inflammation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Gingival pain
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Haematochezia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Haemorrhoids
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    4
    0
    1
    Hiatus hernia
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences all number
    2
    0
    2
    Inguinal hernia
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences all number
    3
    0
    2
    Large intestine polyp
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    3
    0
    1
    Lip dry
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Lip oedema
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Localised intraabdominal fluid collection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Melaena
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Nausea
         subjects affected / exposed
    97 / 509 (19.06%)
    21 / 125 (16.80%)
    11 / 124 (8.87%)
         occurrences all number
    123
    27
    11
    Odynophagia
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Oesophageal pain
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Oesophagitis
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Pancreatic disorder
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Pancreatitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Paraesthesia oral
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Periodontal disease
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Proctalgia
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Rectal haemorrhage
         subjects affected / exposed
    2 / 509 (0.39%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    2
    2
    0
    Retching
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Salivary hypersecretion
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Tongue disorder
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Toothache
         subjects affected / exposed
    7 / 509 (1.38%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    7
    0
    1
    Umbilical hernia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Vomiting
         subjects affected / exposed
    28 / 509 (5.50%)
    7 / 125 (5.60%)
    2 / 124 (1.61%)
         occurrences all number
    32
    9
    3
    Skin and subcutaneous tissue disorders
    Actinic keratosis
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Actinic prurigo
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Alopecia
         subjects affected / exposed
    11 / 509 (2.16%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    11
    0
    0
    Blister
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Cold sweat
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Cutaneous lupus erythematosus
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Decubitus ulcer
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Dermal cyst
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Dermatitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Dermatitis acneiform
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Dermatitis contact
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Diabetic foot
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Dry skin
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences all number
    5
    0
    2
    Eczema
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    5
    0
    0
    Granuloma annulare
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hair growth abnormal
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Haemorrhage subcutaneous
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Hyperhidrosis
         subjects affected / exposed
    11 / 509 (2.16%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    11
    2
    0
    Hypertrichosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Intertrigo
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Miliaria
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Erythema
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    3
    1
    0
    Night sweats
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Nail disorder
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Onychoclasis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Panniculitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Pain of skin
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Penile ulceration
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Petechiae
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Photodermatosis
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Pruritus
         subjects affected / exposed
    8 / 509 (1.57%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    11
    0
    0
    Psoriasis
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Rash
         subjects affected / exposed
    14 / 509 (2.75%)
    6 / 125 (4.80%)
    4 / 124 (3.23%)
         occurrences all number
    20
    7
    4
    Rash macular
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Rash erythematous
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Rash pruritic
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    3
    0
    1
    Rash papular
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Skin lesion
         subjects affected / exposed
    4 / 509 (0.79%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    6
    1
    1
    Skin exfoliation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Skin ulcer
         subjects affected / exposed
    2 / 509 (0.39%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    2
    2
    0
    Sticky skin
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Swelling face
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Urticaria
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Renal and urinary disorders
    Bladder pain
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Bladder dysfunction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Bladder spasm
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Calculus bladder
         subjects affected / exposed
    4 / 509 (0.79%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    4
    1
    0
    Calculus ureteric
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Haematuria
         subjects affected / exposed
    18 / 509 (3.54%)
    6 / 125 (4.80%)
    11 / 124 (8.87%)
         occurrences all number
    31
    6
    14
    Dysuria
         subjects affected / exposed
    12 / 509 (2.36%)
    1 / 125 (0.80%)
    5 / 124 (4.03%)
         occurrences all number
    13
    1
    5
    Haemorrhage urinary tract
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Hydronephrosis
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    3
    3
    1
    Incontinence
         subjects affected / exposed
    7 / 509 (1.38%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences all number
    8
    2
    1
    Lower urinary tract symptoms
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Micturition urgency
         subjects affected / exposed
    6 / 509 (1.18%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    6
    0
    0
    Nephrolithiasis
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Nocturia
         subjects affected / exposed
    18 / 509 (3.54%)
    1 / 125 (0.80%)
    4 / 124 (3.23%)
         occurrences all number
    18
    1
    4
    Pollakiuria
         subjects affected / exposed
    12 / 509 (2.36%)
    2 / 125 (1.60%)
    4 / 124 (3.23%)
         occurrences all number
    12
    2
    4
    Polyuria
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Prerenal failure
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Renal colic
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Renal failure
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Renal impairment
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Strangury
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    2 / 124 (1.61%)
         occurrences all number
    1
    1
    2
    Ureteric obstruction
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Urethral dilatation
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Urethral pain
         subjects affected / exposed
    1 / 509 (0.20%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    1
    2
    0
    Urethral stenosis
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Urethritis noninfective
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    2
    0
    1
    Urge incontinence
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Urinary incontinence
         subjects affected / exposed
    16 / 509 (3.14%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences all number
    16
    2
    1
    Urinary hesitation
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    2
    0
    1
    Urinary retention
         subjects affected / exposed
    8 / 509 (1.57%)
    2 / 125 (1.60%)
    2 / 124 (1.61%)
         occurrences all number
    9
    2
    2
    Urine odour abnormal
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Urinary tract obstruction
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    2
    0
    1
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Cushingoid
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    0
    1
    1
    Goitre
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperthyroidism
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Hypothyroidism
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Thyroid mass
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    74 / 509 (14.54%)
    18 / 125 (14.40%)
    14 / 124 (11.29%)
         occurrences all number
    90
    30
    18
    Arthritis
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Arthropathy
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Back pain
         subjects affected / exposed
    104 / 509 (20.43%)
    25 / 125 (20.00%)
    28 / 124 (22.58%)
         occurrences all number
    133
    32
    33
    Bone fistula
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Bone pain
         subjects affected / exposed
    21 / 509 (4.13%)
    3 / 125 (2.40%)
    4 / 124 (3.23%)
         occurrences all number
    23
    3
    6
    Bursitis
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    3
    0
    1
    Coccydynia
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Flank pain
         subjects affected / exposed
    5 / 509 (0.98%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    5
    2
    0
    Groin pain
         subjects affected / exposed
    12 / 509 (2.36%)
    1 / 125 (0.80%)
    5 / 124 (4.03%)
         occurrences all number
    12
    2
    5
    Inguinal mass
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Joint range of motion decreased
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Joint stiffness
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Joint swelling
         subjects affected / exposed
    4 / 509 (0.79%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences all number
    4
    2
    1
    Mobility decreased
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Muscle atrophy
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Muscle fatigue
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Muscle tightness
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Muscle spasms
         subjects affected / exposed
    7 / 509 (1.38%)
    4 / 125 (3.20%)
    9 / 124 (7.26%)
         occurrences all number
    7
    9
    10
    Muscular weakness
         subjects affected / exposed
    21 / 509 (4.13%)
    6 / 125 (4.80%)
    4 / 124 (3.23%)
         occurrences all number
    26
    6
    7
    Musculoskeletal chest pain
         subjects affected / exposed
    23 / 509 (4.52%)
    13 / 125 (10.40%)
    7 / 124 (5.65%)
         occurrences all number
    26
    17
    9
    Musculoskeletal discomfort
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    33 / 509 (6.48%)
    11 / 125 (8.80%)
    8 / 124 (6.45%)
         occurrences all number
    34
    14
    9
    Myalgia
         subjects affected / exposed
    23 / 509 (4.52%)
    1 / 125 (0.80%)
    2 / 124 (1.61%)
         occurrences all number
    25
    1
    2
    Musculoskeletal stiffness
         subjects affected / exposed
    4 / 509 (0.79%)
    3 / 125 (2.40%)
    0 / 124 (0.00%)
         occurrences all number
    4
    3
    0
    Myopathy
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Myositis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Neck pain
         subjects affected / exposed
    23 / 509 (4.52%)
    2 / 125 (1.60%)
    3 / 124 (2.42%)
         occurrences all number
    26
    3
    3
    Osteoarthritis
         subjects affected / exposed
    6 / 509 (1.18%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    8
    0
    1
    Osteonecrosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Osteonecrosis of jaw
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Osteopenia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Osteoporosis
         subjects affected / exposed
    0 / 509 (0.00%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    0
    2
    0
    Pain in extremity
         subjects affected / exposed
    33 / 509 (6.48%)
    9 / 125 (7.20%)
    6 / 124 (4.84%)
         occurrences all number
    39
    11
    7
    Pain in jaw
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Pathological fracture
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Plantar fasciitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Scoliosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Spinal column stenosis
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Spinal osteoarthritis
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    2
    1
    0
    Spinal pain
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    5
    0
    1
    Synovial cyst
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Synovitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Tendonitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    2
    0
    1
    Trismus
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Abscess
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Abscess neck
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Atypical mycobacterial infection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Bronchitis
         subjects affected / exposed
    4 / 509 (0.79%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    6
    1
    1
    Bronchopneumonia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Carbuncle
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    2
    0
    Catheter site infection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Cellulitis
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Conjunctivitis infective
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Cystitis
         subjects affected / exposed
    4 / 509 (0.79%)
    1 / 125 (0.80%)
    2 / 124 (1.61%)
         occurrences all number
    4
    1
    3
    Diverticulitis
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Ear infection
         subjects affected / exposed
    2 / 509 (0.39%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences all number
    2
    2
    1
    Erysipelas
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Eye infection
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    4
    0
    0
    Eyelid infection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Folliculitis
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    4
    0
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Furuncle
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Gastroenteritis
         subjects affected / exposed
    4 / 509 (0.79%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    5
    1
    0
    Genital candidiasis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Gingival infection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Gingivitis
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Helicobacter infection
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    1
    1
    0
    Herpes simplex
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Herpes zoster
         subjects affected / exposed
    5 / 509 (0.98%)
    4 / 125 (3.20%)
    2 / 124 (1.61%)
         occurrences all number
    5
    4
    2
    Herpes zoster oticus
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Infected cyst
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Infected dermal cyst
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Infection
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    2
    0
    1
    Infection parasitic
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Influenza
         subjects affected / exposed
    20 / 509 (3.93%)
    4 / 125 (3.20%)
    5 / 124 (4.03%)
         occurrences all number
    22
    4
    5
    Injection site infection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Labyrinthitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Laryngitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Lip infection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Lobar pneumonia
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Localised infection
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    3
    1
    0
    Lower respiratory tract infection
         subjects affected / exposed
    16 / 509 (3.14%)
    2 / 125 (1.60%)
    4 / 124 (3.23%)
         occurrences all number
    19
    2
    5
    Lung infection
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Mediastinitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Nail infection
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    31 / 509 (6.09%)
    0 / 125 (0.00%)
    7 / 124 (5.65%)
         occurrences all number
    43
    0
    8
    Onychomycosis
         subjects affected / exposed
    2 / 509 (0.39%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    2
    1
    1
    Oral candidiasis
         subjects affected / exposed
    9 / 509 (1.77%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    9
    1
    1
    Oral herpes
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Otitis media
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Peritonitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Pharyngitis
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Pneumonia
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    3
    1
    0
    Pulpitis dental
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Rash pustular
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    4
    0
    1
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    5
    0
    0
    Scrotal abscess
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Sialoadenitis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Sinusitis
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    3 / 124 (2.42%)
         occurrences all number
    6
    0
    3
    Skin candida
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Soft tissue infection
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Tinea cruris
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Tooth abscess
         subjects affected / exposed
    0 / 509 (0.00%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    0
    2
    0
    Tooth infection
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Tracheitis
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    25 / 509 (4.91%)
    9 / 125 (7.20%)
    5 / 124 (4.03%)
         occurrences all number
    26
    12
    5
    Urethritis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    1
    0
    1
    Urinary tract infection
         subjects affected / exposed
    29 / 509 (5.70%)
    9 / 125 (7.20%)
    6 / 124 (4.84%)
         occurrences all number
    41
    11
    6
    Urosepsis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Viral infection
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    1 / 124 (0.81%)
         occurrences all number
    5
    2
    1
    Metabolism and nutrition disorders
    Abnormal loss of weight
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Decreased appetite
         subjects affected / exposed
    82 / 509 (16.11%)
    13 / 125 (10.40%)
    10 / 124 (8.06%)
         occurrences all number
    97
    15
    10
    Dehydration
         subjects affected / exposed
    4 / 509 (0.79%)
    2 / 125 (1.60%)
    1 / 124 (0.81%)
         occurrences all number
    4
    2
    1
    Diabetes mellitus
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    2 / 124 (1.61%)
         occurrences all number
    1
    0
    2
    Dyslipidaemia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Fluid overload
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Fluid retention
         subjects affected / exposed
    0 / 509 (0.00%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    0
    2
    0
    Gout
         subjects affected / exposed
    0 / 509 (0.00%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    0
    0
    1
    Hypercalcaemia
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    5
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    4
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    8 / 509 (1.57%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    8
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    4 / 509 (0.79%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    6
    0
    0
    Hyperlipidaemia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hypernatraemia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Hypocalcaemia
         subjects affected / exposed
    6 / 509 (1.18%)
    2 / 125 (1.60%)
    0 / 124 (0.00%)
         occurrences all number
    6
    2
    0
    Hypoglycaemia
         subjects affected / exposed
    1 / 509 (0.20%)
    1 / 125 (0.80%)
    3 / 124 (2.42%)
         occurrences all number
    1
    1
    4
    Hypokalaemia
         subjects affected / exposed
    7 / 509 (1.38%)
    9 / 125 (7.20%)
    7 / 124 (5.65%)
         occurrences all number
    8
    11
    9
    Hypomagnesaemia
         subjects affected / exposed
    3 / 509 (0.59%)
    1 / 125 (0.80%)
    2 / 124 (1.61%)
         occurrences all number
    4
    3
    2
    Hyponatraemia
         subjects affected / exposed
    5 / 509 (0.98%)
    0 / 125 (0.00%)
    1 / 124 (0.81%)
         occurrences all number
    6
    0
    5
    Increased appetite
         subjects affected / exposed
    0 / 509 (0.00%)
    1 / 125 (0.80%)
    0 / 124 (0.00%)
         occurrences all number
    0
    1
    0
    Iron deficiency
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Lactic acidosis
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Malnutrition
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    3 / 509 (0.59%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    3
    0
    0
    Vitamin B complex deficiency
         subjects affected / exposed
    1 / 509 (0.20%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    1
    0
    0
    Vitamin B12 deficiency
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0
    Vitamin D deficiency
         subjects affected / exposed
    2 / 509 (0.39%)
    0 / 125 (0.00%)
    0 / 124 (0.00%)
         occurrences all number
    2
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Jun 2014
    The main purpose was to add an exploratory objective to analyze candidate biomarkers in circulation for association with disease response or progression and to evaluate mechanisms of resistance to identify future subjects who may benefit most from these androgen receptor targeting treatment strategies.The purpose was also to define and clarify the requirements for PSA assessments to determine eligibility, the possible outcomes for responders and nonresponders based on the initial PSA assessment at week 13, the timing of unconfirmed and confirmed PSA assessments for the transition from period 1 and period 2, and the new PSA assessment at safety follow-up. there
    07 Jul 2016
    The purpose was to include a second open-label period after randomization closed in period 2 to offer qualifying subjects participating in period 1 the opportunity to continue receiving enzalutamide or to receive abiraterone and prednisone after confirmed PSA progression.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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