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    Clinical Trial Results:
    A Randomized, Double-blind, Multicenter Phase 3 Study of Irinotecan, Folinic Acid, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab or Placebo in Patients With Metastatic Colorectal Carcinoma Progressive During or Following First-Line Combination Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine

    Summary
    EudraCT number
    		 2010-021037-32
    Trial protocol
    		 FI   FR   AT   NL   ES   PT   DE   IT   SE   BE   DK   GR   HU   SI  
    Global end of trial date
    20 Jun 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Jun 2017
    First version publication date
    25 Jun 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    I4T-MC-JVBB
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01183780
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 13856
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    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
    20 Jun 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Jun 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to compare overall survival in participants with metastatic colorectal cancer treated with either ramucirumab and FOLFIRI or placebo and FOLFIRI.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Dec 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 283
    Country: Number of subjects enrolled
    Portugal: 4
    Country: Number of subjects enrolled
    Taiwan: 11
    Country: Number of subjects enrolled
    Greece: 16
    Country: Number of subjects enrolled
    Spain: 111
    Country: Number of subjects enrolled
    Israel: 14
    Country: Number of subjects enrolled
    Italy: 37
    Country: Number of subjects enrolled
    India: 3
    Country: Number of subjects enrolled
    France: 27
    Country: Number of subjects enrolled
    Puerto Rico: 3
    Country: Number of subjects enrolled
    Australia: 35
    Country: Number of subjects enrolled
    Denmark: 11
    Country: Number of subjects enrolled
    Netherlands: 14
    Country: Number of subjects enrolled
    Korea, Republic of: 47
    Country: Number of subjects enrolled
    Finland: 12
    Country: Number of subjects enrolled
    Austria: 18
    Country: Number of subjects enrolled
    Czech Republic: 77
    Country: Number of subjects enrolled
    Hungary: 47
    Country: Number of subjects enrolled
    Argentina: 18
    Country: Number of subjects enrolled
    Belgium: 52
    Country: Number of subjects enrolled
    Brazil: 5
    Country: Number of subjects enrolled
    Romania: 33
    Country: Number of subjects enrolled
    Germany: 44
    Country: Number of subjects enrolled
    Japan: 136
    Country: Number of subjects enrolled
    Sweden: 14
    Worldwide total number of subjects
    1072
    EEA total number of subjects
    517
    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)
    645
    From 65 to 84 years
    425
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Completers included participants who died from any cause and participants who were alive and on study at conclusion however were off treatment.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ramucirumab + FOLFIRI
    Arm description
    		 On Day 1 of each 14-day cycle, participants received ramucirumab followed by other study treatment in the following sequence: Irinotecan, Folinic Acid and 5-Fluorouracil (FOLFIRI). Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. Ramucirumab: 8 milligrams/kilogram (mg/kg) administered intravenously. Irinotecan: 180 mg/m^2 administered intravenously. Folinic Acid: 400 mg/m^2 administered intravenously. 5-Fluorouracil: 400 mg/m^2 bolus immediately followed by 2400 mg/m^2 continuous infusion.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ramucirumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    8 milligrams/kilogram (mg/kg) administered intravenously.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    180 mg/m² administered intravenously.

    Investigational medicinal product name
    Folinic Acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg/m² administered intravenously.

    Investigational medicinal product name
    5-Fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    400 mg/m² bolus immediately followed by 2400 mg/m² continuous infusion.

    Arm title
    		 Placebo + FOLFIRI
    Arm description
    		 On Day 1 of each 14-day cycle, participants received placebo followed by other study treatment in the following sequence: Irinotecan, Folinic Acid and 5-Fluorouracil. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. Placebo: Administered intravenously. Irinotecan: 180 mg/m^2 administered intravenously. Folinic Acid: 400 mg/m^2 administered intravenously. 5-Fluorouracil: 400 mg/m^2 bolus immediately followed by 2400 mg/m^2 continuous infusion.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered intravenously.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    180 mg/m² administered intravenously.

    Investigational medicinal product name
    Folinic Acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg/m² administered intravenously.

    Investigational medicinal product name
    5-Fluorouracil
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    8 milligrams/kilogram (mg/kg) administered intravenously.

    Number of subjects in period 1
    		Ramucirumab + FOLFIRI Placebo + FOLFIRI
    Started
    536
    536
    received at least 1 dose of study drug
    528
    529
    Completed
    505
    511
    Not completed
    31
    25
         Consent withdrawn by subject
    25
    14
         Lost to follow-up
    6
    11

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    		 Baseline Analysis Population: All randomized participants.

    Reporting group values
    		 Overall Study Total
    Number of subjects
    		 1072 1072
    Age Categorical
    Units:
    Age Continuous
    Units: years
        median (full range (min-max))
    		 62 (21 to 87) -
    Gender, Male/Female
    Units: Subjects
        Male
    		 615 615
        Female
    		 457 457
    Region of Enrollment
    Units: Subjects
        United States
    		 283 283
        Portugal
    		 4 4
        Taiwan
    		 11 11
        Greece
    		 16 16
        Spain
    		 111 111
        Israel
    		 14 14
        Italy
    		 37 37
        India
    		 3 3
        France
    		 27 27
        Puerto Rico
    		 3 3
        Australia
    		 35 35
        Denmark
    		 11 11
        Netherlands
    		 14 14
        Korea, Republic of
    		 47 47
        Finland
    		 12 12
        Austria
    		 18 18
        Czech Republic
    		 77 77
        Hungary
    		 47 47
        Argentina
    		 18 18
        Belgium
    		 52 52
        Brazil
    		 5 5
        Romania
    		 33 33
        Germany
    		 44 44
        Japan
    		 136 136
        Sweden
    		 14 14
    Age, Categorical
    Units: Subjects
        <=18 years
    		 0 0
        Between 18 and 65 years
    		 645 645
        >=65 years
    		 427 427
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 77 77
        Not Hispanic or Latino
    		 469 469
        Unknown or Not Reported
    		 526 526
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 1 1
        Asian
    		 214 214
        Native Hawaiian or Other Pacific Islander
    		 2 2
        Black or African American
    		 30 30
        White
    		 815 815
        More than one race
    		 3 3
        Unknown or Not Reported
    		 7 7

    End points

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    End points reporting groups
    Reporting group title
    Ramucirumab + FOLFIRI
    Reporting group description
    		 On Day 1 of each 14-day cycle, participants received ramucirumab followed by other study treatment in the following sequence: Irinotecan, Folinic Acid and 5-Fluorouracil (FOLFIRI). Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. Ramucirumab: 8 milligrams/kilogram (mg/kg) administered intravenously. Irinotecan: 180 mg/m^2 administered intravenously. Folinic Acid: 400 mg/m^2 administered intravenously. 5-Fluorouracil: 400 mg/m^2 bolus immediately followed by 2400 mg/m^2 continuous infusion.

    Reporting group title
    Placebo + FOLFIRI
    Reporting group description
    		 On Day 1 of each 14-day cycle, participants received placebo followed by other study treatment in the following sequence: Irinotecan, Folinic Acid and 5-Fluorouracil. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met. Placebo: Administered intravenously. Irinotecan: 180 mg/m^2 administered intravenously. Folinic Acid: 400 mg/m^2 administered intravenously. 5-Fluorouracil: 400 mg/m^2 bolus immediately followed by 2400 mg/m^2 continuous infusion.

    Primary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time in months from the date of randomization to the date of death from any cause. For participants not known to have died as of the cut-off date, OS was censored at the last known date alive. Analysis Population Description : All randomized participants. Participants censored: Ramucirumab + FOLFIRI group = 164; Placebo + FOLFIRI= 139.
    End point type
    Primary
    End point timeframe
    Randomization to Date of Death from Any Cause Up to 39.36 Months
    End point values
    		 Ramucirumab + FOLFIRI Placebo + FOLFIRI
    Number of subjects analysed
    536
    536
    Units: months
        median (confidence interval 95%)
    13.3 (12.4 to 14.5)
    11.7 (10.8 to 12.7)
    Statistical analysis title
    		 OS
    Comparison groups
    Ramucirumab + FOLFIRI v Placebo + FOLFIRI
    Number of subjects included in analysis
    1072
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.0219 [2]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.844
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 0.976
    Notes
    [1] - The analysis was performed on stratified data.
    [2] - The analysis was performed on stratified data.

    Secondary: Progression-free survival (PFS) time

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    End point title
    		 Progression-free survival (PFS) time
    End point description
    PFS was defined as the time from the date of randomization until the date of objectively determined progressive disease (PD) [according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v). 1.1] or death due to any cause, whichever was first. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Participants who died without a reported prior progression were considered to have progressed on the day of their death. Participants who did not progress or were lost to follow-up were censored at the day of their last radiographic tumor assessment. Analysis Population Description : All randomized participants. Participants censored: Ramucirumab + FOLFIRI = 60; Placebo + FOLFIRI = 42.
    End point type
    Secondary
    End point timeframe
    Randomization to Measured PD or Date of Death from Any Cause Up to 38.01 Months
    End point values
    		 Ramucirumab + FOLFIRI Placebo + FOLFIRI
    Number of subjects analysed
    536
    536
    Units: months
        median (confidence interval 95%)
    5.7 (5.5 to 6.2)
    4.5 (4.2 to 5.4)
    Statistical analysis title
    		 PFS
    Statistical analysis description
    Analysis was performed on stratified data.
    Comparison groups
    Ramucirumab + FOLFIRI v Placebo + FOLFIRI
    Number of subjects included in analysis
    1072
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.0005 [4]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.793
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.697
         upper limit
    		 0.903
    Notes
    [3] - Analysis was performed on stratified data.
    [4] - Analysis was performed on stratified data.

    Secondary: Percentage of participants achieving an objective response (objective response rate)

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    End point title
    		 Percentage of participants achieving an objective response (objective response rate)
    End point description
    The objective response rate is equal to the proportion of participants achieving a best overall response of partial response or complete response (PR + CR). Response was defined using RECIST, v. 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and normalization of tumor marker level of non-target lesions; PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameter. Analysis Population Description : All randomized participants.
    End point type
    Secondary
    End point timeframe
    Randomization until Disease Progression Up to 38.01 Months
    End point values
    		 Ramucirumab + FOLFIRI Placebo + FOLFIRI
    Number of subjects analysed
    536
    536
    Units: percentage of participants
        number (confidence interval 95%)
    13.4 (10.7 to 16.6)
    12.5 (9.8 to 15.6)
    Statistical analysis title
    		 Objective Response Rate
    Comparison groups
    Ramucirumab + FOLFIRI v Placebo + FOLFIRI
    Number of subjects included in analysis
    1072
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6336
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Change From Baseline in EuroQol- 5D (EQ-5D)

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    End point title
    		 Change From Baseline in EuroQol- 5D (EQ-5D)
    End point description
    The EQ-5D is a generic, multidimensional, health status instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). A negative change indicated a worsening of the participant's health status. Analysis Population Description : All randomized participants who had EQ-5D assessed at baseline and 30-day FU.
    End point type
    Secondary
    End point timeframe
    Baseline and 30-Day Follow-Up (FU) up to 171 Weeks
    End point values
    		 Ramucirumab + FOLFIRI Placebo + FOLFIRI
    Number of subjects analysed
    308
    310
    Units: units on a scale
        arithmetic mean (standard deviation)
    -0.097 ± 0.279
    -0.103 ± 0.264
    No statistical analyses for this end point

    Secondary: Change From Baseline in European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 Global Health Status

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    End point title
    		 Change From Baseline in European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 Global Health Status
    End point description
    The EORTC QLQ-C30 (v. 3.0) is a self-administered, cancer-specific questionnaire with multidimensional scales assessing 15 domains (5 functional domains, 9 symptoms, and global health status). A linear transformation was applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For the functional domains and global health status scale, higher scores represent a better level of functioning. For symptom scales, higher scores represent a greater degree of symptoms. Maximum improvement is the best post-baseline change. Analysis Population Description : All randomized participants who had EORTC QLQ-C30 assessed at baseline and post-baseline.
    End point type
    Secondary
    End point timeframe
    Baseline Up to 171 Weeks
    End point values
    		 Ramucirumab + FOLFIRI Placebo + FOLFIRI
    Number of subjects analysed
    491
    486
    Units: units on a scale
        arithmetic mean (standard deviation)
    4 ± 20.61
    6.6 ± 18.84
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies

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    End point title
    		 Percentage of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies
    End point description
    Blood samples were tested to determine if a participant reacted to ramucirumab by producing anti-ramucirumab antibodies. Samples were identified as treatment emergent anti-drug antibody (TE ADA) if the post-treatment sample had an increase of at least 4 fold in titer from pre-treatment values. If the pre-treatment value was not detected or was not present, a 1:20 post-treatment titer was required to indicate treatment emergence. The percentage of participants with TE ADA was calculated as: (the number of participants with TE ADA / total number of participants with at least 1 post-treatment immunogenicity sample analyzed)*100. Analysis Population Description : All participants who received study treatment and who had immunogenicity samples analyzed at the specified time points.
    End point type
    Secondary
    End point timeframe
    Cycles 1, 3, 5, and 30-Day FU
    End point values
    		 Ramucirumab + FOLFIRI Placebo + FOLFIRI
    Number of subjects analysed
    516 [5]
    512 [6]
    Units: percentage of participants
    number (not applicable)
        Immunogenicity Any Time During Study
    5.6
    5.5
        Immunogenicity Post-Treatment
    3.1
    3.8
    Notes
    [5] - n=516 for Immunogenicity Any Time During Study. n=47 for Immunogenicity Post-Treatment.
    [6] - n=512 Immunogenicity Any Time During Study. n=473 Immunogenicity Post-Treatment.
    No statistical analyses for this end point

    Secondary: Observed maximum concentration (Cmax) and observed minimum concentration (Cmin) of ramucirumab

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    End point title
    		 Observed maximum concentration (Cmax) and observed minimum concentration (Cmin) of ramucirumab [7]
    End point description
    All randomized participants who received at least one dose of study drug and had evaluable data for Cmin and Cmax.
    End point type
    Secondary
    End point timeframe
    Preinfusion and 1 hour postinfusion in Cycles 3, 5, 9, 13, and 17
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetics data were only collected for participants in arm Ramucirumab + FOLFIRI.
    End point values
    		 Ramucirumab + FOLFIRI
    Number of subjects analysed
    248
    Units: micrograms/milliliter (ug/mL)
    geometric mean (geometric coefficient of variation)
        Cmin Dose 3
    46.3 ± 45
        Cmin Dose 5
    65.1 ± 43
        Cmin Dose 9
    77.9 ± 51
        Cmin Dose 13
    75.9 ± 43
        Cmin Dose 17
    72 ± 49
        Cmax Dose 3
    221 ± 37
        Cmax Dose 5
    243 ± 39
        Cmax Dose 9
    262 ± 36
        Cmax Dose 13
    307 ± 33
        Cmax Dose 17
    253 ± 19
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Entire Study
    Adverse event reporting additional description
    I4T-MC-JVBB
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    FOLFIRI + Ramucirumab every 2 weeks
    Reporting group description
    		 -

    Reporting group title
    FOLFIRI + Placebo every 2 weeks
    Reporting group description
    		 -

    Serious adverse events
    		 FOLFIRI + Ramucirumab every 2 weeks FOLFIRI + Placebo every 2 weeks
    Total subjects affected by serious adverse events
         subjects affected / exposed
    198 / 529 (37.43%)
    175 / 528 (33.14%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    colorectal cancer metastatic
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    malignant ascites
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malignant pleural effusion
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    metastases to meninges
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    metastatic neoplasm
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tumour haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tumour pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    aortic dissection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    deep vein thrombosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    embolism
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypertension
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 529 (0.76%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypertensive crisis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypotension
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypovolaemic shock
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    jugular vein thrombosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lymphoedema
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    subclavian vein thrombosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombophlebitis superficial
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vena cava embolism
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    venous thrombosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    cancer surgery
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colostomy closure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    enterostomy
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    high frequency ablation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 529 (0.76%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    chest pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    disease progression
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fatigue
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    5 / 529 (0.95%)
    4 / 528 (0.76%)
         occurrences causally related to treatment / all
    3 / 5
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    general physical health deterioration
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    5 / 528 (0.95%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    hernia obstructive
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malaise
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mucosal inflammation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 529 (0.76%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    5 / 5
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    multi-organ failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    non-cardiac chest pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oedema peripheral
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 529 (0.76%)
    8 / 528 (1.52%)
         occurrences causally related to treatment / all
    0 / 5
    5 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    systemic inflammatory response syndrome
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    ulcer haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    anaphylactic reaction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    drug hypersensitivity
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    pelvic pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dyspnoea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    5 / 528 (0.95%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemoptysis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    interstitial lung disease
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    laryngeal inflammation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lung infiltration
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    pleural effusion
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumothorax
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumothorax spontaneous
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    10 / 529 (1.89%)
    6 / 528 (1.14%)
         occurrences causally related to treatment / all
    7 / 10
    4 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary oedema
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    respiratory arrest
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    respiratory distress
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    alcohol abuse
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    anxiety
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    confusional state
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    delirium
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    depression
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    disorientation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mental status changes
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    suicide attempt
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    blood bilirubin increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    blood creatinine increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    blood culture positive
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    eastern cooperative oncology group performance status worsened
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    international normalised ratio increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutrophil count decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    platelet count decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    weight decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    alcohol poisoning
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ankle fracture
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    compression fracture
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fall
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    5 / 529 (0.95%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    femur fracture
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fibula fracture
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic haematoma
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hip fracture
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lower limb fracture
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lumbar vertebral fracture
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    post procedural urine leak
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    procedural intestinal perforation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spinal fracture
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    stoma site haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    subdural haematoma
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    wound dehiscence
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    pyloric stenosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    acute myocardial infarction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    angina pectoris
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    atrial fibrillation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    atrial flutter
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cardiac failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    cardio-respiratory arrest
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    congestive cardiomyopathy
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    myocardial infarction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    pericarditis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    right ventricular failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Nervous system disorders
    aphasia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebral haematoma
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebral ischaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    cerebrovascular accident
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    dizziness
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dysarthria
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    epilepsy
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    headache
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperammonaemic encephalopathy
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ischaemic stroke
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    memory impairment
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    optic neuritis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    posterior reversible encephalopathy syndrome
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    presyncope
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    syncope
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    febrile neutropenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    15 / 529 (2.84%)
    8 / 528 (1.52%)
         occurrences causally related to treatment / all
    14 / 16
    7 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    leukopenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutropenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    6 / 529 (1.13%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    7 / 7
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombocytopenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombotic microangiopathy
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Eye disorders
    cataract
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    10 / 529 (1.89%)
    14 / 528 (2.65%)
         occurrences causally related to treatment / all
    0 / 12
    1 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    abdominal pain lower
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    abdominal pain upper
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    anal fistula
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    anal haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    anal ulcer
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ascites
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    1 / 2
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    constipation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diarrhoea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    19 / 529 (3.59%)
    18 / 528 (3.41%)
         occurrences causally related to treatment / all
    16 / 20
    18 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dyspepsia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    enteritis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    enterocolitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    gastritis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal inflammation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal perforation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haematemesis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    haemorrhoidal haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hernial eventration
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ileus
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    6 / 528 (1.14%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    incarcerated inguinal hernia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    inflammatory bowel disease
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    inguinal hernia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intestinal haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intestinal obstruction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    8 / 529 (1.51%)
    11 / 528 (2.08%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 11
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    intestinal perforation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    2 / 2
    0 / 0
    large intestinal haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    large intestinal obstruction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    large intestinal stenosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    large intestine perforation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 529 (0.76%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    lower gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    4 / 528 (0.76%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mechanical ileus
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nausea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    8 / 529 (1.51%)
    6 / 528 (1.14%)
         occurrences causally related to treatment / all
    4 / 8
    6 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophageal varices haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophagitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    proctalgia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rectal haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rectal obstruction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rectal perforation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rectal ulcer
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    small intestinal haemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    small intestinal obstruction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    7 / 529 (1.32%)
    5 / 528 (0.95%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    small intestinal perforation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    stomatitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    subileus
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    13 / 529 (2.46%)
    6 / 528 (1.14%)
         occurrences causally related to treatment / all
    9 / 14
    6 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    acute hepatic failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    bile duct obstruction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bile duct stenosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholangitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholangitis chronic
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholecystitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholelithiasis obstructive
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholestasis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic cirrhosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    hepatic failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic function abnormal
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatorenal syndrome
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatotoxicity
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperbilirubinaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    jaundice
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    jaundice cholestatic
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    liver disorder
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    portal hypertension
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    dermal cyst
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    skin ulcer
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    acute prerenal failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haematuria
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hydronephrosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nephrolithiasis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nephrotic syndrome
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    6 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    prerenal failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    renal failure
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    renal failure acute
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    6 / 528 (1.14%)
         occurrences causally related to treatment / all
    1 / 4
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary incontinence
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary retention
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary tract obstruction
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    back pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    musculoskeletal pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neuropathic arthropathy
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rheumatoid arthritis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    abdominal infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    atypical pneumonia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bacteraemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    biliary tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    bronchitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bronchopulmonary aspergillosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    campylobacter gastroenteritis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    clostridium difficile colitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 529 (0.76%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    4 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cystitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    device related infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    device related sepsis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    erysipelas
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    escherichia sepsis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    herpes zoster
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infective exacerbation of chronic obstructive airways disease
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    influenza
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    klebsiella infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    klebsiella sepsis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    localised infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lung abscess
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lung infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mastoiditis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutropenic infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oral candidiasis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pelvic abscess
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pelvic infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    perirectal abscess
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    2 / 528 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peritonitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peritonitis bacterial
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    7 / 529 (1.32%)
    7 / 528 (1.33%)
         occurrences causally related to treatment / all
    3 / 7
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    pyelonephritis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    respiratory tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    salmonellosis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    5 / 529 (0.95%)
    11 / 528 (2.08%)
         occurrences causally related to treatment / all
    0 / 5
    4 / 13
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    septic shock
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    2 / 529 (0.38%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    sinusitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    upper respiratory tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    4 / 529 (0.76%)
    5 / 528 (0.95%)
         occurrences causally related to treatment / all
    1 / 4
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    wound infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    cachexia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    decreased appetite
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    7 / 529 (1.32%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    5 / 8
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dehydration
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    3 / 529 (0.57%)
    6 / 528 (1.14%)
         occurrences causally related to treatment / all
    2 / 4
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperglycaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypoalbuminaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypokalaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    3 / 528 (0.57%)
         occurrences causally related to treatment / all
    1 / 3
    3 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malnutrition
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    1 / 529 (0.19%)
    0 / 528 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tumour lysis syndrome
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    0 / 529 (0.00%)
    1 / 528 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 FOLFIRI + Ramucirumab every 2 weeks FOLFIRI + Placebo every 2 weeks
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    518 / 529 (97.92%)
    510 / 528 (96.59%)
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    147 / 529 (27.79%)
    51 / 528 (9.66%)
         occurrences all number
    287
    108
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    74 / 529 (13.99%)
    62 / 528 (11.74%)
         occurrences all number
    228
    168
    fatigue
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    254 / 529 (48.02%)
    225 / 528 (42.61%)
         occurrences all number
    645
    588
    malaise
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    41 / 529 (7.75%)
    38 / 528 (7.20%)
         occurrences all number
    97
    104
    mucosal inflammation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    91 / 529 (17.20%)
    52 / 528 (9.85%)
         occurrences all number
    218
    92
    oedema peripheral
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    118 / 529 (22.31%)
    50 / 528 (9.47%)
         occurrences all number
    148
    59
    pyrexia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    85 / 529 (16.07%)
    61 / 528 (11.55%)
         occurrences all number
    135
    93
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    69 / 529 (13.04%)
    46 / 528 (8.71%)
         occurrences all number
    88
    60
    dysphonia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    31 / 529 (5.86%)
    5 / 528 (0.95%)
         occurrences all number
    32
    6
    dyspnoea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    56 / 529 (10.59%)
    51 / 528 (9.66%)
         occurrences all number
    86
    70
    epistaxis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    182 / 529 (34.40%)
    80 / 528 (15.15%)
         occurrences all number
    254
    99
    hiccups
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    30 / 529 (5.67%)
    17 / 528 (3.22%)
         occurrences all number
    81
    22
    Psychiatric disorders
    insomnia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    47 / 529 (8.88%)
    54 / 528 (10.23%)
         occurrences all number
    51
    84
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    28 / 529 (5.29%)
    19 / 528 (3.60%)
         occurrences all number
    59
    59
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    34 / 529 (6.43%)
    18 / 528 (3.41%)
         occurrences all number
    57
    42
    blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    36 / 529 (6.81%)
    27 / 528 (5.11%)
         occurrences all number
    66
    57
    neutrophil count decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    137 / 529 (25.90%)
    115 / 528 (21.78%)
         occurrences all number
    437
    278
    platelet count decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    80 / 529 (15.12%)
    36 / 528 (6.82%)
         occurrences all number
    232
    59
    weight decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    76 / 529 (14.37%)
    46 / 528 (8.71%)
         occurrences all number
    124
    69
    white blood cell count decreased
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    49 / 529 (9.26%)
    51 / 528 (9.66%)
         occurrences all number
    146
    136
    Nervous system disorders
    dizziness
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    38 / 529 (7.18%)
    33 / 528 (6.25%)
         occurrences all number
    46
    51
    dysgeusia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    43 / 529 (8.13%)
    39 / 528 (7.39%)
         occurrences all number
    57
    57
    headache
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    80 / 529 (15.12%)
    41 / 528 (7.77%)
         occurrences all number
    114
    69
    peripheral sensory neuropathy
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    33 / 529 (6.24%)
    38 / 528 (7.20%)
         occurrences all number
    57
    49
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    93 / 529 (17.58%)
    117 / 528 (22.16%)
         occurrences all number
    225
    270
    neutropenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    183 / 529 (34.59%)
    131 / 528 (24.81%)
         occurrences all number
    510
    259
    thrombocytopenia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    80 / 529 (15.12%)
    42 / 528 (7.95%)
         occurrences all number
    177
    82
    Gastrointestinal disorders
    abdominal distension
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    22 / 529 (4.16%)
    27 / 528 (5.11%)
         occurrences all number
    26
    29
    abdominal pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    124 / 529 (23.44%)
    123 / 528 (23.30%)
         occurrences all number
    178
    181
    constipation
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    157 / 529 (29.68%)
    132 / 528 (25.00%)
         occurrences all number
    227
    196
    diarrhoea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    315 / 529 (59.55%)
    271 / 528 (51.33%)
         occurrences all number
    881
    798
    dyspepsia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    26 / 529 (4.91%)
    27 / 528 (5.11%)
         occurrences all number
    28
    32
    haemorrhoids
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    27 / 529 (5.10%)
    6 / 528 (1.14%)
         occurrences all number
    33
    7
    nausea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    265 / 529 (50.09%)
    274 / 528 (51.89%)
         occurrences all number
    650
    715
    proctalgia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    27 / 529 (5.10%)
    13 / 528 (2.46%)
         occurrences all number
    35
    16
    stomatitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    166 / 529 (31.38%)
    113 / 528 (21.40%)
         occurrences all number
    380
    235
    vomiting
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    151 / 529 (28.54%)
    143 / 528 (27.08%)
         occurrences all number
    299
    309
    Skin and subcutaneous tissue disorders
    alopecia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    156 / 529 (29.49%)
    168 / 528 (31.82%)
         occurrences all number
    198
    191
    dry skin
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    29 / 529 (5.48%)
    23 / 528 (4.36%)
         occurrences all number
    35
    25
    palmar-plantar erythrodysaesthesia syndrome
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    69 / 529 (13.04%)
    29 / 528 (5.49%)
         occurrences all number
    108
    39
    rash
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    42 / 529 (7.94%)
    36 / 528 (6.82%)
         occurrences all number
    47
    45
    Renal and urinary disorders
    proteinuria
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    94 / 529 (17.77%)
    30 / 528 (5.68%)
         occurrences all number
    227
    40
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    33 / 529 (6.24%)
    22 / 528 (4.17%)
         occurrences all number
    38
    26
    back pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    43 / 529 (8.13%)
    48 / 528 (9.09%)
         occurrences all number
    54
    128
    pain in extremity
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    36 / 529 (6.81%)
    19 / 528 (3.60%)
         occurrences all number
    58
    25
    Infections and infestations
    upper respiratory tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    36 / 529 (6.81%)
    22 / 528 (4.17%)
         occurrences all number
    44
    25
    urinary tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    34 / 529 (6.43%)
    21 / 528 (3.98%)
         occurrences all number
    43
    35
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    203 / 529 (38.37%)
    149 / 528 (28.22%)
         occurrences all number
    382
    359
    dehydration
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    32 / 529 (6.05%)
    26 / 528 (4.92%)
         occurrences all number
    46
    32
    hypoalbuminaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    35 / 529 (6.62%)
    13 / 528 (2.46%)
         occurrences all number
    59
    20
    hypokalaemia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    39 / 529 (7.37%)
    38 / 528 (7.20%)
         occurrences all number
    65
    72

    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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    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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