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    Clinical Trial Results:
    A Randomized Phase 3 Study Comparing Standard First-Line Docetaxel/Prednisone to Docetaxel/Prednisone in Combination with Custirsen (OGX-011) in Men with Metastatic Castrate Resistant Prostate Cancer

    Summary
    EudraCT number
    		 2010-021011-16
    Trial protocol
    		 HU   FR   DE   ES   BE   NL   GB   IT  
    Global end of trial date
    30 Jun 2014

    Results information
    Results version number
    		 v2(current)
    This version publication date
    10 Apr 2016
    First version publication date
    07 Aug 2015
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • New data added to full data set
    • Correction of full data set
    add back-up user

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    OGX-011-11
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01188187
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Teva: TV-1011/11
    Sponsors
    Sponsor organisation name
    OncoGenex Technologies Inc
    Sponsor organisation address
    1001 W Broadway, Suite 400, Vancouver, BC , Canada, V6H 4B1
    Public contact
    Director, Regulatory Affairs, OncoGenex Pharmaceuticals, Inc, 01 425-686-1500,
    Scientific contact
    Director, Regulatory Affairs, OncoGenex Pharmaceuticals, Inc, 01 425-686-1500,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    24 Apr 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Jun 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To ascertain whether the survival time distribution for patients randomized to the investigational arm is consistent with longer survival as compared to patients randomized to the control arm.
    Protection of trial subjects
    The informed consent forms used for the study comply with the Declaration of Helsinki and its updates and the International Conference on Harmonization (ICH) Guidelines and have been approved by the Sponsor and the Investigator’s IRB/EC/REB. The Investigator explained the nature of the study and the treatment in such a manner that the patient was aware of his/her rights and responsibilities, as well as potential benefits and risks. Patients were informed that participation is voluntary and that they may withdraw from the study at any time, without prejudice to their current or future care. Documentation of the discussion and the date of informed consent was recorded in the patient’s medical record or a study/clinic chart. Patients, or their legally authorized representative, gave informed consent in writing prior to the performance of any protocol-specific procedure.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Nov 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 21
    Country: Number of subjects enrolled
    Spain: 105
    Country: Number of subjects enrolled
    United Kingdom: 70
    Country: Number of subjects enrolled
    Belgium: 17
    Country: Number of subjects enrolled
    France: 133
    Country: Number of subjects enrolled
    Germany: 163
    Country: Number of subjects enrolled
    Hungary: 64
    Country: Number of subjects enrolled
    Italy: 58
    Country: Number of subjects enrolled
    Canada: 167
    Country: Number of subjects enrolled
    Israel: 35
    Country: Number of subjects enrolled
    Korea, Republic of: 41
    Country: Number of subjects enrolled
    United States: 148
    Worldwide total number of subjects
    1022
    EEA total number of subjects
    631
    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)
    305
    From 65 to 84 years
    705
    85 years and over
    12

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 One thousand two hundred seventy patients were screened and 1022 randomized. Stratified randomization was used in order to minimize between-arm imbalance over two stratification factors: use of opioids for prostate cancer-related pain at screening (yes versus no) and radiographic evidence (e.g., CT or bone scan) of progression (yes versus no).

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    A blinding plan for the Sponsor was implemented to minimize the chance of Sponsor decisions being affected by knowledge of the arm assignment of individual patients, knowledge of the results from the secondary outcome, or accumulating survival data. An unblinded independent Data Monitoring Committee, supported by an independent statistician monitored the progress of the study. Once the last patient completed treatment, the Sponsor was no longer blinded.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Docetaxel/prednisone
    Arm description
    		 Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day. Treatment continued for 10 cycles or until unacceptable toxicity or disease progression.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Docetaxel (75 mg/M^2) was administered IV on Day 1 of each 21 day cycle, for up to 10 treatment cycles or until unacceptable toxicity or disease progression.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral prednisone (5 mg twice daily for a total of 10 mg/day) began on Day 1 of Cycle 1 and continued, at a minimum, through the completion of the final treatment cycle.

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dexamethasone 8 mg by mouth twice a day for 3 days beginning one day before docetaxel administration to reduce the incidence and severity of hypersensitivity reactions and fluid retention.

    Arm title
    		 Docetaxel/prednisone/custirsen
    Arm description
    		 Three doses of 640 mg custirsen administered IV as a loading dose between Days -9 to -1. Custirsen, 640 mg, given IV weekly on Days 1, 8, and 15 of each 21 day cycle. Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day. Treatment continued for 10 cycles or until unacceptable toxicity or disease progression .
    Arm type
    		 Experimental

    Investigational medicinal product name
    Custirsen
    Investigational medicinal product code
    Other name
    OGX-011
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Three doses of 640 mg custirsen were administered IV over 2 hours as loading doses during Days -9 to -1. There must have been at least one “non-infusion” day between each administration of custirsen (i.e. every other day) and between the third loading dose of custirsen and Day 1 of Cycle 1. There were no more than 7 days between the last loading dose and Day 1 of Cycle 1. A common schedule was to give the three loading doses of custirsen on Monday, Wednesday and Friday with Day 1, Cycle 1 starting on the following Monday. During study dosing of custirsen consisted of weekly 640 mg intravenous injections on Days 1, 8, and 15 of each 21 day cycle for up to 10 treatment cycles or until unacceptable toxicity or disease progression. Custirsen was administered prior to docetaxel on Day 1 of each cycle.

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Docetaxel (75 mg/M^2) was administered IV on Day 1 of each 21 day cycle, for up to 10 treatment cycles or until unacceptable toxicity or disease progression.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral prednisone (5 mg twice daily for a total of 10 mg/day) began on Day 1 of Cycle 1 and continued, at a minimum, through the completion of the final treatment cycle.

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Dexamethasone 8 mg by mouth twice a day for 3 days beginning one day before docetaxel administration to reduce the incidence and severity of hypersensitivity reactions and fluid retention.

    Number of subjects in period 1
    		Docetaxel/prednisone Docetaxel/prednisone/custirsen
    Started
    512
    510
    Completed
    210
    150
    Not completed
    302
    360
         Adverse event, serious fatal
    3
    1
         Consent withdrawn by subject
    35
    42
         Adverse event, non-fatal
    146
    210
         Symptomatic deterioration
    17
    25
         Progressive disease during loading dose
    -
    1
         Not specified
    8
    5
         Death - patient not treated
    1
    -
         Not specified - patient not treated
    6
    4
         Progressive disease
    78
    68
         Lost to follow-up
    1
    -
         Consent withdrawn by subject - patient not treated
    6
    4
         Treatment delay > 3 weeks
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Docetaxel/prednisone
    Reporting group description
    		 Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day. Treatment continued for 10 cycles or until unacceptable toxicity or disease progression.

    Reporting group title
    Docetaxel/prednisone/custirsen
    Reporting group description
    		 Three doses of 640 mg custirsen administered IV as a loading dose between Days -9 to -1. Custirsen, 640 mg, given IV weekly on Days 1, 8, and 15 of each 21 day cycle. Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day. Treatment continued for 10 cycles or until unacceptable toxicity or disease progression .

    Reporting group values
    		 Docetaxel/prednisone Docetaxel/prednisone/custirsen Total
    Number of subjects
    		 512 510 1022
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 156 149 305
        From 65-84 years
    		 346 359 705
        85 years and over
    		 10 2 12
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 68.3 ( 7.74 ) 68.6 ( 7.75 ) -
    Gender categorical
    Units: Subjects
        Female
    		 0 0 0
        Male
    		 512 510 1022
    Race
    Units: Subjects
        White
    		 461 463 924
        Black or African American
    		 14 9 23
        Asian
    		 24 28 52
        American Indian or Alaska Native
    		 2 0 2
        Native Hawaiian or Pacific Islander
    		 0 0 0
        Hispanic
    		 0 0 0
        Mixed
    		 1 1 2
        Other
    		 5 6 11
        Missing
    		 5 3 8
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 28 23 51
        Non-Hispanic and Non-Latino
    		 480 485 965
        Unknown
    		 0 0 0
        Missing
    		 4 2 6
    Use of Opioids for Prostate-related Cancer Pain
    This was a stratification factor.
    Units: Subjects
        Yes
    		 171 174 345
        No
    		 341 336 677
    Radiographic Evidence of Progression
    This was a stratification factor.
    Units: Subjects
        Yes
    		 404 404 808
        No
    		 108 106 214
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 85.3 ( 16.86 ) 84.9 ( 16.7 ) -
    Height
    Units: cm
        arithmetic mean (standard deviation)
    		 173.5 ( 7.23 ) 173.5 ( 7.69 ) -
    Body Mass Index
    Units: kg/m^2
        arithmetic mean (standard deviation)
    		 28.3 ( 5.06 ) 28.2 ( 4.9 ) -
    Body Surface Area
    Units: m^2
        arithmetic mean (standard deviation)
    		 2 ( 0.22 ) 2 ( 0.22 ) -

    End points

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    End points reporting groups
    Reporting group title
    Docetaxel/prednisone
    Reporting group description
    		 Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day. Treatment continued for 10 cycles or until unacceptable toxicity or disease progression.

    Reporting group title
    Docetaxel/prednisone/custirsen
    Reporting group description
    		 Three doses of 640 mg custirsen administered IV as a loading dose between Days -9 to -1. Custirsen, 640 mg, given IV weekly on Days 1, 8, and 15 of each 21 day cycle. Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day. Treatment continued for 10 cycles or until unacceptable toxicity or disease progression .

    Primary: Kaplan-Meier Estimates for Time to Death (Overall Survival)

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    End point title
    		 Kaplan-Meier Estimates for Time to Death (Overall Survival)
    End point description
    Time from the date of randomization to death from any cause. After stopping treatment, patients were followed every 4 weeks until disease progression and then followed every 12 weeks until death.
    End point type
    Primary
    End point timeframe
    Randomization (approximately Day -12) to longest survival follow-up (Day 971).
    End point values
    		 Docetaxel/prednisone Docetaxel/prednisone/custirsen
    Number of subjects analysed
    512 [1]
    510 [2]
    Units: months
        median (confidence interval 95%)
    22.2 (20.008 to 24.476)
    23.4 (20.961 to 25.791)
    Notes
    [1] - All randomized patients
    [2] - All randomized patients
    Statistical analysis title
    		 Overall Survival Analysis
    Statistical analysis description
    The consequential hazard ratio used in the specific alternative hypothesis for this trial is 0.75. It was assumed that the control arm patients would have an 18-month median survival time. Under exponential assumptions, the median survival time for the investigational arm was expected to be 24 months corresponding to a hazard rate of 0.347 and a two-year survival of 50%.
    Comparison groups
    Docetaxel/prednisone v Docetaxel/prednisone/custirsen
    Number of subjects included in analysis
    1022
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.2067
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.783
         upper limit
    		 1.106
    Notes
    [3] - An analysis of superiority executed as a stratified logrank test stratified by the stratification factors of 1) use of opioids for prostate-related cancer pain and 2) radiographic evidence of progression.

    Secondary: Percentage of Participants Who Were Alive Without Event At Day 140

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    End point title
    		 Percentage of Participants Who Were Alive Without Event At Day 140
    End point description
    Patients who were alive without event (AWE) are patients who had their Milestone Day 140 Disease Status performed per protocol (Day 125 - Day 155 window), were not determined to have disease progression by the investigator on that window and confirmed as not having progressive disease (NON-PD) by the Central Imagine Lab independent review.
    End point type
    Secondary
    End point timeframe
    Day 125-155
    End point values
    		 Docetaxel/prednisone Docetaxel/prednisone/custirsen
    Number of subjects analysed
    512 [4]
    510 [5]
    Units: percentage of participants
        number (not applicable)
    58
    57
    Notes
    [4] - All randomized patients
    [5] - All randomized patients
    Statistical analysis title
    		 AWE Analysis
    Statistical analysis description
    Based on Cochran-Mantel-Haenszel (CMH) Analysis with use of opioids for prostate cancer-related pain at screening (yes versus no) and radiographic evidence of progression (yes versus no) as stratification factors. P-value is not reported (NR) if Odds-Ratio (OR)<1.
    Comparison groups
    Docetaxel/prednisone v Docetaxel/prednisone/custirsen
    Number of subjects included in analysis
    1022
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.236

    Other pre-specified: Percentage of Participants with Adverse Events

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    End point title
    		 Percentage of Participants with Adverse Events
    End point description
    An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the administration, at any dose, of a medicinal or therapeutic product whether or not considered related to that product. Severity was rated by the investigator on a scale of 1 (mild) to 5 (death). A severity of 3 = Severe or medically significant but not immediately life-threatening. A severity of 4 = Life-threatening. Serious AEs include death (death due to progressive disease were not reported as an SAE), a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
    End point type
    Other pre-specified
    End point timeframe
    Docetaxel/prednisone/custirsen arm: Days -9 up to Day 743. Docetaxel/prednisone arm: Day 1 up to Day 400
    End point values
    		 Docetaxel/prednisone Docetaxel/prednisone/custirsen
    Number of subjects analysed
    499 [6]
    501 [7]
    Units: percentage of participants
    number (not applicable)
        Any AE
    97
    100
        Severe AE (grade 3+)
    62
    77
        Serious AE
    36
    43
        Discontinued study early due to AE
    30
    43
    Notes
    [6] - Safety analysis set of participants who received at least one dose of custirsen or docetaxel.
    [7] - Safety analysis set of participants who received at least one dose of custirsen or docetaxel.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Docetaxel/prednisone/custirsen arm: Days -9 up to Day 743. Docetaxel/prednisone arm: Day 1 up to Day 400
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    12.1
    Reporting groups
    Reporting group title
    Docetaxel/prednisone/custirsen
    Reporting group description
    		 Three doses of 640 mg custirsen administered IV as a loading dose between Days -9 to -1. Custirsen, 640 mg, given IV weekly on Days 1, 8, and 15 of each 21 day cycle. Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day. Treatment continued for 10 cycles or until unacceptable toxicity or disease progression.

    Reporting group title
    Docetaxel/prednisone
    Reporting group description
    		 Docetaxel (75 mg/M^2 via intravenous injection) on Day 1 of every 21 days plus prednisone (5 mg tablets taken by mouth) twice each day. Treatment continued for 10 cycles or until unacceptable toxicity or disease progression.

    Serious adverse events
    		 Docetaxel/prednisone/custirsen Docetaxel/prednisone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    214 / 501 (42.71%)
    180 / 499 (36.07%)
         number of deaths (all causes)
    262
    267
         number of deaths resulting from adverse events
    23
    24
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pyogenic granuloma
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroendocrine tumour
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung squamous cell carcinoma stage unspecified
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to meninges
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Phlebitis
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic dissection
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hypotension
         subjects affected / exposed
    5 / 501 (1.00%)
    4 / 499 (0.80%)
         occurrences causally related to treatment / all
    3 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    4 / 501 (0.80%)
    4 / 499 (0.80%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypertension
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Capillary leak syndrome
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Multi-organ failure
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Oedema peripheral
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    1 / 1
    General physical health deterioration
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Infusion related reaction
         subjects affected / exposed
    3 / 501 (0.60%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 501 (0.20%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    16 / 501 (3.19%)
    7 / 499 (1.40%)
         occurrences causally related to treatment / all
    9 / 17
    6 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    9 / 501 (1.80%)
    4 / 499 (0.80%)
         occurrences causally related to treatment / all
    8 / 9
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    5 / 501 (1.00%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    4 / 501 (0.80%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site pain
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Local swelling
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperthermia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion site extravasation
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Epistaxis
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 501 (0.20%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Productive cough
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alveolitis
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    17 / 501 (3.39%)
    16 / 499 (3.21%)
         occurrences causally related to treatment / all
    9 / 17
    4 / 16
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Dyspnoea
         subjects affected / exposed
    5 / 501 (1.00%)
    3 / 499 (0.60%)
         occurrences causally related to treatment / all
    1 / 5
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    4 / 501 (0.80%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary aspiration
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depressed mood
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cyclothymic disorder
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Occult blood positive
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Device occlusion
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    3 / 501 (0.60%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Femur fracture
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Therapeutic agent toxicity
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device malfunction
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    5 / 501 (1.00%)
    4 / 499 (0.80%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stent occlusion
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    2 / 501 (0.40%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Myocardial infarction
         subjects affected / exposed
    2 / 501 (0.40%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Cardiac failure
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Bradycardia
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    2 / 501 (0.40%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Sick sinus syndrome
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Palpitations
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    8 / 501 (1.60%)
    4 / 499 (0.80%)
         occurrences causally related to treatment / all
    4 / 8
    5 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    3 / 501 (0.60%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    3 / 501 (0.60%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 501 (0.20%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    2 / 501 (0.40%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epiduritis
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pachymeningitis
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nerve root compression
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Cerebrovascular accident
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cauda equina syndrome
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    4 / 501 (0.80%)
    4 / 499 (0.80%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensorimotor neuropathy
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraplegia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Grand mal convulsion
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Neuralgic amyotrophy
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia of malignant disease
         subjects affected / exposed
    2 / 501 (0.40%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    38 / 501 (7.58%)
    27 / 499 (5.41%)
         occurrences causally related to treatment / all
    42 / 43
    27 / 28
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    28 / 501 (5.59%)
    28 / 499 (5.61%)
         occurrences causally related to treatment / all
    33 / 33
    30 / 31
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Anaemia
         subjects affected / exposed
    18 / 501 (3.59%)
    12 / 499 (2.40%)
         occurrences causally related to treatment / all
    16 / 22
    13 / 17
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Leukopenia
         subjects affected / exposed
    6 / 501 (1.20%)
    10 / 499 (2.00%)
         occurrences causally related to treatment / all
    5 / 6
    12 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    5 / 501 (1.00%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal tear
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Rectal haemorrhage
         subjects affected / exposed
    3 / 501 (0.60%)
    3 / 499 (0.60%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    2 / 501 (0.40%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    4 / 501 (0.80%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    4 / 5
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    4 / 501 (0.80%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 501 (0.00%)
    3 / 499 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctalgia
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric perforation
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ileus paralytic
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastic ulcer
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer perforation
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    12 / 501 (2.40%)
    9 / 499 (1.80%)
         occurrences causally related to treatment / all
    11 / 12
    8 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    12 / 501 (2.40%)
    3 / 499 (0.60%)
         occurrences causally related to treatment / all
    10 / 12
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    10 / 501 (2.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    4 / 10
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    3 / 501 (0.60%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumatosis intestinalis
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal haemorrhage
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pancreatitis relapsing
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paptic ulcer haemorrhage
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal toxicity
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cholecystitis
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Swelling face
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dry skin
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug eruption
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary tract obstruction
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    2 / 501 (0.40%)
    4 / 499 (0.80%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Urinary retention
         subjects affected / exposed
    2 / 501 (0.40%)
    4 / 499 (0.80%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    2 / 501 (0.40%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage urinary tract
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    3 / 501 (0.60%)
    4 / 499 (0.80%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 4
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    Haematuria
         subjects affected / exposed
    4 / 501 (0.80%)
    3 / 499 (0.60%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vesical fistula
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinoma
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract disorder
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder mass
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Azotaemia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    2 / 501 (0.40%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    3 / 501 (0.60%)
    5 / 499 (1.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    3 / 501 (0.60%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in jaw
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaw disorder
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Urosepsis
         subjects affected / exposed
    3 / 501 (0.60%)
    3 / 499 (0.60%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 3
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    2 / 501 (0.40%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 501 (0.20%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    2 / 501 (0.40%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic infection
         subjects affected / exposed
    2 / 501 (0.40%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    2 / 501 (0.40%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    1 / 1
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Gastroenteritis
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Necrotising fascitis
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Endocarditis
         subjects affected / exposed
    0 / 501 (0.00%)
    2 / 499 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Influenza
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal bacteraemia
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth infection
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal infection
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyonephrosis
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Candida pneumonia
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Campylobacter gastroenteritis
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain abscess
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Arthritis bacterial
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    21 / 501 (4.19%)
    11 / 499 (2.20%)
         occurrences causally related to treatment / all
    15 / 22
    7 / 12
         deaths causally related to treatment / all
    3 / 3
    0 / 0
    Septic shock
         subjects affected / exposed
    9 / 501 (1.80%)
    5 / 499 (1.00%)
         occurrences causally related to treatment / all
    8 / 9
    5 / 5
         deaths causally related to treatment / all
    4 / 5
    3 / 3
    Urinary tract infection
         subjects affected / exposed
    8 / 501 (1.60%)
    5 / 499 (1.00%)
         occurrences causally related to treatment / all
    5 / 10
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    9 / 501 (1.80%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    4 / 9
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Diverticulitis
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site infection
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal osteomyelitis
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia primary atypical
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Infection
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mediastinal abscess
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal abscess
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Administration site abscess
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 501 (0.60%)
    3 / 499 (0.60%)
         occurrences causally related to treatment / all
    6 / 6
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    1 / 501 (0.20%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    4 / 501 (0.80%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypophagia
         subjects affected / exposed
    1 / 501 (0.20%)
    3 / 499 (0.60%)
         occurrences causally related to treatment / all
    1 / 1
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 501 (0.00%)
    1 / 499 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    11 / 501 (2.20%)
    6 / 499 (1.20%)
         occurrences causally related to treatment / all
    9 / 11
    5 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid retention
         subjects affected / exposed
    2 / 501 (0.40%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 501 (0.20%)
    0 / 499 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Docetaxel/prednisone/custirsen Docetaxel/prednisone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    496 / 501 (99.00%)
    476 / 499 (95.39%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    35 / 501 (6.99%)
    32 / 499 (6.41%)
         occurrences all number
    42
    41
    Hypotension
         subjects affected / exposed
    50 / 501 (9.98%)
    15 / 499 (3.01%)
         occurrences all number
    57
    18
    General disorders and administration site conditions
    Mucosal inflammation
         subjects affected / exposed
    64 / 501 (12.77%)
    61 / 499 (12.22%)
         occurrences all number
    92
    89
    Fatigue
         subjects affected / exposed
    241 / 501 (48.10%)
    218 / 499 (43.69%)
         occurrences all number
    688
    611
    Asthenia
         subjects affected / exposed
    172 / 501 (34.33%)
    141 / 499 (28.26%)
         occurrences all number
    393
    300
    Pyrexia
         subjects affected / exposed
    166 / 501 (33.13%)
    68 / 499 (13.63%)
         occurrences all number
    251
    102
    Oedema peripheral
         subjects affected / exposed
    118 / 501 (23.55%)
    94 / 499 (18.84%)
         occurrences all number
    179
    132
    Chills
         subjects affected / exposed
    169 / 501 (33.73%)
    22 / 499 (4.41%)
         occurrences all number
    253
    25
    Pain
         subjects affected / exposed
    44 / 501 (8.78%)
    22 / 499 (4.41%)
         occurrences all number
    55
    26
    Influenza like illness
         subjects affected / exposed
    33 / 501 (6.59%)
    17 / 499 (3.41%)
         occurrences all number
    42
    21
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    109 / 501 (21.76%)
    69 / 499 (13.83%)
         occurrences all number
    157
    92
    Cough
         subjects affected / exposed
    106 / 501 (21.16%)
    70 / 499 (14.03%)
         occurrences all number
    130
    83
    Epistaxis
         subjects affected / exposed
    48 / 501 (9.58%)
    39 / 499 (7.82%)
         occurrences all number
    57
    45
    Oropharyngeal pain
         subjects affected / exposed
    28 / 501 (5.59%)
    18 / 499 (3.61%)
         occurrences all number
    31
    18
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    48 / 501 (9.58%)
    47 / 499 (9.42%)
         occurrences all number
    55
    61
    Investigations
    Weight decreased
         subjects affected / exposed
    80 / 501 (15.97%)
    34 / 499 (6.81%)
         occurrences all number
    117
    48
    Nervous system disorders
    Peripheral sensory neuropathy
         subjects affected / exposed
    59 / 501 (11.78%)
    64 / 499 (12.83%)
         occurrences all number
    86
    120
    Dysgeusia
         subjects affected / exposed
    141 / 501 (28.14%)
    127 / 499 (25.45%)
         occurrences all number
    224
    217
    Neuropathy peripheral
         subjects affected / exposed
    88 / 501 (17.56%)
    90 / 499 (18.04%)
         occurrences all number
    149
    139
    Dizziness
         subjects affected / exposed
    81 / 501 (16.17%)
    67 / 499 (13.43%)
         occurrences all number
    111
    94
    Headache
         subjects affected / exposed
    59 / 501 (11.78%)
    47 / 499 (9.42%)
         occurrences all number
    90
    73
    Paraesthesia
         subjects affected / exposed
    54 / 501 (10.78%)
    50 / 499 (10.02%)
         occurrences all number
    89
    68
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    153 / 501 (30.54%)
    89 / 499 (17.84%)
         occurrences all number
    449
    255
    Anaemia
         subjects affected / exposed
    155 / 501 (30.94%)
    78 / 499 (15.63%)
         occurrences all number
    385
    138
    Leukopenia
         subjects affected / exposed
    52 / 501 (10.38%)
    32 / 499 (6.41%)
         occurrences all number
    170
    91
    Thrombocytopenia
         subjects affected / exposed
    42 / 501 (8.38%)
    10 / 499 (2.00%)
         occurrences all number
    81
    20
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    55 / 501 (10.98%)
    61 / 499 (12.22%)
         occurrences all number
    69
    70
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    271 / 501 (54.09%)
    213 / 499 (42.69%)
         occurrences all number
    614
    452
    Nausea
         subjects affected / exposed
    224 / 501 (44.71%)
    159 / 499 (31.86%)
         occurrences all number
    390
    235
    Constipation
         subjects affected / exposed
    148 / 501 (29.54%)
    94 / 499 (18.84%)
         occurrences all number
    205
    124
    Vomiting
         subjects affected / exposed
    130 / 501 (25.95%)
    71 / 499 (14.23%)
         occurrences all number
    197
    97
    Stomatitis
         subjects affected / exposed
    57 / 501 (11.38%)
    57 / 499 (11.42%)
         occurrences all number
    88
    84
    Dyspepsia
         subjects affected / exposed
    52 / 501 (10.38%)
    46 / 499 (9.22%)
         occurrences all number
    68
    60
    Abdominal pain
         subjects affected / exposed
    52 / 501 (10.38%)
    40 / 499 (8.02%)
         occurrences all number
    66
    44
    Abdominal pain upper
         subjects affected / exposed
    26 / 501 (5.19%)
    21 / 499 (4.21%)
         occurrences all number
    28
    23
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    209 / 501 (41.72%)
    229 / 499 (45.89%)
         occurrences all number
    256
    266
    Nail disorder
         subjects affected / exposed
    77 / 501 (15.37%)
    62 / 499 (12.42%)
         occurrences all number
    94
    73
    Onycholysis
         subjects affected / exposed
    27 / 501 (5.39%)
    39 / 499 (7.82%)
         occurrences all number
    35
    54
    Rash
         subjects affected / exposed
    44 / 501 (8.78%)
    22 / 499 (4.41%)
         occurrences all number
    56
    30
    Dry skin
         subjects affected / exposed
    24 / 501 (4.79%)
    36 / 499 (7.21%)
         occurrences all number
    27
    40
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    28 / 501 (5.59%)
    23 / 499 (4.61%)
         occurrences all number
    34
    27
    Musculoskeletal and connective tissue disorders
    Back pain
    alternative assessment type: Non-systematic
         subjects affected / exposed
    98 / 501 (19.56%)
    85 / 499 (17.03%)
         occurrences all number
    138
    119
    Arthralgia
         subjects affected / exposed
    70 / 501 (13.97%)
    83 / 499 (16.63%)
         occurrences all number
    111
    117
    Pain in extremity
         subjects affected / exposed
    66 / 501 (13.17%)
    80 / 499 (16.03%)
         occurrences all number
    96
    119
    Myalgia
         subjects affected / exposed
    53 / 501 (10.58%)
    49 / 499 (9.82%)
         occurrences all number
    117
    113
    Bone pain
         subjects affected / exposed
    50 / 501 (9.98%)
    45 / 499 (9.02%)
         occurrences all number
    79
    65
    Musculoskeletal pain
         subjects affected / exposed
    48 / 501 (9.58%)
    34 / 499 (6.81%)
         occurrences all number
    62
    48
    Muscle spasms
         subjects affected / exposed
    45 / 501 (8.98%)
    28 / 499 (5.61%)
         occurrences all number
    53
    33
    Muscular weakness
         subjects affected / exposed
    40 / 501 (7.98%)
    30 / 499 (6.01%)
         occurrences all number
    50
    49
    Musculoskeletal chest pain
         subjects affected / exposed
    26 / 501 (5.19%)
    22 / 499 (4.41%)
         occurrences all number
    43
    30
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    54 / 501 (10.78%)
    51 / 499 (10.22%)
         occurrences all number
    68
    61
    Nasopharyngitis
         subjects affected / exposed
    36 / 501 (7.19%)
    34 / 499 (6.81%)
         occurrences all number
    43
    41
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    179 / 501 (35.73%)
    100 / 499 (20.04%)
         occurrences all number
    300
    168
    Dehydration
         subjects affected / exposed
    38 / 501 (7.58%)
    16 / 499 (3.21%)
         occurrences all number
    52
    21
    Hypokalaemia
         subjects affected / exposed
    31 / 501 (6.19%)
    18 / 499 (3.61%)
         occurrences all number
    58
    21
    Hyperglycaemia
         subjects affected / exposed
    30 / 501 (5.99%)
    13 / 499 (2.61%)
         occurrences all number
    77
    40

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Oct 2011
    The significant changes being made are as follows: • Increase the sample size of the study to 1000 patients • Modify the interim analysis to occur at 80% of the required 509 death events • Add evaluation of circulating tumor cells (CTC)

    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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