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    Clinical Trial Results:
    A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance Pemetrexed plus Best Supportive Care versus Best Supportive Care Immediately Following Induction Treatment for Advanced Non-Small Cell Lung Cancer

    Summary
    EudraCT number
    		 2004-002425-52
    Trial protocol
    		 DE   CZ   AT   HU   IT   ES  
    Global end of trial date
    03 Dec 2013

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Jul 2016
    First version publication date
    02 Aug 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    H3E-MC-JMEN
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00102804
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial ID Number: 5122
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon - Fri 9 AM - 5 PM EST , Eli Lilly and Company, 1 877-CTLilly,
    Scientific contact
    Available Mon - Fri 9 AM - 5 PM EST , Eli Lilly and Company, 1 877-285-4559,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 Dec 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Dec 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study is a randomized Phase 3, double-blind study of maintenance pemetrexed plus best supportive care versus placebo plus best supportive care in Non-Small Cell Lung Cancer (NSCLC). Participants must have received 1 of 6 induction regimens for 4 cycles and did not have progressive disease prior to randomization (enrollment) into this trial.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Mar 2005
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Ethical reason
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 32
    Country: Number of subjects enrolled
    Taiwan: 9
    Country: Number of subjects enrolled
    Greece: 27
    Country: Number of subjects enrolled
    Spain: 49
    Country: Number of subjects enrolled
    Turkey: 11
    Country: Number of subjects enrolled
    Austria: 4
    Country: Number of subjects enrolled
    Italy: 34
    Country: Number of subjects enrolled
    Czech Republic: 7
    Country: Number of subjects enrolled
    Poland: 36
    Country: Number of subjects enrolled
    Brazil: 34
    Country: Number of subjects enrolled
    Croatia: 13
    Country: Number of subjects enrolled
    Romania: 77
    Country: Number of subjects enrolled
    Australia: 27
    Country: Number of subjects enrolled
    Bulgaria: 19
    Country: Number of subjects enrolled
    Netherlands: 14
    Country: Number of subjects enrolled
    Germany: 56
    Country: Number of subjects enrolled
    China: 99
    Country: Number of subjects enrolled
    Korea, Republic of: 46
    Country: Number of subjects enrolled
    India: 55
    Country: Number of subjects enrolled
    Hungary: 14
    Worldwide total number of subjects
    663
    EEA total number of subjects
    350
    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)
    443
    From 65 to 84 years
    220
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants who signed the informed consent form (ICF) and completed the randomized process are presented in the participant flow by the treatment arm to which they were randomized. Participants who did not sign the ICF or complete the randomization process were removed from the database and excluded from all analyses.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Pemetrexed and BSC
    Arm description
    		 Pemetrexed: 500 milligrams per square meter (mg/m^2), intravenous (IV) administration, every (q) 21 days, until disease progression. Best Supportive Care (BSC): Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pemetrexed
    Investigational medicinal product code
    Other name
    LY231514, Alimta
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    500 milligrams per square meter (mg/m^2), intravenous (IV) administration, every (q) 21 days, until disease progression

    Arm title
    		 Placebo and Best Supportive Care (BSC)
    Arm description
    		 Placebo: IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV administration, q 21 days

    Number of subjects in period 1
    		Pemetrexed and BSC Placebo and Best Supportive Care (BSC)
    Started
    441
    222
    Received at least 1 dose of study drug
    434
    222
    Completed
    0
    0
    Not completed
    441
    222
         Adverse event, serious fatal
    5
    6
         Consent withdrawn by subject
    46
    7
         Physician decision
    24
    6
         Adverse event, non-fatal
    37
    3
         Progressive Disease (PD)
    307
    196
         Enrollment Criteria Not Met
    6
    -
         Sponsor Decision
    1
    -
         Alive, Receiving Treatment
    7
    2
         Lost to follow-up
    4
    1
         Satisfactory Response
    2
    -
         Protocol deviation
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Pemetrexed and BSC
    Reporting group description
    		 Pemetrexed: 500 milligrams per square meter (mg/m^2), intravenous (IV) administration, every (q) 21 days, until disease progression. Best Supportive Care (BSC): Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.

    Reporting group title
    Placebo and Best Supportive Care (BSC)
    Reporting group description
    		 Placebo: IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.

    Reporting group values
    		 Pemetrexed and BSC Placebo and Best Supportive Care (BSC) Total
    Number of subjects
    		 441 222
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age Continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 60.6 (54.3 to 67.5) 60.4 (53.8 to 67) -
    Gender, Male/Female
    Units: participants
        Female
    		 0
        Male
    		 0
    Race/Ethnicity, Customized
    Units: Subjects
        Aboriginal
    		 0
        African
    		 0
        Caucasian
    		 0
        East Asian
    		 0
        Hispanic
    		 0
        West Asian
    		 0
    Subject analysis sets

    Subject analysis set title
    Pemetrexed and BSC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pemetrexed: 500 milligrams per square meter (mg/m^2), intravenous (IV) administration, every (q) 21 days, until disease progression. Best Supportive Care (BSC): Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.

    Subject analysis set title
    Placebo and BSC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo: IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.

    Subject analysis sets values
    		 Pemetrexed and BSC Placebo and BSC
    Number of subjects
    441
    222
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    Gender, Male/Female
    Units: participants
        Female
    119
    61
        Male
    322
    161
    Race/Ethnicity, Customized
    Units: Subjects
        Aboriginal
    0
    1
        African
    6
    0
        Caucasian
    279
    149
        East Asian
    104
    50
        Hispanic
    13
    6
        West Asian
    39
    16

    End points

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    End points reporting groups
    Reporting group title
    Pemetrexed and BSC
    Reporting group description
    		 Pemetrexed: 500 milligrams per square meter (mg/m^2), intravenous (IV) administration, every (q) 21 days, until disease progression. Best Supportive Care (BSC): Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.

    Reporting group title
    Placebo and Best Supportive Care (BSC)
    Reporting group description
    		 Placebo: IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.

    Subject analysis set title
    Pemetrexed and BSC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Pemetrexed: 500 milligrams per square meter (mg/m^2), intravenous (IV) administration, every (q) 21 days, until disease progression. Best Supportive Care (BSC): Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.

    Subject analysis set title
    Placebo and BSC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo: IV administration, q 21 days, until disease progression. BSC: Treatment without a specific antineoplastic regimen, given with the intent to maximize quality of life, as judged by the treating physician.

    Primary: Progression-Free survival (PFS) time

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    End point title
    		 Progression-Free survival (PFS) time
    End point description
    PFS time was the elapsed time from the date of randomization to the first date of objective progression of disease or death from any cause. PFS was censored at the date of the participant’s last tumor assessment for participants who were not known to have died or to have PD as of the data-inclusion cut-off date for analysis. PD, defined using Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0), was at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
    End point type
    Primary
    End point timeframe
    Randomization to measured PD or death from any cause (up to 41 months)
    End point values
    		 Pemetrexed and BSC Placebo and Best Supportive Care (BSC)
    Number of subjects analysed
    441
    222
    Units: months
        median (confidence interval 95%)
    4.27 (4.07 to 4.73)
    2.6 (1.68 to 2.83)
    Statistical analysis title
    		 Statistical Analysis 1 for Primary Endpoint (PFS)
    Statistical analysis description
    The study applied a statistical gatekeeping and alpha-spending scheme such that the statistical power for assessment of Overall Survival at the time of survival maturity will be maintained.
    Comparison groups
    Pemetrexed and BSC v Placebo and Best Supportive Care (BSC)
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 0.61
    Notes
    [1] - The primary analysis estimated the PFS HR using a Cox proportional hazards model (Cox 1972) with assigned treatment as the only covariate. The same hypothesis used for the primary analysis of PFS was used to compare all time-to-event variables (OS, TtP, and TWS).

    Secondary: Overall survival (OS) time

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    End point title
    		 Overall survival (OS) time
    End point description
    OS time was the elapsed time from the date of randomization to the date of death from any cause. OS was censored at the last date of contact for participants who were not known to have died as of the data-inclusion cut-off date for analysis.
    End point type
    Secondary
    End point timeframe
    Randomization to date of death from any cause (up to 41 months)
    End point values
    		 Pemetrexed and BSC Placebo and Best Supportive Care (BSC)
    Number of subjects analysed
    441
    222
    Units: months
        median (confidence interval 95%)
    13.37 (11.93 to 15.87)
    10.58 (8.74 to 12.02)
    No statistical analyses for this end point

    Secondary: Time to objective progressive disease (TPD)

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    End point title
    		 Time to objective progressive disease (TPD)
    End point description
    TPD was the elapsed time from the date of randomization to the first date of objective PD. TPD was censored at the date of the participant’s last tumor assessment for participants who were not known to have PD as of the data-inclusion cut-off date for analysis or who died without objective PD. PD, defined using RECIST v1.0, was at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
    End point type
    Secondary
    End point timeframe
    Randomization to measured PD (up to 41 months)
    End point values
    		 Pemetrexed and BSC Placebo and Best Supportive Care (BSC)
    Number of subjects analysed
    441
    222
    Units: months
        median (confidence interval 95%)
    4.27 (4.11 to 4.73)
    2.6 (1.68 to 2.83)
    No statistical analyses for this end point

    Secondary: Time to worsening of symptoms (TWS)

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    End point title
    		 Time to worsening of symptoms (TWS)
    End point description
    TWS was the elapsed time from the date of randomization to the first date of worsening [defined as a 15-millimeter (mm) increase from baseline based on a 100-mm scale] of each symptom and summary item in the Lung Cancer Symptom Scale (LCSS). The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant (pt) responses to each item were measured using visual analogue scales (VAS) from 0 (for best outcome) to 100 (for worst outcome). TWS was censored at the date of the last LCSS assessment for pts who were not known to have LCSS worsening. *Median (95% confidence interval) TWS for hemoptysis was not calculated due to the high level of censoring.
    End point type
    Secondary
    End point timeframe
    Randomization to worsening of each LCSS item (up to 39 months)
    End point values
    		 Pemetrexed and BSC Placebo and Best Supportive Care (BSC)
    Number of subjects analysed
    441
    222
    Units: months
    median (confidence interval 95%)
        Loss of appetite
    3.78 (2.86 to 4.44)
    4.4 (2.96 to 15.61)
        Fatigue
    3.06 (2.63 to 5.29)
    3.09 (2.43 to 3.98)
        Cough
    6.05 (4.21 to 7.82)
    4.67 (3.06 to 15.61)
        Dyspnea
    5.36 (4.21 to 10.87)
    4.4 (2.83 to 15.61)
        Hemoptysis
    9999 (999 to 99999)
    9999 (999 to 9999)
        Pain
    6.11 (4.57 to 9.56)
    4.63 (3.32 to 5.98)
        Symptomatic distress
    4.21 (3.58 to 5.55)
    3.78 (2.99 to 18.53)
        Interference with activity level
    6.51 (4.34 to 8.18)
    3.98 (2.83 to 15.61)
        Global quality of life
    5.75 (4.37 to 8.41)
    3.71 (2.99 to 5.49)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Complete Response (CR) or Partial Response (PR) (Objective tumor response rate)

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    End point title
    		 Percentage of Participants with a Complete Response (CR) or Partial Response (PR) (Objective tumor response rate)
    End point description
    Response was defined using RECIST v1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined either A) at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LDs or B) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more nontarget lesions. In either case, no new lesions may have appeared. The percentage of participants with CR or PR=(Number of participants with CR or PR)/(Number of participants assessed)*100.
    End point type
    Secondary
    End point timeframe
    Baseline to measured PD (up to 41 months)
    End point values
    		 Pemetrexed and BSC Placebo and Best Supportive Care (BSC)
    Number of subjects analysed
    441
    222
    Units: percentage of participants
        number (confidence interval 95%)
    6.8 (5 to 10)
    1.8 (0 to 5)
    No statistical analyses for this end point

    Secondary: Number of Participants With Adverse Events (AEs)

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    End point title
    		 Number of Participants With Adverse Events (AEs)
    End point description
    Clinically significant events were defined as serious adverse events (SAEs) and other non-serious AEs regardless of causality.  A summary of serious 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 41 Months)
    End point values
    		 Pemetrexed and BSC Placebo and Best Supportive Care (BSC)
    Number of subjects analysed
    438
    218
    Units: participants
    number (not applicable)
        SAEs
    83
    31
        Other Non-Serious AEs
    386
    178
    No statistical analyses for this end point

    Secondary: Maximum Improvement Over Baseline in individual symptom scores and quality of life using the LCSS

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    End point title
    		 Maximum Improvement Over Baseline in individual symptom scores and quality of life using the LCSS
    End point description
    The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant responses to each item were measured using VAS from 0 (for best outcome) to 100 (for worst outcome). The average symptom burden index (ASBI) was the mean of the 6 symptom-specific items. The LCSS total score was the mean of the 9 items.
    End point type
    Secondary
    End point timeframe
    Baseline through 30 days post discontinuation of study treatment (up to 39 Months)
    End point values
    		 Pemetrexed and BSC Placebo and Best Supportive Care (BSC)
    Number of subjects analysed
    403
    197
    Units: units on a scale
    arithmetic mean (standard deviation)
        Loss of appetite (n=403, 197)
    7.3 ( 25.9 )
    10.6 ( 25.25 )
        Fatigue (n=403, 197)
    10.2 ( 27.1 )
    10.4 ( 23.92 )
        Cough (n=402, 197)
    7.6 ( 20.09 )
    6.7 ( 23.81 )
        Dyspnea (n=400, 196)
    7.6 ( 22.5 )
    5.4 ( 20.44 )
        Pain (n=401, 197)
    5.4 ( 20.96 )
    4.3 ( 21.93 )
        Hemoptysis (n=402, 196)
    1.5 ( 9.41 )
    2.1 ( 9.23 )
        Symptom distress (n=401, 196)
    6.5 ( 21.13 )
    8.2 ( 22.5 )
        Interference with activity level (n=400, 197)
    10.8 ( 27.08 )
    9.3 ( 25.5 )
        Global quality of life (n=401, 195)
    10.7 ( 24.94 )
    10.5 ( 22.98 )
        ASBI (n=392, 195)
    3.7 ( 12.34 )
    3.8 ( 13.24 )
        Total LCSS (n=388, 193)
    4.07 ( 12.76 )
    4.04 ( 13.03 )
    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
    H3E-MC-JMEN
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    11.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    Pemetrexed
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo Pemetrexed
    Total subjects affected by serious adverse events
         subjects affected / exposed
    31 / 218 (14.22%)
    83 / 438 (18.95%)
         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)
    meningioma
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    metastases to central nervous system
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tumour pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    deep vein thrombosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pelvic venous thrombosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    superior vena caval occlusion
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    chest pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    death
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    fatigue
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    general physical health deterioration
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mucosal inflammation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    multi-organ failure
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    performance status decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    4 / 438 (0.91%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    balanitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed [1]
    0 / 158 (0.00%)
    1 / 321 (0.31%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    atelectasis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bronchial obstruction
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cough
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dyspnoea
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    6 / 218 (2.75%)
    14 / 438 (3.20%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    haemoptysis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypoxia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pleural effusion
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia aspiration
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    pneumonitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary fibrosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    respiratory failure
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Psychiatric disorders
    confusional state
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    weight decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    femur fracture
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rib fracture
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    acute myocardial infarction
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    atrial fibrillation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cardiac failure
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cardio-respiratory arrest
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    myocardial ischaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    myocardial infarction
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         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 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sinus tachycardia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    convulsion
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dizziness
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    epilepsy
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    headache
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hemiparesis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypoaesthesia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ischaemic stroke
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    paraparesis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    paraplegia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    partial seizures
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spinal cord compression
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         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 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    6 / 438 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    anaemia of malignant disease
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    febrile neutropenia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    leukopenia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutropenia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    2 / 438 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombocytopenia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    vertigo
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (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 pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    constipation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dysphagia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haematemesis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    large intestine perforation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         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 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    reflux oesophagitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    dysuria
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nephrolithiasis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    renal failure
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    renal failure acute
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary retention
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (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 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bone pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intervertebral disc degeneration
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    joint effusion
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    muscle contracture
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    muscular weakness
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    myalgia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pain in extremity
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    bronchitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    2 / 438 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    bronchopneumonia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    erysipelas
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    herpes zoster
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oral candidiasis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    10 / 438 (2.28%)
         occurrences causally related to treatment / all
    0 / 3
    3 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    pulmonary sepsis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    respiratory tract infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    skin infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    3 / 438 (0.68%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urosepsis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    viral upper respiratory tract infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    anorexia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dehydration
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diabetic ketoacidosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypercalcaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypercholesterolaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (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 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo Pemetrexed
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    178 / 218 (81.65%)
    386 / 438 (88.13%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    angiolipoma
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    cancer pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    4 / 218 (1.83%)
    11 / 438 (2.51%)
         occurrences all number
    4
    11
    metastatic pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    neoplasm
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    oesophageal carcinoma
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    tumour pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    5 / 218 (2.29%)
    5 / 438 (1.14%)
         occurrences all number
    5
    5
    Vascular disorders
    deep vein thrombosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    flushing
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    5 / 218 (2.29%)
    8 / 438 (1.83%)
         occurrences all number
    7
    10
    haemorrhage
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hot flush
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    2 / 438 (0.46%)
         occurrences all number
    1
    2
    hypertension
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    4 / 218 (1.83%)
    11 / 438 (2.51%)
         occurrences all number
    4
    11
    hypotension
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    6 / 438 (1.37%)
         occurrences all number
    3
    6
    orthostatic hypotension
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    peripheral ischaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    phlebitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    shock
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    superior vena caval occlusion
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    3 / 438 (0.68%)
         occurrences all number
    1
    3
    thrombosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    3 / 438 (0.68%)
         occurrences all number
    2
    3
    Surgical and medical procedures
    medical device implantation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    pneumatic compression therapy
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    tumour excision
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    10 / 218 (4.59%)
    48 / 438 (10.96%)
         occurrences all number
    11
    74
    axillary pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    catheter site erythema
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    chest discomfort
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    14
    chest pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    16 / 218 (7.34%)
    44 / 438 (10.05%)
         occurrences all number
    17
    67
    chills
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    7 / 438 (1.60%)
         occurrences all number
    0
    9
    condition aggravated
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    cyst
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    extravasation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    face oedema
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    6 / 438 (1.37%)
         occurrences all number
    2
    7
    facial pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    fatigue
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    49 / 218 (22.48%)
    145 / 438 (33.11%)
         occurrences all number
    63
    227
    feeling abnormal
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    gait disturbance
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    general physical health deterioration
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    7 / 438 (1.60%)
         occurrences all number
    0
    9
    influenza like illness
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    10 / 438 (2.28%)
         occurrences all number
    4
    17
    injection site reaction
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences all number
    0
    4
    irritability
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    localised oedema
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences all number
    0
    4
    malaise
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    4
    mucosal inflammation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    12 / 438 (2.74%)
         occurrences all number
    2
    19
    obstruction
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    oedema
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    12 / 438 (2.74%)
         occurrences all number
    1
    16
    oedema peripheral
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    27 / 438 (6.16%)
         occurrences all number
    3
    34
    pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    13 / 218 (5.96%)
    24 / 438 (5.48%)
         occurrences all number
    13
    28
    peripheral coldness
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    pyrexia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    25 / 218 (11.47%)
    56 / 438 (12.79%)
         occurrences all number
    33
    78
    swelling
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    visceral oedema
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    Immune system disorders
    contrast media allergy
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hypersensitivity
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    6 / 438 (1.37%)
         occurrences all number
    1
    8
    seasonal allergy
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    balanitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed [2]
    0 / 158 (0.00%)
    1 / 321 (0.31%)
         occurrences all number
    0
    1
    breast swelling
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    pelvic pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    testicular disorder
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed [3]
    0 / 158 (0.00%)
    1 / 321 (0.31%)
         occurrences all number
    0
    1
    testicular pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed [4]
    0 / 158 (0.00%)
    1 / 321 (0.31%)
         occurrences all number
    0
    1
    vaginal haemorrhage
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed [5]
    0 / 60 (0.00%)
    2 / 117 (1.71%)
         occurrences all number
    0
    2
    Respiratory, thoracic and mediastinal disorders
    atelectasis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    bronchial obstruction
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    cough
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    47 / 218 (21.56%)
    95 / 438 (21.69%)
         occurrences all number
    50
    118
    dysphonia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    4 / 218 (1.83%)
    2 / 438 (0.46%)
         occurrences all number
    4
    2
    dyspnoea
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    43 / 218 (19.72%)
    98 / 438 (22.37%)
         occurrences all number
    45
    118
    dyspnoea exertional
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    2 / 438 (0.46%)
         occurrences all number
    1
    2
    epistaxis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    5 / 438 (1.14%)
         occurrences all number
    1
    8
    haemoptysis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    10 / 218 (4.59%)
    24 / 438 (5.48%)
         occurrences all number
    11
    26
    hiccups
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    9 / 438 (2.05%)
         occurrences all number
    3
    17
    hypoxia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    3
    pharyngolaryngeal pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    5 / 218 (2.29%)
    10 / 438 (2.28%)
         occurrences all number
    5
    11
    pleural effusion
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    pleurisy
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    pleuritic pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    pneumonitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    postnasal drip
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    5
    productive cough
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    11 / 438 (2.51%)
         occurrences all number
    3
    15
    pulmonary embolism
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    pulmonary haemorrhage
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    0 / 438 (0.00%)
         occurrences all number
    3
    0
    rales
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    rhinitis allergic
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    4 / 438 (0.91%)
         occurrences all number
    1
    7
    rhinorrhoea
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    6 / 438 (1.37%)
         occurrences all number
    0
    6
    rhonchi
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    wheezing
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    4 / 438 (0.91%)
         occurrences all number
    1
    4
    Psychiatric disorders
    abnormal behaviour
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    agitation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    anxiety
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    5 / 438 (1.14%)
         occurrences all number
    1
    5
    confusional state
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences all number
    0
    4
    depressed mood
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    3
    depression
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    9 / 438 (2.05%)
         occurrences all number
    1
    9
    insomnia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    8 / 218 (3.67%)
    28 / 438 (6.39%)
         occurrences all number
    8
    31
    suicidal ideation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    tic
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    Investigations
    alanine aminotransferase
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    alanine aminotransferase decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    9 / 218 (4.13%)
    60 / 438 (13.70%)
         occurrences all number
    11
    87
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    8 / 218 (3.67%)
    52 / 438 (11.87%)
         occurrences all number
    10
    63
    blood albumin decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    blood alkaline phosphatase
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    2
    1
    blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    4 / 218 (1.83%)
    12 / 438 (2.74%)
         occurrences all number
    4
    16
    blood bilirubin increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    blood bicarbonate decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    blood calcium decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    blood creatinine decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    3 / 438 (0.68%)
         occurrences all number
    1
    10
    blood creatinine increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    4 / 218 (1.83%)
    21 / 438 (4.79%)
         occurrences all number
    4
    30
    blood fibrinogen increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    blood glucose increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    3
    blood iron decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    blood lactate dehydrogenase increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    9 / 438 (2.05%)
         occurrences all number
    1
    15
    blood potassium decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    blood potassium increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    2
    blood sodium decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    blood sodium increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    blood uric acid increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    c-reactive protein increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    creatinine renal clearance decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    18 / 438 (4.11%)
         occurrences all number
    2
    28
    forced expiratory volume decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    gamma-glutamyltransferase increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    5 / 218 (2.29%)
    6 / 438 (1.37%)
         occurrences all number
    5
    7
    glomerular filtration rate
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    3
    glomerular filtration rate decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    5 / 438 (1.14%)
         occurrences all number
    0
    10
    granulocyte count decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    granulocyte count increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    2
    0
    haemoglobin
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    haemoglobin decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    19 / 438 (4.34%)
         occurrences all number
    2
    30
    neutrophil count decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    11 / 438 (2.51%)
         occurrences all number
    1
    16
    neutrophil count increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    4
    platelet count
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    platelet count decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    5 / 438 (1.14%)
         occurrences all number
    2
    5
    platelet count increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    1 / 438 (0.23%)
         occurrences all number
    3
    1
    red blood cell count decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    2 / 438 (0.46%)
         occurrences all number
    1
    5
    red blood cell microcytes present
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    renal function test abnormal
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    3
    sensory level
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    total bile acids increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    transaminases increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    troponin t
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    weight decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    17 / 438 (3.88%)
         occurrences all number
    3
    20
    weight increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    5 / 438 (1.14%)
         occurrences all number
    1
    5
    white blood cell count decreased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences all number
    0
    5
    white blood cell count increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    1 / 438 (0.23%)
         occurrences all number
    3
    1
    Injury, poisoning and procedural complications
    arterial injury
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    contusion
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    3 / 438 (0.68%)
         occurrences all number
    1
    3
    fall
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    foot fracture
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    fracture
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    incision site pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    procedural headache
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    radiation skin injury
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    rib fracture
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    thermal burn
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    wound
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    Cardiac disorders
    arrhythmia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    arrhythmia supraventricular
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    atrial fibrillation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    atrial tachycardia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    bradycardia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    cyanosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    myocardial ischaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    palpitations
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    1 / 438 (0.23%)
         occurrences all number
    3
    2
    pericardial effusion
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    sinus tachycardia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    tachycardia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    3 / 438 (0.68%)
         occurrences all number
    1
    4
    Nervous system disorders
    ageusia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    aphonia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    aphasia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    ataxia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    5 / 438 (1.14%)
         occurrences all number
    0
    6
    balance disorder
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    brain injury
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    burning sensation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    cerebral ischaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    0 / 438 (0.00%)
         occurrences all number
    2
    0
    cognitive disorder
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    2 / 438 (0.46%)
         occurrences all number
    1
    2
    coma
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    convulsion
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    3 / 438 (0.68%)
         occurrences all number
    1
    3
    depressed level of consciousness
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    disturbance in attention
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    dizziness
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    7 / 218 (3.21%)
    34 / 438 (7.76%)
         occurrences all number
    7
    39
    dysgeusia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    10 / 438 (2.28%)
         occurrences all number
    1
    14
    dysaesthesia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    2
    dysphasia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    formication
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    headache
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    19 / 218 (8.72%)
    51 / 438 (11.64%)
         occurrences all number
    26
    62
    hemicephalalgia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hemiparesis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hypoaesthesia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    5 / 438 (1.14%)
         occurrences all number
    3
    6
    memory impairment
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    neuralgia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    4 / 438 (0.91%)
         occurrences all number
    1
    4
    neuropathy peripheral
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    10 / 438 (2.28%)
         occurrences all number
    2
    11
    neurotoxicity
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    paraesthesia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    11 / 218 (5.05%)
    27 / 438 (6.16%)
         occurrences all number
    12
    29
    peripheral motor neuropathy
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    peripheral sensory neuropathy
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    6 / 218 (2.75%)
    22 / 438 (5.02%)
         occurrences all number
    6
    22
    poor quality sleep
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    somnolence
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    speech disorder
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    stupor
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    syncope
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    syncope vasovagal
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    transient ischaemic attack
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    tremor
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    3
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    12 / 218 (5.50%)
    65 / 438 (14.84%)
         occurrences all number
    15
    97
    anaemia of malignant disease
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    febrile neutropenia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    leukocytosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    leukopenia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    5 / 218 (2.29%)
    25 / 438 (5.71%)
         occurrences all number
    8
    64
    lymph node pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    lymphadenopathy
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    4
    lymphopenia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    3 / 438 (0.68%)
         occurrences all number
    1
    3
    neutropenia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    5 / 218 (2.29%)
    21 / 438 (4.79%)
         occurrences all number
    5
    66
    neutrophilia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    thrombocythaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    thrombocytopenia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    17 / 438 (3.88%)
         occurrences all number
    3
    29
    Ear and labyrinth disorders
    cerumen impaction
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    deafness
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    3
    ear discomfort
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    ear pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hypoacusis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    motion sickness
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    tinnitus
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    5 / 438 (1.14%)
         occurrences all number
    1
    5
    vertigo
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    2 / 438 (0.46%)
         occurrences all number
    1
    2
    Eye disorders
    blepharitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    cataract
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    2 / 438 (0.46%)
         occurrences all number
    1
    2
    conjunctivitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    20 / 438 (4.57%)
         occurrences all number
    1
    24
    conjunctivitis allergic
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    dry eye
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    eye pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    eye swelling
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    eyelid oedema
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    3
    keratoconjunctivitis sicca
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences all number
    0
    4
    lacrimation increased
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    20 / 438 (4.57%)
         occurrences all number
    0
    21
    ocular surface disease
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    3 / 438 (0.68%)
         occurrences all number
    2
    5
    photophobia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    pterygium
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    vision blurred
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    8 / 438 (1.83%)
         occurrences all number
    1
    10
    visual acuity reduced
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    visual disturbance
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    abdominal distension
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    4 / 438 (0.91%)
         occurrences all number
    2
    4
    abdominal pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    8 / 218 (3.67%)
    18 / 438 (4.11%)
         occurrences all number
    8
    18
    abdominal pain lower
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    abdominal pain upper
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    7 / 438 (1.60%)
         occurrences all number
    11
    7
    aphthous stomatitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    ascites
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    constipation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    17 / 218 (7.80%)
    59 / 438 (13.47%)
         occurrences all number
    22
    85
    dental caries
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    diarrhoea
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    15 / 218 (6.88%)
    52 / 438 (11.87%)
         occurrences all number
    17
    88
    dry mouth
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    10 / 438 (2.28%)
         occurrences all number
    3
    10
    dysphagia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    4 / 438 (0.91%)
         occurrences all number
    2
    5
    dyspepsia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    6 / 218 (2.75%)
    13 / 438 (2.97%)
         occurrences all number
    21
    18
    faecal incontinence
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    faecaloma
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    0 / 438 (0.00%)
         occurrences all number
    2
    0
    flatulence
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences all number
    0
    7
    gastric disorder
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    gastritis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    4 / 438 (0.91%)
         occurrences all number
    1
    5
    gastrointestinal pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    gastrooesophageal reflux disease
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    1 / 438 (0.23%)
         occurrences all number
    2
    1
    gingival pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    gingivitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    haemorrhoids
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hiatus hernia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    ileus
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    inflammatory bowel disease
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    lip ulceration
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    mouth ulceration
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    3
    nausea
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    22 / 218 (10.09%)
    102 / 438 (23.29%)
         occurrences all number
    24
    209
    odynophagia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    4 / 438 (0.91%)
         occurrences all number
    1
    5
    oesophageal haemorrhage
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    oesophagitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    oral pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    2 / 438 (0.46%)
         occurrences all number
    1
    2
    paraesthesia oral
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    4
    periodontal disease
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    rectal haemorrhage
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    stomatitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    19 / 438 (4.34%)
         occurrences all number
    1
    22
    tongue black hairy
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    tongue coated
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    toothache
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences all number
    0
    4
    vomiting
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    9 / 218 (4.13%)
    56 / 438 (12.79%)
         occurrences all number
    12
    88
    Hepatobiliary disorders
    cholelithiasis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hepatic pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    hepatitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hepatomegaly
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hyperbilirubinaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    acne
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    1 / 438 (0.23%)
         occurrences all number
    2
    2
    alopecia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    21 / 438 (4.79%)
         occurrences all number
    1
    23
    dermal cyst
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    dermatitis acneiform
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    4 / 218 (1.83%)
    2 / 438 (0.46%)
         occurrences all number
    4
    6
    dermatosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    2
    dermatitis exfoliative
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    dry skin
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    5 / 438 (1.14%)
         occurrences all number
    1
    6
    erythema
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    hyperhidrosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    12 / 438 (2.74%)
         occurrences all number
    0
    15
    madarosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    nail disorder
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    night sweats
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    2 / 438 (0.46%)
         occurrences all number
    1
    2
    pain of skin
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    0 / 438 (0.00%)
         occurrences all number
    2
    0
    periorbital oedema
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    petechiae
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    5
    photosensitivity reaction
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    pigmentation disorder
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences all number
    0
    7
    pruritus
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    7 / 218 (3.21%)
    18 / 438 (4.11%)
         occurrences all number
    8
    22
    pruritus generalised
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    psoriasis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    rash
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    14 / 218 (6.42%)
    62 / 438 (14.16%)
         occurrences all number
    16
    81
    rash pruritic
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    3
    skin discolouration
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    skin exfoliation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    skin hyperpigmentation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    9 / 438 (2.05%)
         occurrences all number
    1
    9
    skin hypopigmentation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    skin toxicity
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    swelling face
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    urticaria
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    4
    Renal and urinary disorders
    bladder spasm
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    calculus bladder
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    dysuria
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    8
    glycosuria
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    haematuria
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    haemorrhage urinary tract
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    incontinence
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    micturition urgency
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    nocturia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    pollakiuria
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    4
    renal failure
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    3
    urinary hesitation
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    3
    urinary incontinence
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    1 / 438 (0.23%)
         occurrences all number
    2
    1
    urinary retention
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    5 / 438 (1.14%)
         occurrences all number
    0
    5
    Endocrine disorders
    goitre
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hyperthyroidism
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hypothyroidism
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    7 / 218 (3.21%)
    12 / 438 (2.74%)
         occurrences all number
    7
    16
    arthritis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    back pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    8 / 218 (3.67%)
    41 / 438 (9.36%)
         occurrences all number
    8
    48
    bone pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    10 / 218 (4.59%)
    14 / 438 (3.20%)
         occurrences all number
    10
    14
    flank pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    2
    muscle spasms
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    3
    musculoskeletal chest pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    5 / 218 (2.29%)
    8 / 438 (1.83%)
         occurrences all number
    5
    8
    muscular weakness
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    5 / 438 (1.14%)
         occurrences all number
    2
    6
    musculoskeletal discomfort
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    musculoskeletal pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    5 / 218 (2.29%)
    12 / 438 (2.74%)
         occurrences all number
    6
    14
    myalgia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    5 / 218 (2.29%)
    15 / 438 (3.42%)
         occurrences all number
    7
    17
    neck pain
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    5 / 218 (2.29%)
    3 / 438 (0.68%)
         occurrences all number
    6
    5
    pain in extremity
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    9 / 218 (4.13%)
    11 / 438 (2.51%)
         occurrences all number
    11
    14
    pain in jaw
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    7
    scleroderma
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    tendonitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    Infections and infestations
    abscess
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    bronchitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    15 / 438 (3.42%)
         occurrences all number
    2
    17
    candidiasis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    cellulitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    2
    cystitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    3
    diverticulitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    ear infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    erysipelas
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    folliculitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    fungal infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    gastroenteritis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    gastroenteritis viral
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hepatic infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    herpes simplex
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    herpes virus infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    herpes zoster
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    3 / 438 (0.68%)
         occurrences all number
    1
    3
    infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    3 / 438 (0.68%)
         occurrences all number
    3
    3
    influenza
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    10 / 438 (2.28%)
         occurrences all number
    0
    12
    laryngitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    0 / 438 (0.00%)
         occurrences all number
    2
    0
    lower respiratory tract infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    lung infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    3 / 438 (0.68%)
         occurrences all number
    1
    3
    nasopharyngitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    14 / 438 (3.20%)
         occurrences all number
    3
    17
    oral candidiasis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    4 / 438 (0.91%)
         occurrences all number
    0
    4
    oral herpes
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    0 / 438 (0.00%)
         occurrences all number
    2
    0
    otitis media
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    paronychia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    parotitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    pharyngitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    pneumonia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    2 / 438 (0.46%)
         occurrences all number
    2
    2
    pyothorax
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    respiratory tract infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    respiratory tract infection viral
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    rhinitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    sinusitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    3
    soft tissue infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    tonsillitis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    tooth abscess
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    tooth infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    upper respiratory tract infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    15 / 438 (3.42%)
         occurrences all number
    3
    20
    urinary tract infection
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    4 / 218 (1.83%)
    5 / 438 (1.14%)
         occurrences all number
    4
    7
    Metabolism and nutrition disorders
    acidosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    alcohol intolerance
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    alkalosis
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    anorexia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    40 / 218 (18.35%)
    124 / 438 (28.31%)
         occurrences all number
    43
    238
    dehydration
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    7 / 438 (1.60%)
         occurrences all number
    1
    8
    diabetes mellitus
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    3 / 438 (0.68%)
         occurrences all number
    0
    3
    fluid retention
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    3
    glucose tolerance impaired
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hypercalcaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    2 / 218 (0.92%)
    3 / 438 (0.68%)
         occurrences all number
    3
    3
    hypercholesterolaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    1 / 438 (0.23%)
         occurrences all number
    1
    2
    hypercreatininaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hyperglycaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    6 / 218 (2.75%)
    18 / 438 (4.11%)
         occurrences all number
    7
    20
    hyperkalaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    4 / 438 (0.91%)
         occurrences all number
    1
    6
    hyperlipidaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    hypernatraemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    3
    hypertriglyceridaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    1
    0
    hyperuricaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    3 / 218 (1.38%)
    1 / 438 (0.23%)
         occurrences all number
    3
    1
    hypoalbuminaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    2 / 438 (0.46%)
         occurrences all number
    1
    3
    hypocalcaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    2 / 438 (0.46%)
         occurrences all number
    0
    2
    hypokalaemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    4 / 438 (0.91%)
         occurrences all number
    2
    4
    hyponatraemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    7 / 438 (1.60%)
         occurrences all number
    0
    7
    hypophosphataemia
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    1 / 218 (0.46%)
    0 / 438 (0.00%)
         occurrences all number
    2
    0
    increased appetite
    alternative dictionary used: MedDRA 11.0
         subjects affected / exposed
    0 / 218 (0.00%)
    1 / 438 (0.23%)
         occurrences all number
    0
    1
    Notes
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Feb 2007
    Protocol H3E-MC-JMEN was amended to change the primary objective from Overall Survival (OS) to Progression Free Survival.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Four participants (pts) assigned to placebo received pemetrexed; pts analyzed for efficacy as randomized. Three treated pts did not sign ICF, 1 treated pt signed ICF but did not complete entire randomization process; pts excluded from all analyses.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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