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    Clinical Trial Results:
    A Randomised, Double-blind, Multicentre Phase II/III Study to Compare the Efficacy of AZD2171 in Combination with 5-fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX), to the Efficacy of Bevacizumab in Combination with FOLFOX in Patients with Previously Untreated Metastatic Colorectal Cancer

    Summary
    EudraCT number
    		 2005-003440-66
    Trial protocol
    		 BE   AT   CZ   DE   SK   HU   IT   GB   FI   LV   MT  
    Global end of trial date
    19 Aug 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Nov 2017
    First version publication date
    08 Nov 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D8480C00013
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    132 Hills Road, Cambridge, United Kingdom, CB2 1PG
    Public contact
    Tsveta Milenkova, AstraZeneca, ClinicalTrialTransparency@astrazeneca.com
    Scientific contact
    Tsveta Milenkova, AstraZeneca, ClinicalTrialTransparency@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Oct 2010
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Nov 2009
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Aug 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This is a phase II/III study to compare the efficacy of AZD2171 in combination with FOLFOX to the efficacy of FOLFOX in combination with bevacizumab
    Protection of trial subjects
    On completion of the phase II part of the study and following review by an Independent Data Monitoring Committee (IDMC), if there is a clear difference between the two doses then the patients from the discontinued dose will be unblinded and given the option to continue treatment on their current dose of AZD2171 or to switch to the dose of AZD2171 selected for the phase III study. If toxicity is encountered, the dose of AZD2171 may be reduced or treatment with AZD2171 and bevacizumab stopped until resolution of symptoms. At the discretion of the investigator, treatment may then be restarted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Aug 2006
    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
    Australia: 243
    Country: Number of subjects enrolled
    Austria: 53
    Country: Number of subjects enrolled
    Belgium: 156
    Country: Number of subjects enrolled
    Canada: 68
    Country: Number of subjects enrolled
    Czech Republic: 120
    Country: Number of subjects enrolled
    Egypt: 28
    Country: Number of subjects enrolled
    Finland: 5
    Country: Number of subjects enrolled
    France: 35
    Country: Number of subjects enrolled
    Germany: 58
    Country: Number of subjects enrolled
    Hungary: 162
    Country: Number of subjects enrolled
    India: 39
    Country: Number of subjects enrolled
    Israel: 28
    Country: Number of subjects enrolled
    Italy: 78
    Country: Number of subjects enrolled
    Latvia: 7
    Country: Number of subjects enrolled
    Malta: 20
    Country: Number of subjects enrolled
    Philippines: 28
    Country: Number of subjects enrolled
    Poland: 51
    Country: Number of subjects enrolled
    Russian Federation: 25
    Country: Number of subjects enrolled
    Slovakia: 21
    Country: Number of subjects enrolled
    South Africa: 23
    Country: Number of subjects enrolled
    Spain: 99
    Country: Number of subjects enrolled
    Taiwan: 9
    Country: Number of subjects enrolled
    Thailand: 15
    Country: Number of subjects enrolled
    Turkey: 11
    Country: Number of subjects enrolled
    United Kingdom: 109
    Country: Number of subjects enrolled
    Ukraine: 270
    Country: Number of subjects enrolled
    United States: 25
    Country: Number of subjects enrolled
    Vietnam: 19
    Worldwide total number of subjects
    1805
    EEA total number of subjects
    974
    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)
    1213
    From 65 to 84 years
    590
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 Phase II patients: 74 (Cediranib 20mg), 76 (Cediranib 30mg), 76 (Bevacizumab 5 mg/kg) Full Analysis Set (ITT) : 709 (Cediranib 20mg), 713 (Bevacizumab 5 mg/kg) Per Protocol Set : 702 (Cediranib 20mg), 696 (Bevacizumab 5 mg/kg) Safety Set (ITT) : 705 (Cediranib 20mg), 704 (Bevacizumab 5 mg/kg)

    Pre-assignment
    Screening details
    		 Cediranib 30 mg discontinued following Phase II, Cediranib 20 mg chosen dose for comparing with Bevacizumab. 1805 patients enrolled to the study, 1614 patients were randomised, and 1600 received randomised treatment.

    Period 1
    Period 1 title
    Overall Study
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cediranib 20 mg
    Arm description
    		 Cediranib 20 mg/day + FOLFOX + bevacizumab placebo
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cediranib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    20 mg orally once daily

    Arm title
    		 Bevacizumab 5 mg/kg
    Arm description
    		 Bevacizumab + FOLFOX + cediranib placebo
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Bevacizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    5mg/kg every 14 days

    Number of subjects in period 1 [1]
    		Cediranib 20 mg Bevacizumab 5 mg/kg
    Started
    709
    713
    Completed
    397
    394
    Not completed
    312
    319
         Consent withdrawn by subject
    52
    48
         Other
    3
    3
         Death
    239
    247
         Incorrect enrolment/eligib not fulfilled
    2
    3
         Lost to follow-up
    16
    18
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The study was a phase 2/3 study and had three arms. Two arms were continued from the phase 2 period into the phase 3 period, and the 30mg arm was dropped. The final analysis was based on the entirety of the data collected for the two arms, therefore due to the structure of pharmaCM we had to enter these two arms into an “overall study” period, and then entered the 30mg arm into a separate study period named “Phase II period (Cediranib 30mg only)”.
    Period 2
    Period 2 title
    Phase II period (Cediranib 30mg only)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Arm title
    		 Cediranib 30 mg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cediranib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    30 mg orally once daily

    Number of subjects in period 2 [2]
    		Cediranib 30 mg
    Started
    192
    Completed
    7
    Not completed
    185
         Adverse event, non-fatal
    55
         Other
    12
         Condition under investigation worsened
    84
         Voluntary discontinuation by patient
    34
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: The number of patients enrolled to a trial isn’t always equal to the number randomised due to things like screening failures. Therefore the numbers randomised to treatment on study in this case are less than the number enrolled.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cediranib 20 mg
    Reporting group description
    		 Cediranib 20 mg/day + FOLFOX + bevacizumab placebo

    Reporting group title
    Bevacizumab 5 mg/kg
    Reporting group description
    		 Bevacizumab + FOLFOX + cediranib placebo

    Reporting group values
    		 Cediranib 20 mg Bevacizumab 5 mg/kg Total
    Number of subjects
    		 709 713 1422
    Age Categorical
    Units: Subjects
        ≥18 to <65 years
    		 501 461 962
        ≥65 to <75 years
    		 166 209 375
        ≥75 years
    		 42 43 85
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58.1 ( 11.37 ) 59 ( 10.82 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 297 299 596
        Male
    		 412 414 826
    Race
    Units: Subjects
        Caucasian
    		 679 666 1345
        Oriental
    		 24 40 64
        Black
    		 4 4 8
        Other
    		 2 3 5
    Ethnic group
    Units: Subjects
        Not applicable
    		 659 646 1305
        Asian
    		 37 53 90
        Chinese
    		 6 5 11
        African
    		 4 1 5
        African-American
    		 1 3 4
        Hispanic
    		 1 2 3
        Other
    		 1 3 4
    BMI
    Units: Kg/m2
        arithmetic mean (standard deviation)
    		 25.56 ( 4.57 ) 25.81 ( 5.15 ) -

    End points

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    End points reporting groups
    Reporting group title
    Cediranib 20 mg
    Reporting group description
    		 Cediranib 20 mg/day + FOLFOX + bevacizumab placebo

    Reporting group title
    Bevacizumab 5 mg/kg
    Reporting group description
    		 Bevacizumab + FOLFOX + cediranib placebo
    Reporting group title
    Cediranib 30 mg
    Reporting group description
    		 -

    Primary: Progression-free survival (PFS)

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    End point title
    		 Progression-free survival (PFS)
    End point description
    The efficacy of cediranib in combination with FOLFOX compared to the efficacy of bevacizumab in combination with FOLFOX by assessment of PFS. For PFS only, non-inferiority, in addition to superiority, of cediranib compared to bevacizumab will also be assessed, as outlined below: • if the hazard ratio is < 1 and the p-value is < 0.05, we will conclude that cediranib provides a statistically significant improvement in PFS compared to bevacizumab alone. • if the upper 2-sided 95% confidence limit for the hazard ratio is <1.2, we will conclude non-inferiority of cediranib compared to bevacizumab with respect to PFS • if the non-inferiority criteria is not reached, and the p-value is > 0.05, we will conclude that there is no statistically significant difference between the treatment groups. • if the hazard ratio is >1, the p-value is <0.05, we will conclude the cediranib is inferior to bevacizumab.
    End point type
    Primary
    End point timeframe
    RECIST assessed at baseline, then at 8 weekly intervals for 24 weeks, and then every 12 weeks thereafter through to progression or data cut off date of 15/11/09 whichever was earliest.
    End point values
    		 Cediranib 20 mg Bevacizumab 5 mg/kg
    Number of subjects analysed
    709
    713
    Units: Months
    median (inter-quartile range (Q1-Q3))
        Median PFS
    9.9 (6.3 to 13.5)
    10.3 (6.5 to 14.1)
    Statistical analysis title
    		 Primary Analysis
    Statistical analysis description
    PFS will be analysed using a log-rank test stratified by performance status (PS, 0 or 1), baseline albumin and baseline ALP, the variables used in the stratified randomisation scheme for the study. Any patient in the study with a baseline performance status of 2 or greater (an important protocol deviation) will be included in the PS 1 category in all formal statistical analysis
    Comparison groups
    Cediranib 20 mg v Bevacizumab 5 mg/kg
    Number of subjects included in analysis
    1422
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.119
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 1.25
    Statistical analysis title
    		 Sensitivity (Alternative censoring mechanism)
    Statistical analysis description
    All progression or death events are included in the analysis, regardless of whether they follow missing, or incomplete RECIST assessments, or if they occur after a patient starts an alternate cancer therapy prior to progression. This analysis uses tumour measurements and assessments provided on the eCRFs.
    Comparison groups
    Cediranib 20 mg v Bevacizumab 5 mg/kg
    Number of subjects included in analysis
    1422
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0925
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.25
    Statistical analysis title
    		 Sensitivity (Interval censored approach)
    Statistical analysis description
    The proportion of patients progressing was compared in discrete time intervals after randomisation. The analysis uses a binary model with a complementary log-log link function so that the results could be approximated as a HR. An adjusted analysis was be performed allowing for the effect of treatment and the same covariates used for the primary analysis. Treatment comparisons was be summarised using the estimated HR from the adjusted binary analysis together with its 95% CI.
    Comparison groups
    Cediranib 20 mg v Bevacizumab 5 mg/kg
    Number of subjects included in analysis
    1422
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0912 [1]
    Method
    		 Binary model
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.27
    Notes
    [1] - Method: Binary model with complementary log-log link function
    Statistical analysis title
    		 Sensitivity (Central review)
    Statistical analysis description
    A supportive analysis was performed using the tumour assessment data provided by an independent central review. When calculating PFS, the progression date is the date determined by the central review, based upon the visit responses provided by the central review, and following programmatic incorporation of the same censoring mechanism as applied to the primary PFS analysis. The date of progression is assumed as the earliest tumour assessment date associated with that visit.
    Comparison groups
    Cediranib 20 mg v Bevacizumab 5 mg/kg
    Number of subjects included in analysis
    1422
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.5641
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 1.2

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    Number of months from randomisation to the date of death from any cause
    End point type
    Secondary
    End point timeframe
    Baseline through to date of death
    End point values
    		 Cediranib 20 mg Bevacizumab 5 mg/kg
    Number of subjects analysed
    709
    713
    Units: Months
        median (inter-quartile range (Q1-Q3))
    22.8 (13.3 to 32.3)
    21.3 (12.2 to 32.8)
    Statistical analysis title
    		 Overall survival
    Statistical analysis description
    The log-rank test was stratified by albumin, ALP, and permance status.
    Comparison groups
    Cediranib 20 mg v Bevacizumab 5 mg/kg
    Number of subjects included in analysis
    1422
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.5459
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.12

    Secondary: Quality of Life (QoL) Questionnaires

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    End point title
    		 Quality of Life (QoL) Questionnaires
    End point description
    End point type
    Secondary
    End point timeframe
    Till data-cut off
    End point values
    		 Cediranib 20 mg Bevacizumab 5 mg/kg
    Number of subjects analysed
    709
    713
    Units: Days
        median (inter-quartile range (Q1-Q3))
    170 (56 to 328)
    245 (112 to 348)
    Statistical analysis title
    		 Time to worsening (FCSI 9-item)
    Statistical analysis description
    Uses same methodology as PFS analysis.
    Comparison groups
    Cediranib 20 mg v Bevacizumab 5 mg/kg
    Number of subjects included in analysis
    1422
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.2
         upper limit
    		 1.56
    Statistical analysis title
    		 Time to worsening (FCSI 7-item)
    Statistical analysis description
    Uses same methodology as PFS analysis.
    Comparison groups
    Cediranib 20 mg v Bevacizumab 5 mg/kg
    Number of subjects included in analysis
    1422
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.26
         upper limit
    		 1.65

    Secondary: Overall Response Rate (ORR)

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    End point title
    		 Overall Response Rate (ORR)
    End point description
    End point type
    Secondary
    End point timeframe
    RECIST assessed at baseline, then at 8 weekly intervals for 24 weeks, and then every 12 weeks thereafter through to progression or data cut off date of 15/11/09 whichever was earliest.
    End point values
    		 Cediranib 20 mg Bevacizumab 5 mg/kg
    Number of subjects analysed
    709
    713
    Units: Responses
        Responders
    328
    337
        Stable disease
    259
    268
        Progressive disease
    82
    79
        Non-evaluable
    40
    29
    Statistical analysis title
    		 Best Objective Response (ORR)
    Statistical analysis description
    An Odds Ratio of greater than 1 favours cediranib. Odds ratio, p-value and confidence interval estimated from a logistic regression model including factors for treatment, Baseline Albumin (<4 and >= 4 g/dl), ALP (<= 160 and >160 u/L) & WHO Performance status (0 or 1/2). For baseline albumin, ALP and WHO performance status, if a baseline value is not available, the strata from the IVRS randomization was assumed
    Comparison groups
    Cediranib 20 mg v Bevacizumab 5 mg/kg
    Number of subjects included in analysis
    1422
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.6719
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.18

    Secondary: Duration of Response (DoR)

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    End point title
    		 Duration of Response (DoR)
    End point description
    End point type
    Secondary
    End point timeframe
    RECIST assessed at baseline, week 1, 2, 4, 6, 8, 12 and then every 4 weeks thereafter through to progression or data cut off date of 15/11/09 whichever was earliest.
    End point values
    		 Cediranib 20 mg Bevacizumab 5 mg/kg
    Number of subjects analysed
    709
    713
    Units: Months
        median (inter-quartile range (Q1-Q3))
    8.6 (6.1 to 12.1)
    9.6 (6.5 to 13.6)
    Statistical analysis title
    		 Duration of response (EDoR)
    Statistical analysis description
    To provide a more robust assessment of duration of response the Expected Duration of Response (EDoR) was analysed. This method combines information of the response rate, based on the entire ITT population, with information based on the duration of response in responding patients, through a simple mixture distribution to calculate the expected duration of response
    Comparison groups
    Cediranib 20 mg v Bevacizumab 5 mg/kg
    Number of subjects included in analysis
    1422
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.2021
    Method
    		 EDoR (Ellis et al 2008)
    Parameter type
    		 Ratio of EDoR
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 1.05

    Secondary: Rate of resection of liver metastases

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    End point title
    		 Rate of resection of liver metastases
    End point description
    The rate of resection will be analyzed using logistic regression, adjusting for the same baseline covariates as PFS, with the addition of a factor for liver only involvement at baseline (patients with only liver involvement at baseline will be assigned a value of 1, while patients with liver involvement and at least one other site of disease will be assigned a value of 0).
    End point type
    Secondary
    End point timeframe
    Till data-cut off
    End point values
    		 Cediranib 20 mg Bevacizumab 5 mg/kg
    Number of subjects analysed
    709
    713
    Units: Patient (n)
        Patients undergoing liver resection
    31
    37
    Statistical analysis title
    		 Rate of resection (odds ratio)
    Statistical analysis description
    The rate of resection will be analyzed using logistic regression, adjusting for the same baseline covariates as PFS, with the addition of a factor for liver only involvement at baseline (patients with only liver involvement at baseline will be assigned a value of 1, while patients with liver involvement and at least one other site of disease will be assigned a value of 0).
    Comparison groups
    Cediranib 20 mg v Bevacizumab 5 mg/kg
    Number of subjects included in analysis
    1422
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 < 0.6368
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.46
    Notes
    [2] - An Odds Ratio of greater than 1 favours cediranib. Subset of patients undergoing liver resection.
    Statistical analysis title
    		 Rate of resection (odds ratio)
    Statistical analysis description
    The rate of resection will be analyzed using logistic regression, adjusting for the same baseline covariates as PFS, with the addition of a factor for liver only involvement at baseline (patients with only liver involvement at baseline will be assigned a value of 1, while patients with liver involvement and at least one other site of disease will be assigned a value of 0).
    Comparison groups
    Cediranib 20 mg v Bevacizumab 5 mg/kg
    Number of subjects included in analysis
    1422
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 < 0.2133
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 3.39
    Notes
    [3] - An Odds Ratio of greater than 1 favours cediranib. Subset of patients undergoing liver resection with no remaining sites of disease on RECIST scan following resection.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until last study visit
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17
    Reporting groups
    Reporting group title
    FOLFOX + bevacizumab 5mg/kg
    Reporting group description
    		 -

    Reporting group title
    FOLFOX + cediranib 20mg
    Reporting group description
    		 -

    Reporting group title
    FOLFOX + cediranib 30mg
    Reporting group description
    		 -

    Serious adverse events
    		 FOLFOX + bevacizumab 5mg/kg FOLFOX + cediranib 20mg FOLFOX + cediranib 30mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    231 / 704 (32.81%)
    275 / 705 (39.01%)
    90 / 192 (46.88%)
         number of deaths (all causes)
    246
    238
    105
         number of deaths resulting from adverse events
    13
    9
    2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    METASTATIC PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOMA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TUMOUR HAEMORRHAGE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TUMOUR PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    ARTERIAL THROMBOSIS LIMB
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CIRCULATORY COLLAPSE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEEP VEIN THROMBOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    9 / 704 (1.28%)
    9 / 705 (1.28%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    8 / 9
    6 / 10
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EMBOLISM VENOUS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMATOMA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    9 / 705 (1.28%)
    4 / 192 (2.08%)
         occurrences causally related to treatment / all
    2 / 2
    10 / 10
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSIVE CRISIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    2 / 705 (0.28%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOTENSION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    JUGULAR VEIN THROMBOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    3 / 705 (0.43%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ORTHOSTATIC HYPOTENSION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SHOCK HAEMORRHAGIC
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUBCLAVIAN VEIN THROMBOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THROMBOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VASOSPASM
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VENA CAVA THROMBOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VENOUS THROMBOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VENOUS THROMBOSIS LIMB
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    3 / 705 (0.43%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CATHETER RELATED COMPLICATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CATHETER THROMBOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHILLS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEATH
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    FATIGUE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    6 / 705 (0.85%)
    7 / 192 (3.65%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 7
    5 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    INFUSION SITE EXTRAVASATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFUSION SITE INFLAMMATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MALAISE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    3 / 705 (0.43%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUCOSAL INFLAMMATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MULTI-ORGAN FAILURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    NON-CARDIAC CHEST PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    3 / 705 (0.43%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OEDEMA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OEDEMA PERIPHERAL
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    11 / 704 (1.56%)
    21 / 705 (2.98%)
    9 / 192 (4.69%)
         occurrences causally related to treatment / all
    6 / 14
    13 / 26
    3 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUDDEN DEATH
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Immune system disorders
    DRUG HYPERSENSITIVITY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    5 / 704 (0.71%)
    2 / 705 (0.28%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    5 / 5
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FOOD ALLERGY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERSENSITIVITY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    FEMALE GENITAL TRACT FISTULA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FIBROCYSTIC BREAST DISEASE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    BRONCHOSPASM
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    DYSPNOEA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    4 / 704 (0.57%)
    3 / 705 (0.43%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    0 / 4
    3 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    EPISTAXIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMOPTYSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARYNGOSPASM
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUNG DISORDER
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    ORGANISING PNEUMONIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PHARYNGEAL OEDEMA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PLEURAL EFFUSION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    PNEUMOTHORAX
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    3 / 704 (0.43%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    21 / 704 (2.98%)
    13 / 705 (1.84%)
    6 / 192 (3.13%)
         occurrences causally related to treatment / all
    16 / 21
    11 / 15
    5 / 6
         deaths causally related to treatment / all
    2 / 4
    0 / 0
    0 / 0
    Psychiatric disorders
    BRADYPHRENIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEPRESSION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DISSOCIATIVE DISORDER
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUICIDAL IDEATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ASPARTATE AMINOTRANSFERASE INCREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BLOOD PRESSURE INCREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BODY TEMPERATURE INCREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    C-REACTIVE PROTEIN INCREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ELECTROCARDIOGRAM QT PROLONGED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GAMMA-GLUTAMYLTRANSFERASE INCREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GLOMERULAR FILTRATION RATE DECREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMOGLOBIN DECREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LIPASE INCREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRANSAMINASES INCREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VIRAL TEST POSITIVE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WEIGHT DECREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    ABDOMINAL WOUND DEHISCENCE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CARDIAC VALVE REPLACEMENT COMPLICATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    DRUG TOXICITY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FEMUR FRACTURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL STOMA COMPLICATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HIP FRACTURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    JOINT DISLOCATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUMBAR VERTEBRAL FRACTURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MULTIPLE FRACTURES
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PATELLA FRACTURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POST PROCEDURAL COMPLICATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    3 / 705 (0.43%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    POST PROCEDURAL HAEMORRHAGE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROCEDURAL PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND DEHISCENCE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WRIST FRACTURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE MYOCARDIAL INFARCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    3 / 704 (0.43%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    ANGINA PECTORIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANGINA UNSTABLE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARRHYTHMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ARTERIOSPASM CORONARY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIAL FLUTTER
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIAL THROMBOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ATRIOVENTRICULAR BLOCK
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRADYCARDIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CARDIAC FAILURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    3 / 705 (0.43%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 2
    0 / 0
    CARDIOMYOPATHY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CARDIOPULMONARY FAILURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    CORONARY ARTERY DISEASE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTRACARDIAC THROMBUS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LEFT VENTRICULAR DYSFUNCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LEFT VENTRICULAR FAILURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    MITRAL VALVE INCOMPETENCE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYOCARDIAL ISCHAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    3 / 705 (0.43%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERICARDITIS CONSTRICTIVE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUPRAVENTRICULAR TACHYCARDIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    APHASIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL HAEMORRHAGE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    3 / 705 (0.43%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    2 / 2
    2 / 2
    CEREBRAL INFARCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL ISCHAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CEREBROVASCULAR ACCIDENT
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COGNITIVE DISORDER
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CONVULSION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEPRESSED LEVEL OF CONSCIOUSNESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIZZINESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FACIAL PALSY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GRAND MAL CONVULSION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHAGIC CEREBRAL INFARCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMORRHAGIC STROKE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEADACHE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEMIPARESIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSIVE ENCEPHALOPATHY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ISCHAEMIC CEREBRAL INFARCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LETHARGY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LOSS OF CONSCIOUSNESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NERVE ROOT LESION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUROPATHY PERIPHERAL
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PARTIAL SEIZURES
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERONEAL NERVE PALSY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SOMNOLENCE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SYNCOPE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    3 / 705 (0.43%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TOXIC ENCEPHALOPATHY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    3 / 705 (0.43%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VASCULAR ENCEPHALOPATHY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    AGRANULOCYTOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    3 / 704 (0.43%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COAGULOPATHY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DISSEMINATED INTRAVASCULAR COAGULATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FEBRILE NEUTROPENIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    13 / 704 (1.85%)
    11 / 705 (1.56%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    17 / 17
    14 / 15
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    IDIOPATHIC THROMBOCYTOPENIC PURPURA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LEUKOPENIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    11 / 704 (1.56%)
    8 / 705 (1.13%)
    5 / 192 (2.60%)
         occurrences causally related to treatment / all
    10 / 11
    7 / 8
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCYTOPENIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    THROMBOCYTOPENIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    6 / 705 (0.85%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    1 / 1
    6 / 6
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    DEAFNESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VERTIGO
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    DIPLOPIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ULCERATIVE KERATITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    10 / 704 (1.42%)
    9 / 705 (1.28%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    3 / 10
    1 / 9
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL PAIN LOWER
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL PAIN UPPER
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    3 / 704 (0.43%)
    2 / 705 (0.28%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANAL FISSURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANAL FISTULA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    4 / 704 (0.57%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ASCITES
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    3 / 704 (0.43%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COLONIC OBSTRUCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CONSTIPATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    4 / 704 (0.57%)
    3 / 705 (0.43%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    1 / 4
    2 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    13 / 704 (1.85%)
    30 / 705 (4.26%)
    11 / 192 (5.73%)
         occurrences causally related to treatment / all
    13 / 15
    32 / 35
    11 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DUODENAL ULCER
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DUODENAL ULCER PERFORATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DUODENITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTERITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTEROVESICAL FISTULA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRIC ULCER HAEMORRHAGE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTRITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL HAEMORRHAGE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL INFLAMMATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL TOXICITY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROOESOPHAGEAL REFLUX DISEASE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ILEUS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    6 / 704 (0.85%)
    7 / 705 (0.99%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    0 / 6
    2 / 7
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    ILEUS PARALYTIC
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INGUINAL HERNIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL HAEMORRHAGE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    12 / 704 (1.70%)
    9 / 705 (1.28%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    3 / 12
    3 / 9
    1 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    INTESTINAL PERFORATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    6 / 704 (0.85%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    3 / 6
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINAL HAEMORRHAGE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINAL OBSTRUCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE PERFORATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MELAENA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MESENTERIC ARTERY THROMBOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    MOUTH ULCERATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NAUSEA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    4 / 704 (0.57%)
    10 / 705 (1.42%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    4 / 4
    9 / 10
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL VARICES HAEMORRHAGE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    OESOPHAGITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS ACUTE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIPROCTITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERITONITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PROCTALGIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RECTAL HAEMORRHAGE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    5 / 705 (0.71%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 6
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    RECTAL PERFORATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    REFLUX OESOPHAGITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    7 / 704 (0.99%)
    7 / 705 (0.99%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    2 / 7
    2 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STOMATITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    7 / 705 (0.99%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    1 / 1
    8 / 8
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUBILEUS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    3 / 705 (0.43%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VARICES OESOPHAGEAL
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VOMITING
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    12 / 704 (1.70%)
    11 / 705 (1.56%)
    3 / 192 (1.56%)
         occurrences causally related to treatment / all
    10 / 12
    10 / 11
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    BILE DUCT OBSTRUCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    CHOLECYSTITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATIC FAILURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    HEPATIC PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERBILIRUBINAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PORTAL VEIN THROMBOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    DERMATITIS CONTACT
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SUBCUTANEOUS EMPHYSEMA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SWELLING FACE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    BLADDER OBSTRUCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HAEMATURIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYDRONEPHROSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL COLIC
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL FAILURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    2 / 705 (0.28%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL FAILURE ACUTE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RENAL PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URETERIC OBSTRUCTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY INCONTINENCE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY RETENTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    ADRENAL INSUFFICIENCY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    HYPOTHYROIDISM
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    BACK PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    3 / 704 (0.43%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CHONDROCALCINOSIS PYROPHOSPHATE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FLANK PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INTERVERTEBRAL DISC PROTRUSION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUSCULOSKELETAL PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MYALGIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NECK PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    OSTEOPOROSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PAIN IN EXTREMITY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PATHOLOGICAL FRACTURE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIOSTITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    ABDOMINAL ABSCESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL SEPSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    ABSCESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ANAL ABSCESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    APPENDICITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BREAST ABSCESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRONCHITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    BRONCHOPNEUMONIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CATHETER RELATED INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    6 / 704 (0.85%)
    6 / 705 (0.85%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    2 / 6
    2 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CATHETER SEPSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    3 / 704 (0.43%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CATHETER SITE CELLULITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CELLULITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CENTRAL LINE INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    4 / 704 (0.57%)
    4 / 705 (0.57%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    3 / 4
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIAL INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    CYSTITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENDOCARDITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ENTEROCOCCAL INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GAS GANGRENE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    GASTROENTERITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS VIRAL
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GINGIVAL INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HEPATITIS C
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HERPES VIRUS INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HERPES ZOSTER
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    4 / 705 (0.57%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFLUENZA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    INFUSION SITE INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LIVER ABSCESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LOBAR PNEUMONIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    3 / 704 (0.43%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    LUNG INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    MUCORMYCOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    NASOPHARYNGITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    NECROTISING FASCIITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    NEUTROPENIC SEPSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    OESOPHAGEAL CANDIDIASIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PELVIC ABSCESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PERIRECTAL ABSCESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    5 / 704 (0.71%)
    10 / 705 (1.42%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    2 / 5
    6 / 10
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    PULMONARY TUBERCULOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PYELONEPHRITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY TRACT INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    RETROPERITONEAL ABSCESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    SEPSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    6 / 704 (0.85%)
    6 / 705 (0.85%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    1 / 6
    4 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    SEPTIC SHOCK
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    SINUSITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    STAPHYLOCOCCAL INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    2 / 704 (0.28%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    TOOTH ABSCESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UPPER RESPIRATORY TRACT INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    3 / 704 (0.43%)
    6 / 705 (0.85%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 4
    2 / 6
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    UROSEPSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    VIRAL DIARRHOEA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VIRAL INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    WOUND INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DECREASED APPETITE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    2 / 705 (0.28%)
    2 / 192 (1.04%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    DEHYDRATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    8 / 704 (1.14%)
    6 / 705 (0.85%)
    5 / 192 (2.60%)
         occurrences causally related to treatment / all
    7 / 8
    4 / 7
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ELECTROLYTE IMBALANCE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    FLUID INTAKE REDUCED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    GOUT
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERCALCAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    0 / 705 (0.00%)
    1 / 192 (0.52%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERGLYCAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    3 / 704 (0.43%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPERKALAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOALBUMINAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOCALCAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOGLYCAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    1 / 705 (0.14%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPOKALAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    4 / 705 (0.57%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    HYPONATRAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    0 / 704 (0.00%)
    2 / 705 (0.28%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    KETOACIDOSIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    1 / 704 (0.14%)
    0 / 705 (0.00%)
    0 / 192 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 FOLFOX + bevacizumab 5mg/kg FOLFOX + cediranib 20mg FOLFOX + cediranib 30mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    672 / 704 (95.45%)
    684 / 705 (97.02%)
    187 / 192 (97.40%)
    Vascular disorders
    HYPERTENSION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    183 / 704 (25.99%)
    292 / 705 (41.42%)
    92 / 192 (47.92%)
         occurrences all number
    246
    382
    134
    PHLEBITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    31 / 704 (4.40%)
    22 / 705 (3.12%)
    10 / 192 (5.21%)
         occurrences all number
    35
    23
    10
    General disorders and administration site conditions
    ASTHENIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    73 / 704 (10.37%)
    96 / 705 (13.62%)
    31 / 192 (16.15%)
         occurrences all number
    161
    175
    66
    FATIGUE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    299 / 704 (42.47%)
    314 / 705 (44.54%)
    89 / 192 (46.35%)
         occurrences all number
    493
    645
    144
    OEDEMA PERIPHERAL
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    39 / 704 (5.54%)
    28 / 705 (3.97%)
    14 / 192 (7.29%)
         occurrences all number
    49
    33
    15
    PYREXIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    123 / 704 (17.47%)
    92 / 705 (13.05%)
    26 / 192 (13.54%)
         occurrences all number
    174
    128
    43
    Immune system disorders
    DRUG HYPERSENSITIVITY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    50 / 704 (7.10%)
    41 / 705 (5.82%)
    10 / 192 (5.21%)
         occurrences all number
    75
    54
    16
    Respiratory, thoracic and mediastinal disorders
    COUGH
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    68 / 704 (9.66%)
    71 / 705 (10.07%)
    22 / 192 (11.46%)
         occurrences all number
    81
    80
    27
    DYSPHONIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    81 / 704 (11.51%)
    124 / 705 (17.59%)
    47 / 192 (24.48%)
         occurrences all number
    105
    164
    68
    DYSPNOEA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    43 / 704 (6.11%)
    60 / 705 (8.51%)
    27 / 192 (14.06%)
         occurrences all number
    53
    76
    36
    EPISTAXIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    172 / 704 (24.43%)
    169 / 705 (23.97%)
    45 / 192 (23.44%)
         occurrences all number
    261
    224
    71
    OROPHARYNGEAL PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    37 / 704 (5.26%)
    44 / 705 (6.24%)
    13 / 192 (6.77%)
         occurrences all number
    46
    47
    14
    Psychiatric disorders
    DEPRESSION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    23 / 704 (3.27%)
    23 / 705 (3.26%)
    11 / 192 (5.73%)
         occurrences all number
    23
    24
    11
    INSOMNIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    55 / 704 (7.81%)
    49 / 705 (6.95%)
    16 / 192 (8.33%)
         occurrences all number
    64
    55
    17
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    13 / 704 (1.85%)
    18 / 705 (2.55%)
    11 / 192 (5.73%)
         occurrences all number
    16
    25
    14
    WEIGHT DECREASED
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    56 / 704 (7.95%)
    80 / 705 (11.35%)
    32 / 192 (16.67%)
         occurrences all number
    59
    83
    35
    Nervous system disorders
    DIZZINESS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    33 / 704 (4.69%)
    51 / 705 (7.23%)
    16 / 192 (8.33%)
         occurrences all number
    34
    65
    21
    DYSGEUSIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    84 / 704 (11.93%)
    82 / 705 (11.63%)
    24 / 192 (12.50%)
         occurrences all number
    106
    109
    35
    HEADACHE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    90 / 704 (12.78%)
    117 / 705 (16.60%)
    46 / 192 (23.96%)
         occurrences all number
    179
    182
    68
    LETHARGY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    30 / 704 (4.26%)
    40 / 705 (5.67%)
    12 / 192 (6.25%)
         occurrences all number
    49
    59
    20
    NEUROPATHY PERIPHERAL
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    212 / 704 (30.11%)
    218 / 705 (30.92%)
    49 / 192 (25.52%)
         occurrences all number
    337
    433
    68
    PARAESTHESIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    158 / 704 (22.44%)
    157 / 705 (22.27%)
    46 / 192 (23.96%)
         occurrences all number
    319
    301
    101
    PERIPHERAL SENSORY NEUROPATHY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    144 / 704 (20.45%)
    135 / 705 (19.15%)
    37 / 192 (19.27%)
         occurrences all number
    245
    224
    58
    Blood and lymphatic system disorders
    ANAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    79 / 704 (11.22%)
    50 / 705 (7.09%)
    16 / 192 (8.33%)
         occurrences all number
    93
    67
    19
    LEUKOPENIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    52 / 704 (7.39%)
    56 / 705 (7.94%)
    20 / 192 (10.42%)
         occurrences all number
    88
    102
    30
    NEUTROPENIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    228 / 704 (32.39%)
    302 / 705 (42.84%)
    85 / 192 (44.27%)
         occurrences all number
    516
    674
    167
    THROMBOCYTOPENIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    85 / 704 (12.07%)
    186 / 705 (26.38%)
    55 / 192 (28.65%)
         occurrences all number
    150
    325
    104
    Gastrointestinal disorders
    ABDOMINAL PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    124 / 704 (17.61%)
    161 / 705 (22.84%)
    49 / 192 (25.52%)
         occurrences all number
    157
    217
    77
    ABDOMINAL PAIN UPPER
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    59 / 704 (8.38%)
    82 / 705 (11.63%)
    21 / 192 (10.94%)
         occurrences all number
    81
    109
    27
    CONSTIPATION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    187 / 704 (26.56%)
    145 / 705 (20.57%)
    34 / 192 (17.71%)
         occurrences all number
    265
    256
    64
    DIARRHOEA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    354 / 704 (50.28%)
    486 / 705 (68.94%)
    147 / 192 (76.56%)
         occurrences all number
    817
    1541
    475
    DRY MOUTH
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    30 / 704 (4.26%)
    33 / 705 (4.68%)
    10 / 192 (5.21%)
         occurrences all number
    37
    39
    12
    DYSPEPSIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    56 / 704 (7.95%)
    45 / 705 (6.38%)
    11 / 192 (5.73%)
         occurrences all number
    81
    60
    14
    DYSPHAGIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    10 / 704 (1.42%)
    22 / 705 (3.12%)
    11 / 192 (5.73%)
         occurrences all number
    13
    25
    11
    NAUSEA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    349 / 704 (49.57%)
    355 / 705 (50.35%)
    100 / 192 (52.08%)
         occurrences all number
    883
    888
    199
    STOMATITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    187 / 704 (26.56%)
    252 / 705 (35.74%)
    77 / 192 (40.10%)
         occurrences all number
    332
    369
    145
    VOMITING
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    192 / 704 (27.27%)
    221 / 705 (31.35%)
    64 / 192 (33.33%)
         occurrences all number
    380
    394
    121
    Skin and subcutaneous tissue disorders
    ALOPECIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    64 / 704 (9.09%)
    65 / 705 (9.22%)
    18 / 192 (9.38%)
         occurrences all number
    68
    70
    19
    PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    68 / 704 (9.66%)
    104 / 705 (14.75%)
    31 / 192 (16.15%)
         occurrences all number
    81
    138
    50
    RASH
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    38 / 704 (5.40%)
    51 / 705 (7.23%)
    14 / 192 (7.29%)
         occurrences all number
    48
    62
    18
    Renal and urinary disorders
    PROTEINURIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    40 / 704 (5.68%)
    48 / 705 (6.81%)
    23 / 192 (11.98%)
         occurrences all number
    59
    83
    27
    Endocrine disorders
    HYPOTHYROIDISM
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    8 / 704 (1.14%)
    35 / 705 (4.96%)
    24 / 192 (12.50%)
         occurrences all number
    8
    36
    25
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    40 / 704 (5.68%)
    34 / 705 (4.82%)
    15 / 192 (7.81%)
         occurrences all number
    45
    40
    17
    BACK PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    63 / 704 (8.95%)
    54 / 705 (7.66%)
    20 / 192 (10.42%)
         occurrences all number
    78
    68
    27
    MUSCULOSKELETAL PAIN
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    35 / 704 (4.97%)
    40 / 705 (5.67%)
    7 / 192 (3.65%)
         occurrences all number
    39
    49
    8
    MYALGIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    22 / 704 (3.13%)
    18 / 705 (2.55%)
    11 / 192 (5.73%)
         occurrences all number
    28
    18
    12
    PAIN IN EXTREMITY
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    38 / 704 (5.40%)
    46 / 705 (6.52%)
    16 / 192 (8.33%)
         occurrences all number
    45
    55
    19
    Infections and infestations
    NASOPHARYNGITIS
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    50 / 704 (7.10%)
    42 / 705 (5.96%)
    21 / 192 (10.94%)
         occurrences all number
    66
    48
    27
    UPPER RESPIRATORY TRACT INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    36 / 704 (5.11%)
    18 / 705 (2.55%)
    4 / 192 (2.08%)
         occurrences all number
    43
    20
    4
    URINARY TRACT INFECTION
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    43 / 704 (6.11%)
    42 / 705 (5.96%)
    15 / 192 (7.81%)
         occurrences all number
    63
    62
    16
    Metabolism and nutrition disorders
    DECREASED APPETITE
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    160 / 704 (22.73%)
    177 / 705 (25.11%)
    71 / 192 (36.98%)
         occurrences all number
    251
    242
    109
    HYPOKALAEMIA
    alternative dictionary used: MedDRA 17
         subjects affected / exposed
    38 / 704 (5.40%)
    59 / 705 (8.37%)
    16 / 192 (8.33%)
         occurrences all number
    55
    87
    21

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    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
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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