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    Clinical Trial Results:
    A Multicenter, Randomized, Double-Blind, Phase 3 Study of Ramucirumab (IMC-1121B) Drug Product and Best Supportive Care (BSC) Versus Placebo and BSC as Second-Line Treatment in Patients With Hepatocellular Carcinoma Following First-Line Therapy With Sorafenib (REACH)

    Summary
    EudraCT number
    		 2010-019318-26
    Trial protocol
    		 FI   DE   CZ   PT   BE   ES   AT   FR   BG   HU   IT   SE   NO  
    Global end of trial date
    17 Mar 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Apr 2016
    First version publication date
    02 Apr 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    I4T-IE-JVBF
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01140347
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Sponsor Trial Number: 13895, Sponsor Trial Alias: I4T-IE-JVBF, Alternate Trial Number: IMC-1121B
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company, 1 877-CTLilly,
    Scientific contact
    Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, 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
    17 Mar 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Mar 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to compare the overall survival (OS; time from randomization to death) in participants with hepatocellular carcinoma (HCC) who had disease progression during or following sorafenib therapy, or were intolerant to this agent. Participants will receive either ramucirumab (IMC 1121B) plus best supportive care (BSC) or placebo plus BSC.
    Protection of trial subjects
    This study was conducted in accordance with International Conference of 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 was conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Oct 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
    Spain: 21
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    Switzerland: 2
    Country: Number of subjects enrolled
    Taiwan: 58
    Country: Number of subjects enrolled
    Thailand: 6
    Country: Number of subjects enrolled
    United States: 37
    Country: Number of subjects enrolled
    Australia: 11
    Country: Number of subjects enrolled
    Austria: 8
    Country: Number of subjects enrolled
    Belgium: 8
    Country: Number of subjects enrolled
    Brazil: 27
    Country: Number of subjects enrolled
    Bulgaria: 6
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    Czech Republic: 20
    Country: Number of subjects enrolled
    Finland: 3
    Country: Number of subjects enrolled
    France: 59
    Country: Number of subjects enrolled
    Germany: 40
    Country: Number of subjects enrolled
    Hong Kong: 24
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Italy: 51
    Country: Number of subjects enrolled
    Japan: 93
    Country: Number of subjects enrolled
    Korea, Republic of: 70
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Norway: 2
    Country: Number of subjects enrolled
    Philippines: 1
    Country: Number of subjects enrolled
    Portugal: 2
    Country: Number of subjects enrolled
    Romania: 7
    Worldwide total number of subjects
    565
    EEA total number of subjects
    233
    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)
    308
    From 65 to 84 years
    253
    85 years and over
    4

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants who died due to any cause or were alive and on study at conclusion but off treatment were considered to have completed the study.

    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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ramucirumab + BSC
    Arm description
    		 Ramucirumab: 8 milligrams/kilogram (mg/kg) intravenous (IV) infusion every 2 weeks. Best supportive care (BSC): Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ramucirumab
    Investigational medicinal product code
    Other name
    LY3009806, IMC-1121B
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    8 milligrams/kilogram (mg/kg) intravenous (IV) every 2 weeks

    Arm title
    		 Placebo + BSC
    Arm description
    		 Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo + BSC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    8 mg/kg IV every 2 weeks

    Number of subjects in period 1
    		Ramucirumab + BSC Placebo + BSC
    Started
    283
    282
    Received at Least 1 Dose of Study Drug
    277
    276
    Completed
    265
    268
    Not completed
    18
    14
         Consent withdrawn by subject
    13
    8
         Lost to follow-up
    5
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ramucirumab + BSC
    Reporting group description
    		 Ramucirumab: 8 milligrams/kilogram (mg/kg) intravenous (IV) infusion every 2 weeks. Best supportive care (BSC): Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.

    Reporting group title
    Placebo + BSC
    Reporting group description
    		 Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.

    Reporting group values
    		 Ramucirumab + BSC Placebo + BSC Total
    Number of subjects
    		 283 282 282
    Age categorical
    Unable to enter data due to EudraCT system limitation, see below for age categorical data.
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.9 ± 11.56 62.5 ± 11.1 -
    Gender categorical
    Unable to enter ramucirumab data due to EudraCT system limitation, see below for gender categorical data.
    Units: Subjects
        Male
    		 242 242
        Female
    		 40 40
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 23 20 43
        Not Hispanic or Latino
    		 253 260 513
        Unknown or Not Reported
    		 7 2 9
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 131 135 266
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 5 3 8
        White
    		 139 137 276
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 8 7 15
    Region of Enrollment
    Units: Subjects
        United States
    		 17 20 37
        Portugal
    		 0 2 2
        Philippines
    		 1 0 1
        Taiwan
    		 33 25 58
        Hong Kong
    		 14 10 24
        Spain
    		 9 12 21
        Thailand
    		 5 1 6
        Israel
    		 1 1 2
        Switzerland
    		 1 1 2
        Italy
    		 33 18 51
        France
    		 32 27 59
        Australia
    		 3 8 11
        Netherlands
    		 2 1 3
        Korea, Republic of
    		 28 42 70
        Finland
    		 0 3 3
        Austria
    		 4 4 8
        Czech Republic
    		 11 9 20
        Hungary
    		 1 0 1
        Canada
    		 0 1 1
        Belgium
    		 3 5 8
        Brazil
    		 15 12 27
        Romania
    		 3 4 7
        Bulgaria
    		 2 4 6
        Germany
    		 19 21 40
        Norway
    		 1 1 2
        Japan
    		 45 48 93
        Sweden
    		 0 2 2
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 149 159 308
        From 65-84 years
    		 131 122 253
        85 years and over
    		 3 1 4
    Gender categorical
    Units: Subjects
        Male
    		 236 242 478
        Female
    		 47 40 87

    End points

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    End points reporting groups
    Reporting group title
    Ramucirumab + BSC
    Reporting group description
    		 Ramucirumab: 8 milligrams/kilogram (mg/kg) intravenous (IV) infusion every 2 weeks. Best supportive care (BSC): Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.

    Reporting group title
    Placebo + BSC
    Reporting group description
    		 Placebo: 8 mg/kg IV infusion every 2 weeks. BSC: Palliative and supportive care for disease-related symptoms and toxicity associated with treatment as deemed medically necessary and appropriate in the opinion of the investigator.

    Primary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time from the date of randomization to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up were censored on the last date the participant was known to be alive.
    End point type
    Primary
    End point timeframe
    Randomization to death from any cause (up to 37 months)
    End point values
    		 Ramucirumab + BSC Placebo + BSC
    Number of subjects analysed
    283
    282
    Units: months
        median (confidence interval 95%)
    9.17 (8.05 to 10.64)
    7.62 (6.01 to 9.33)
    Statistical analysis title
    		 STATISTICAL ANALYSIS 1
    Comparison groups
    Placebo + BSC v Ramucirumab + BSC
    Number of subjects included in analysis
    565
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    P-value
    		 = 0.1391
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.866
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.717
         upper limit
    		 1.046
    Notes
    [1] - Hazard Ratio (HR) with 95% confidence interval (CI) was estimated using a stratified Cox proportional hazards regression model using the Interactive Web Response System (IWRS) stratification factors (geographical regions and etiology of liver disease).

    Secondary: Progression-Free Survival (PFS)

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    End point title
    		 Progression-Free Survival (PFS)
    End point description
    PFS was defined as time from date of randomization until date of objectively determined progressive disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or death from any cause. PD was defined as ≥20% increase in sum of diameters (SOD) of target lesions, taking as reference smallest sum on study (including baseline sum if it was smallest). Sum must show a ≥5 millimeter (mm) increase. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. In primary analysis, participants alive and without PD were censored at day of last adequate tumor assessment; progression or deaths without progression occurring immediately after ≥2 missed tumor assessments, were censored at day of the last adequate tumor assessment prior to missing assessments; participants who began new anticancer therapy were censored at day of the last adequate tumor assessment prior to start of new anticancer therapy.
    End point type
    Secondary
    End point timeframe
    Randomization to Progressive Disease (PD) (up to 36 months)
    End point values
    		 Ramucirumab + BSC Placebo + BSC
    Number of subjects analysed
    283
    282
    Units: months
        median (confidence interval 95%)
    2.79 (2.69 to 3.94)
    2.1 (1.58 to 2.69)
    Statistical analysis title
    		 STATISTICAL ANALYSIS 1
    Comparison groups
    Placebo + BSC v Ramucirumab + BSC
    Number of subjects included in analysis
    565
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.625
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.522
         upper limit
    		 0.75
    Notes
    [2] - HR with 95% CI was estimated using a stratified Cox proportional hazards regression model using the IWRS stratification factors (geographical regions and etiology of liver disease).

    Secondary: Percentage of Participants with Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

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    End point title
    		 Percentage of Participants with Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
    End point description
    ORR was defined, using RECIST v1.1 criteria, as the percentage of participants who achieved a best overall response of CR or PR. CR was defined as the disappearance of all lesions and any intratumor arterial enhancement in target lesions, the normalization of the tumor marker level and all lymph nodes short axis reduced to <10 mm. PR was defined as ≥30% decrease in the SOD of target lesions, including the short axes of any target lymph nodes, taking as reference the baseline SOD of target lesions, no new lesions and stable nontarget lesions. Percentage of participants was calculated as: (number of participants with CR or PR / number of participants randomized) * 100.
    End point type
    Secondary
    End point timeframe
    Baseline to the date of first evidence of confirmed CR or PR (up to 37 months)
    End point values
    		 Ramucirumab + BSC Placebo + BSC
    Number of subjects analysed
    283
    282
    Units: percentage of participants
        number (confidence interval 95%)
    7.1 (4.6 to 10.7)
    0.7 (0.2 to 2.5)
    Statistical analysis title
    		 STATISTICAL ANALYSIS 1
    Comparison groups
    Placebo + BSC v Ramucirumab + BSC
    Number of subjects included in analysis
    565
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [3] - Cochran-Mantel-Haenszel (CMH) adjusted for geographic region and etiology liver disease.

    Secondary: Time to Radiographic Progression (TTP)

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    End point title
    		 Time to Radiographic Progression (TTP)
    End point description
    TTP was defined as the time from randomization to the first radiographically documented PD. PD was defined, using RECIST v1.1 criteria, as ≥20% increase in SOD of target lesions, taking as reference smallest sum on study (including baseline sum if it was the smallest). Sum must show an absolute increase of ≥5 mm. Appearance of ≥1 new lesions and unequivocal progression of existing non-target lesions were considered progression. Participants without PD were censored at the day of the last adequate tumor assessment. Progression occurred immediately after ≥2 missed tumor assessments and were censored at the day of the last adequate tumor assessment prior to the missing assessments. Participants who began new anticancer therapy were censored at the day of their last adequate tumor assessment prior to start of new anticancer therapy.
    End point type
    Secondary
    End point timeframe
    Randomization to PD (up to 36 months)
    End point values
    		 Ramucirumab + BSC Placebo + BSC
    Number of subjects analysed
    283
    282
    Units: months
        median (confidence interval 95%)
    3.48 (2.76 to 4.47)
    2.63 (1.58 to 2.76)
    Statistical analysis title
    		 STATISTICAL ANALYSIS 1
    Comparison groups
    Placebo + BSC v Ramucirumab + BSC
    Number of subjects included in analysis
    565
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.593
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.487
         upper limit
    		 0.722
    Notes
    [4] - HR with 95% CI was estimated using a stratified Cox proportional hazards regression model using the IWRS stratification factors (geographical regions and etiology of liver disease).

    Secondary: Change from Baseline in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)

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    End point title
    		 Change from Baseline in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
    End point description
    The FHSI-8 is a self-administered 8-item questionnaire that measures a participant's symptoms in the domains of jaundice, stomach pain/discomfort weight loss, and fatigue. Participants rated each item on a 5-point scale from 0 (not at all) to 4 (very much). Item scores were calculated as outlined in the FACIT manual. FHSI-8 total score was the sum of each item's score with a total score ranging from 0 (highly symptomatic) to 32 (asymptomatic).
    End point type
    Secondary
    End point timeframe
    Baseline, Prior to infusion on Day 1 of Cycle 4, Cycle 10, and Cycle 16 (14-day cycles), and end of treatment (up to 34 months)
    End point values
    		 Ramucirumab + BSC Placebo + BSC
    Number of subjects analysed
    169
    199
    Units: units on a scale
    arithmetic mean (standard deviation)
        Cycle 4 (n=166, 147)
    -1.26 ± 3.164
    -0.81 ± 4.623
        Cycle 10 (n=70, 45)
    -1.28 ± 3.989
    -0.01 ± 4.378
        Cycle 16 (n=47, 24)
    -0.97 ± 4.095
    0.75 ± 3.768
        End of Treatment (n=169, 199)
    -2.44 ± 5.561
    -2.86 ± 5.618
    No statistical analyses for this end point

    Secondary: Change from Baseline in European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score

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    End point title
    		 Change from Baseline in European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score
    End point description
    The EQ-5D is a self-reported, 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire related to the participant's current health state. Each question was scored using a 3 level scale (no problems, some problems, or extreme problems). EQ-5D health state was defined by combining responses from each of the 5 dimensions into a weighted health-state index score according to the United Kingdom (UK) population based algorithm where 0 = death and 1 = perfect health.
    End point type
    Secondary
    End point timeframe
    Baseline, Prior to Infusion on Day 1 of Cycle 4, Cycle 10, and Cycle 16 (14-day cycles), end of treatment (up to 34 months)
    End point values
    		 Ramucirumab + BSC Placebo + BSC
    Number of subjects analysed
    166
    190
    Units: units on a scale
    arithmetic mean (standard deviation)
        Cycle 4 (n=166, 145)
    -0.038 ± 0.189
    -0.046 ± 0.245
        Cycle 10 (n=71, 45)
    -0.054 ± 0.212
    0.003 ± 0.148
        Cycle 16 (n=47, 25)
    -0.062 ± 0.214
    -0.012 ± 0.085
        End of Treatment (n=166, 190)
    -0.129 ± 0.29
    -0.144 ± 0.28
    No statistical analyses for this end point

    Secondary: Number of Participants with Adverse Events (AEs) and the Number of Participants Who Died

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    End point title
    		 Number of Participants with Adverse Events (AEs) and the Number of Participants Who Died
    End point description
    The number of participants with serious AEs (SAEs), other non-serious AEs and participants who died. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
    End point type
    Secondary
    End point timeframe
    Baseline to study completion (up to 37 months)
    End point values
    		 Ramucirumab + BSC Placebo + BSC
    Number of subjects analysed
    277
    276
    Units: participants
    number (not applicable)
        SAEs
    123
    92
        Other Non-SAEs
    254
    235
        Died
    215
    220
    No statistical analyses for this end point

    Secondary: Maximum Concentration (Cmax) of Ramucirumab, Cycle 1

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    End point title
    		 Maximum Concentration (Cmax) of Ramucirumab, Cycle 1 [5]
    End point description
    End point type
    Secondary
    End point timeframe
    1 hour following the completion of Cycle 1 (14-day cycle) infusion
    Notes
    [5] - 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: Pharmacokinetic assays are only performed on specimens from participants with exposure to study drug.
    End point values
    		 Ramucirumab + BSC
    Number of subjects analysed
    247
    Units: micrograms/milliliter (µg/mL)
        geometric mean (geometric coefficient of variation)
    149.6 ± 36.9
    No statistical analyses for this end point

    Secondary: Cmax of Ramucirumab, Cycle 4

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    End point title
    		 Cmax of Ramucirumab, Cycle 4 [6]
    End point description
    End point type
    Secondary
    End point timeframe
    1 hour following completion of Cycle 4 (14-day cycles) infusion
    Notes
    [6] - 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: Pharmacokinetic assays are only performed on specimens from participants with exposure to study drug.
    End point values
    		 Ramucirumab + BSC
    Number of subjects analysed
    140
    Units: µg/mL
        geometric mean (geometric coefficient of variation)
    189.5 ± 39.1
    No statistical analyses for this end point

    Secondary: Cmax of Ramucirumab, Cycle 7

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    End point title
    		 Cmax of Ramucirumab, Cycle 7 [7]
    End point description
    End point type
    Secondary
    End point timeframe
    1 hour following completion of Cycle 7 (14-day cycles) infusion
    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: Pharmacokinetic assays are only performed on specimens from participants with exposure to study drug.
    End point values
    		 Ramucirumab + BSC
    Number of subjects analysed
    81
    Units: µg/mL
        geometric mean (geometric coefficient of variation)
    184.4 ± 56.3
    No statistical analyses for this end point

    Secondary: Number of Participants with Treatment-Emergent Positive Anti-Ramucirumab Response [Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)]

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    End point title
    		 Number of Participants with Treatment-Emergent Positive Anti-Ramucirumab Response [Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)]
    End point description
    Participants were considered positive for anti-ramucirumab antibodies [anti-drug antibodies (ADA)] if the post-treatment sample had an increase of at least 4-fold in titer from the pretreatment values. If the pretreatment value was not detected or was not present, a 1:20 post-treatment titer was required to indicate treatment emergence of ADA.
    End point type
    Secondary
    End point timeframe
    Prior to treatment and 1 hour post end of infusion for Cycles 1, 4 and 7 (14-day cycles)
    End point values
    		 Ramucirumab + BSC Placebo + BSC
    Number of subjects analysed
    241
    231
    Units: participants
        number (not applicable)
    10
    7
    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
    Safety population includes any participants who received at least 1 dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Ramucirumab 8 mg/kg I.V. infusion every 2 weeks
    Reporting group description
    		 -

    Reporting group title
    Placebo 8 mg/kg I.V. infusion every 2 weeks
    Reporting group description
    		 -

    Serious adverse events
    		 Ramucirumab 8 mg/kg I.V. infusion every 2 weeks Placebo 8 mg/kg I.V. infusion every 2 weeks
    Total subjects affected by serious adverse events
         subjects affected / exposed
    124 / 277 (44.77%)
    92 / 276 (33.33%)
         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)
    liver carcinoma ruptured
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 276 (0.72%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    malignant neoplasm progression
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    23 / 277 (8.30%)
    16 / 276 (5.80%)
         occurrences causally related to treatment / all
    0 / 30
    0 / 22
         deaths causally related to treatment / all
    0 / 17
    0 / 14
    metastases to bone
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    metastases to central nervous system
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    metastases to lung
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    small intestine adenocarcinoma
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tumour associated fever
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tumour pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    4 / 276 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    deep vein thrombosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypertension
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    shock haemorrhagic
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    chills
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    death
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    extravasation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fatigue
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    2 / 276 (0.72%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    general physical health deterioration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    9 / 277 (3.25%)
    3 / 276 (1.09%)
         occurrences causally related to treatment / all
    2 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    generalised oedema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hernia obstructive
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperthermia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malaise
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    multi-organ failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    non-cardiac chest pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oedema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oedema peripheral
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    7 / 277 (2.53%)
    3 / 276 (1.09%)
         occurrences causally related to treatment / all
    2 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sudden death
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Immune system disorders
    anaphylactic reaction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    acute respiratory distress syndrome
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    dyspnoea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    2 / 276 (0.72%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemoptysis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypoxia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pleural effusion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    3 / 276 (1.09%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         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 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    2 / 276 (0.72%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    pulmonary haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    mental status changes
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    blood bilirubin increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    blood creatinine increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    general physical condition abnormal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    liver function test abnormal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (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
    fall
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    femur fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infusion related reaction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    cardiac failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pericardial effusion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    supraventricular tachycardia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    central nervous system lesion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebral infarction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    coma hepatic
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    convulsion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diplegia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dizziness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    encephalopathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic encephalopathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    12 / 277 (4.33%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    8 / 16
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mental impairment
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peripheral motor neuropathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    somnolence
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spinal cord compression
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    subarachnoid haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tongue biting
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    disseminated intravascular coagulation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutropenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombocytopenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    retinal detachment
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal distension
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    abdominal pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    6 / 277 (2.17%)
    9 / 276 (3.26%)
         occurrences causally related to treatment / all
    1 / 7
    1 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    abdominal pain upper
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ascites
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    8 / 277 (2.89%)
    3 / 276 (1.09%)
         occurrences causally related to treatment / all
    0 / 8
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diarrhoea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    duodenal ulcer
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dysphagia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    food poisoning
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric antral vascular ectasia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric varices haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastroduodenitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    7 / 277 (2.53%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    5 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemorrhoids
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ileus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    inguinal hernia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intestinal obstruction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    irritable bowel syndrome
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    large intestine perforation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    melaena
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nausea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophageal haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    oesophageal varices haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    10 / 276 (3.62%)
         occurrences causally related to treatment / all
    1 / 5
    7 / 12
         deaths causally related to treatment / all
    0 / 1
    1 / 1
    pancreatitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peritoneal haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (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 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    umbilical hernia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    upper gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    varices oesophageal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    acute hepatic failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    bile duct stone
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholangitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 277 (1.81%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholangitis acute
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic cirrhosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    6 / 277 (2.17%)
    5 / 276 (1.81%)
         occurrences causally related to treatment / all
    5 / 9
    0 / 9
         deaths causally related to treatment / all
    2 / 4
    0 / 5
    hepatic function abnormal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatorenal syndrome
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    hyperbilirubinaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    3 / 276 (1.09%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypertransaminasaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    jaundice
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    jaundice cholestatic
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    liver disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    portal vein thrombosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    dermatitis allergic
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    skin lesion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    skin ulcer
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    renal failure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    renal failure acute
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    renal impairment
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    arthritis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    back pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    4 / 276 (1.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    flank pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    musculoskeletal chest pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neck pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pathological fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spinal pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    anal abscess
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bacteraemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    campylobacter infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    candida sepsis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    device related infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    device related sepsis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    influenza
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    liver abscess
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lung infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lobar pneumonia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peritonitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peritonitis bacterial
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    3 / 276 (1.09%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    pneumonia klebsiella
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia bacterial
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary sepsis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (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 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    2 / 276 (0.72%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 3
         deaths causally related to treatment / all
    1 / 2
    0 / 1
    septic shock
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    upper respiratory tract infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Metabolism and nutrition disorders
    cachexia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    decreased appetite
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dehydration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diabetes mellitus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypercalcaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperglycaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperkalaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypertriglyceridaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypocalcaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypoglycaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyponatraemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Ramucirumab 8 mg/kg I.V. infusion every 2 weeks Placebo 8 mg/kg I.V. infusion every 2 weeks
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    265 / 277 (95.67%)
    257 / 276 (93.12%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    cancer pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    3 / 276 (1.09%)
         occurrences all number
    1
    3
    haemangioma
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    haemangioma of skin
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    keratoacanthoma
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    malignant neoplasm progression
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 277 (1.81%)
    3 / 276 (1.09%)
         occurrences all number
    6
    3
    melanocytic naevus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    metastases to lung
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    metastatic pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    pyogenic granuloma
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    skin papilloma
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    squamous cell carcinoma
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    tongue neoplasm malignant stage unspecified
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    2
    tumour pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    4 / 276 (1.45%)
         occurrences all number
    4
    5
    tumour thrombosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    deep vein thrombosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    embolism
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    extravasation blood
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    femoral artery occlusion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    flushing
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    0 / 276 (0.00%)
         occurrences all number
    3
    0
    haematoma
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    7 / 277 (2.53%)
    2 / 276 (0.72%)
         occurrences all number
    7
    2
    haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    hot flush
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    hypertension
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    55 / 277 (19.86%)
    20 / 276 (7.25%)
         occurrences all number
    104
    43
    hypotension
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    4 / 276 (1.45%)
         occurrences all number
    5
    4
    intermittent claudication
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    lymphostasis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    orthostatic hypotension
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    peripheral coldness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    periphlebitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    thrombophlebitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    3
    0
    vein disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    venous insufficiency
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    2 / 276 (0.72%)
         occurrences all number
    1
    3
    venous lake
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    General disorders and administration site conditions
    application site pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    asthenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    50 / 277 (18.05%)
    36 / 276 (13.04%)
         occurrences all number
    80
    63
    axillary pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    catheter site pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    chest discomfort
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    3 / 276 (1.09%)
         occurrences all number
    2
    4
    chest pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    8 / 276 (2.90%)
         occurrences all number
    4
    10
    chills
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    11 / 277 (3.97%)
    6 / 276 (2.17%)
         occurrences all number
    15
    15
    crepitations
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    drug intolerance
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    drug withdrawal syndrome
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    effusion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    face oedema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    8 / 277 (2.89%)
    1 / 276 (0.36%)
         occurrences all number
    9
    1
    fatigue
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    66 / 277 (23.83%)
    60 / 276 (21.74%)
         occurrences all number
    97
    99
    feeling cold
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    gait disturbance
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences all number
    2
    1
    generalised oedema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    4
    0
    general physical health deterioration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 276 (0.72%)
         occurrences all number
    2
    2
    hernia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    hyperthermia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    0 / 276 (0.00%)
         occurrences all number
    9
    0
    influenza like illness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    6 / 277 (2.17%)
    11 / 276 (3.99%)
         occurrences all number
    9
    25
    infusion site swelling
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    infusion site pruritus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    injection site reaction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    injection site pruritus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    local swelling
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    1 / 276 (0.36%)
         occurrences all number
    4
    2
    localised oedema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    3
    0
    malaise
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 277 (1.81%)
    10 / 276 (3.62%)
         occurrences all number
    6
    11
    medical device complication
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    mucosal inflammation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    6 / 277 (2.17%)
    3 / 276 (1.09%)
         occurrences all number
    10
    5
    mucosal dryness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    non-cardiac chest pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    7 / 276 (2.54%)
         occurrences all number
    3
    7
    oedema peripheral
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    100 / 277 (36.10%)
    50 / 276 (18.12%)
         occurrences all number
    151
    58
    oedema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    3 / 276 (1.09%)
         occurrences all number
    3
    6
    pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    5 / 276 (1.81%)
         occurrences all number
    4
    5
    pyrexia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    42 / 277 (15.16%)
    25 / 276 (9.06%)
         occurrences all number
    59
    32
    suprapubic pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    systemic inflammatory response syndrome
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    thirst
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    ulcer
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    xerosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    Immune system disorders
    cytokine release syndrome
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    0 / 276 (0.00%)
         occurrences all number
    4
    0
    hypersensitivity
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    1 / 276 (0.36%)
         occurrences all number
    4
    1
    seasonal allergy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    balanitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed [1]
    1 / 230 (0.43%)
    0 / 236 (0.00%)
         occurrences all number
    1
    0
    benign prostatic hyperplasia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed [2]
    1 / 230 (0.43%)
    1 / 236 (0.42%)
         occurrences all number
    1
    1
    breast pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    1 / 276 (0.36%)
         occurrences all number
    5
    1
    genital rash
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    gynaecomastia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed [3]
    5 / 230 (2.17%)
    0 / 236 (0.00%)
         occurrences all number
    6
    0
    pelvic pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    pruritus genital
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    rectocele
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed [4]
    1 / 47 (2.13%)
    0 / 40 (0.00%)
         occurrences all number
    1
    0
    scrotal swelling
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed [5]
    0 / 230 (0.00%)
    1 / 236 (0.42%)
         occurrences all number
    0
    1
    sexual dysfunction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    asthma
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    atelectasis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences all number
    2
    1
    bronchial obstruction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    cough
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    41 / 277 (14.80%)
    25 / 276 (9.06%)
         occurrences all number
    54
    29
    diaphragmalgia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    dysphonia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    9 / 277 (3.25%)
    1 / 276 (0.36%)
         occurrences all number
    9
    2
    dyspnoea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    26 / 277 (9.39%)
    26 / 276 (9.42%)
         occurrences all number
    33
    33
    dyspnoea exertional
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    3 / 276 (1.09%)
         occurrences all number
    5
    3
    epistaxis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    38 / 277 (13.72%)
    17 / 276 (6.16%)
         occurrences all number
    48
    22
    haemoptysis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    8 / 277 (2.89%)
    2 / 276 (0.72%)
         occurrences all number
    9
    2
    hiccups
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    6 / 277 (2.17%)
    5 / 276 (1.81%)
         occurrences all number
    7
    6
    hypoxia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    increased upper airway secretion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    interstitial lung disease
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    laryngeal inflammation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    lung infiltration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    nasal dryness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    nasal discomfort
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    nasal mucosal disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    oropharyngeal pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    6 / 277 (2.17%)
    2 / 276 (0.72%)
         occurrences all number
    6
    2
    pleural effusion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    8 / 277 (2.89%)
    9 / 276 (3.26%)
         occurrences all number
    11
    11
    pleurisy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    pneumonitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    productive cough
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    7 / 277 (2.53%)
    5 / 276 (1.81%)
         occurrences all number
    7
    5
    pulmonary artery thrombosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    pulmonary congestion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    pulmonary embolism
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    rales
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    1 / 276 (0.36%)
         occurrences all number
    4
    1
    rhinorrhoea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 276 (0.72%)
         occurrences all number
    2
    2
    rhinitis allergic
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    2 / 276 (0.72%)
         occurrences all number
    1
    2
    rhonchi
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    sinus congestion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    tachypnoea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    upper-airway cough syndrome
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    wheezing
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    abnormal dreams
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    agitation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    anxiety
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    7 / 276 (2.54%)
         occurrences all number
    2
    18
    bulimia nervosa
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    confusional state
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    8 / 277 (2.89%)
    3 / 276 (1.09%)
         occurrences all number
    9
    3
    delirium
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    depressed mood
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    depression
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    9 / 277 (3.25%)
    1 / 276 (0.36%)
         occurrences all number
    9
    6
    disorientation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    insomnia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    19 / 277 (6.86%)
    20 / 276 (7.25%)
         occurrences all number
    20
    20
    mood altered
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    nightmare
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    psychotic disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    psychomotor retardation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    Investigations
    activated partial thromboplastin time prolonged
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    2 / 276 (0.72%)
         occurrences all number
    1
    2
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    13 / 277 (4.69%)
    21 / 276 (7.61%)
         occurrences all number
    34
    33
    albumin urine present
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    alpha 1 foetoprotein increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences all number
    2
    1
    ammonia increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    30 / 277 (10.83%)
    39 / 276 (14.13%)
         occurrences all number
    59
    70
    biopsy liver
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    blood albumin decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    8 / 277 (2.89%)
    1 / 276 (0.36%)
         occurrences all number
    37
    1
    blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    18 / 277 (6.50%)
    14 / 276 (5.07%)
         occurrences all number
    40
    25
    blood bilirubin increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    19 / 277 (6.86%)
    24 / 276 (8.70%)
         occurrences all number
    39
    38
    blood chloride decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    blood creatinine increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 277 (1.81%)
    10 / 276 (3.62%)
         occurrences all number
    15
    12
    blood chloride increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    blood lactate dehydrogenase increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences all number
    2
    1
    blood magnesium decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    blood potassium increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    blood pressure abnormal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    blood pressure increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    blood urea increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    2
    blood urine present
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    blood uric acid increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    1 / 276 (0.36%)
         occurrences all number
    7
    1
    body temperature increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    1 / 276 (0.36%)
         occurrences all number
    4
    1
    breath sounds abnormal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    breath sounds
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    c-reactive protein increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    3 / 276 (1.09%)
         occurrences all number
    1
    4
    cd4 lymphocytes increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    cardiac murmur
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences all number
    2
    2
    coagulation time abnormal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    ejection fraction decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    electrocardiogram t wave inversion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    electrocardiogram qt prolonged
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    gamma-glutamyltransferase increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    6 / 276 (2.17%)
         occurrences all number
    14
    8
    general physical condition abnormal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    haematocrit decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    haemoglobin decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences all number
    5
    1
    heart sounds abnormal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    international normalised ratio increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 276 (0.72%)
         occurrences all number
    2
    2
    lipase increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    liver function test abnormal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 276 (0.72%)
         occurrences all number
    2
    2
    mean cell volume decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    monocyte count increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    neutrophil count decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    occult blood
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    platelet count decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    2
    1
    protein total decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    3
    0
    protein urine present
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    0 / 276 (0.00%)
         occurrences all number
    7
    0
    prothrombin time prolonged
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    sputum abnormal
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    urine output decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    urine ketone body present
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    waist circumference increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    weight decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    9 / 277 (3.25%)
    6 / 276 (2.17%)
         occurrences all number
    12
    6
    weight increased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    1 / 276 (0.36%)
         occurrences all number
    6
    1
    white blood cells urine positive
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    white blood cell count decreased
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    Injury, poisoning and procedural complications
    animal bite
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    anal injury
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    chest injury
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    chillblains
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    clavicle fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    contusion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    4 / 276 (1.45%)
         occurrences all number
    4
    4
    craniocerebral injury
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    excoriation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    3 / 276 (1.09%)
         occurrences all number
    1
    3
    facial bones fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    fall
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    7 / 277 (2.53%)
    0 / 276 (0.00%)
         occurrences all number
    8
    0
    foreign body
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    incision site pruritus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    infusion related reaction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    12 / 277 (4.33%)
    1 / 276 (0.36%)
         occurrences all number
    13
    1
    laceration
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    limb injury
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    lumbar vertebral fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    postoperative wound complication
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    procedural pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences all number
    2
    1
    rib fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    sternal fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    sternal injury
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    stress fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    tongue injury
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    tooth fracture
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    wound
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences all number
    2
    1
    wound haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    aortic valve incompetence
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    bradycardia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    bundle branch block right
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    cardiomyopathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    cyanosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    myocardial infarction
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    palpitations
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 276 (0.72%)
         occurrences all number
    2
    2
    sinus arrhythmia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    sinus tachycardia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    supraventricular tachycardia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    tachycardia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    tricuspid valve disease
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    ageusia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    amnesia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    1 / 276 (0.36%)
         occurrences all number
    4
    1
    aphasia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    aphonia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    asterixis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    autonomic nervous system imbalance
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    balance disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    cerebral ischaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    circadian rhythm sleep disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    clumsiness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    consciousness fluctuating
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    convulsion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences all number
    2
    1
    diabetic neuropathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    disturbance in attention
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    0 / 276 (0.00%)
         occurrences all number
    3
    0
    dizziness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    23 / 277 (8.30%)
    16 / 276 (5.80%)
         occurrences all number
    25
    18
    dysaesthesia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    dysgeusia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    7 / 277 (2.53%)
    3 / 276 (1.09%)
         occurrences all number
    9
    3
    encephalopathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    headache
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    53 / 277 (19.13%)
    15 / 276 (5.43%)
         occurrences all number
    69
    18
    hemiparesis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    hepatic encephalopathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    9 / 277 (3.25%)
    3 / 276 (1.09%)
         occurrences all number
    10
    3
    hyperaesthesia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    hypoaesthesia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    4 / 276 (1.45%)
         occurrences all number
    3
    5
    hypotonia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    intercostal neuralgia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    lethargy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    loss of proprioception
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    memory impairment
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    0 / 276 (0.00%)
         occurrences all number
    3
    0
    movement disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    nervous system disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    neuropathy peripheral
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    2 / 276 (0.72%)
         occurrences all number
    1
    2
    paraesthesia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    8 / 277 (2.89%)
    5 / 276 (1.81%)
         occurrences all number
    14
    6
    parkinson's disease
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    2
    peripheral sensory neuropathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 276 (0.72%)
         occurrences all number
    2
    2
    petit mal epilepsy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    polyneuropathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    2 / 276 (0.72%)
         occurrences all number
    2
    2
    radiculitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    restless legs syndrome
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    sciatica
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    somnolence
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    1 / 276 (0.36%)
         occurrences all number
    6
    1
    spinal cord compression
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    status epilepticus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    stupor
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    syncope
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    transient ischaemic attack
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    tremor
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    3 / 276 (1.09%)
         occurrences all number
    1
    3
    vocal cord paralysis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    29 / 277 (10.47%)
    31 / 276 (11.23%)
         occurrences all number
    54
    44
    disseminated intravascular coagulation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    eosinophilia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    hypochromic anaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    8
    0
    leukocytosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    3 / 277 (1.08%)
    5 / 276 (1.81%)
         occurrences all number
    3
    5
    leukopenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    14 / 277 (5.05%)
    7 / 276 (2.54%)
         occurrences all number
    54
    19
    lymphadenopathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    lymphopenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    7 / 277 (2.53%)
    4 / 276 (1.45%)
         occurrences all number
    16
    7
    neutropenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    16 / 277 (5.78%)
    4 / 276 (1.45%)
         occurrences all number
    80
    8
    neutrophilia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    splenomegaly
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    thrombocytosis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    thrombocytopenia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    48 / 277 (17.33%)
    12 / 276 (4.35%)
         occurrences all number
    189
    26
    Ear and labyrinth disorders
    deafness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    deafness neurosensory
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    ear congestion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    ear discomfort
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    ear haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    hearing impaired
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    tinnitus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    3 / 276 (1.09%)
         occurrences all number
    6
    4
    vestibular disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    vertigo
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    5 / 276 (1.81%)
         occurrences all number
    4
    8
    Eye disorders
    asthenopia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    cataract
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    3 / 276 (1.09%)
         occurrences all number
    1
    3
    conjunctival haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    conjunctival hyperaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    conjunctivitis allergic
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    diabetic retinopathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    disorder of orbit
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    dry eye
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    entropion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    eye disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    eye pruritus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 276 (0.72%)
         occurrences all number
    2
    2
    eye irritation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    eye swelling
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    eyelid oedema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    foreign body sensation in eyes
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    hypermetropia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    ocular hyperaemia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    ocular icterus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences all number
    2
    1
    periorbital oedema
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    photophobia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    presbyopia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    retinal vascular disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    retinopathy
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    visual impairment
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    vision blurred
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    3 / 276 (1.09%)
         occurrences all number
    4
    3
    vitreous floaters
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    2 / 276 (0.72%)
         occurrences all number
    2
    2
    Gastrointestinal disorders
    abdominal discomfort
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    7 / 276 (2.54%)
         occurrences all number
    2
    8
    abdominal distension
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    19 / 277 (6.86%)
    28 / 276 (10.14%)
         occurrences all number
    27
    31
    abdominal hernia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    abdominal pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    45 / 277 (16.25%)
    58 / 276 (21.01%)
         occurrences all number
    63
    86
    abdominal pain lower
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    abdominal pain upper
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    26 / 277 (9.39%)
    25 / 276 (9.06%)
         occurrences all number
    34
    32
    abdominal tenderness
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 276 (0.72%)
         occurrences all number
    2
    2
    abdominal rigidity
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    anal fissure
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    anal haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    anal pruritus
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    aphthous stomatitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    ascites
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    72 / 277 (25.99%)
    40 / 276 (14.49%)
         occurrences all number
    110
    47
    breath odour
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    colitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    3
    0
    constipation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    36 / 277 (13.00%)
    34 / 276 (12.32%)
         occurrences all number
    39
    39
    dental caries
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    1 / 276 (0.36%)
         occurrences all number
    2
    1
    diarrhoea
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    50 / 277 (18.05%)
    38 / 276 (13.77%)
         occurrences all number
    74
    52
    dry mouth
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    6 / 277 (2.17%)
    4 / 276 (1.45%)
         occurrences all number
    7
    4
    duodenal ulcer
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    dyspepsia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    6 / 277 (2.17%)
    11 / 276 (3.99%)
         occurrences all number
    7
    14
    dysphagia
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    2 / 276 (0.72%)
         occurrences all number
    4
    3
    enteritis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    2 / 276 (0.72%)
         occurrences all number
    0
    2
    epigastric discomfort
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    3 / 276 (1.09%)
         occurrences all number
    2
    3
    eructation
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    faecal incontinence
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    faeces discoloured
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    0 / 276 (0.00%)
         occurrences all number
    2
    0
    flatulence
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    4 / 277 (1.44%)
    6 / 276 (2.17%)
         occurrences all number
    4
    7
    food poisoning
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    frequent bowel movements
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    gastric mucosal lesion
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    gastritis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 277 (1.81%)
    5 / 276 (1.81%)
         occurrences all number
    6
    5
    gastric ulcer
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    2 / 277 (0.72%)
    2 / 276 (0.72%)
         occurrences all number
    2
    2
    gastroduodenitis
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    0 / 276 (0.00%)
         occurrences all number
    1
    0
    gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    1 / 277 (0.36%)
    1 / 276 (0.36%)
         occurrences all number
    1
    1
    gastrointestinal disorder
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    gastrointestinal pain
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    0 / 277 (0.00%)
    1 / 276 (0.36%)
         occurrences all number
    0
    1
    gastrooesophageal reflux disease
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    5 / 277 (1.81%)
    4 / 276 (1.45%)
         occurrences all number
    6
    4
    gingival bleeding
    alternative dictionary used: MedDRA 16.1
         subjects affected / exposed
    18 / 277 (6.50%)
    4 / 276 (1.45%)
         occurrences all number
    22
    4
    gingival disorder