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    Clinical Trial Results:
    Randomized, Double-blind, Placebo-controlled Study to Evaluate the Long-term Safety and Efficacy of Darbepoetin Alfa Administered at 500 µg Once-Every-3-Weeks in Anemic Subjects With Advanced Stage Non-small Cell Lung Cancer Receiving Multi-cycle Chemotherapy

    Summary
    EudraCT number
    		 2007-005792-34
    Trial protocol
    		 GB   IE   CZ   AT   BE   ES   DE   NL   GR   IT   SI   BG  
    Global end of trial date
    07 Jun 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Jun 2018
    First version publication date
    23 Jun 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20070782
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00858364
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Jun 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Jun 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to demonstrate non-inferiority of overall survival (OS) when comparing subjects on darbepoetin alfa treated to a hemoglobin ceiling of 12.0 g/dL to subjects treated with placebo.
    Protection of trial subjects
    This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines. A copy of the protocol, proposed informed consent form, other written subject information, and any proposed advertising material was submitted to the IEC/IRB for written approval. A copy of the written approval of the protocol and informed consent form was to be received by Amgen before recruitment of subjects into the study and shipment of investigational product. The investigator or his/her designee informed the subject of all aspects pertaining to the subject’s participation in the study before any screening procedures were performed.
    Background therapy
    		 Participants were receiving cyclic chemotherapy for the treatment of NSCLC.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Jul 2009
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 94 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 15
    Country: Number of subjects enrolled
    Germany: 36
    Country: Number of subjects enrolled
    Greece: 53
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    Luxembourg: 2
    Country: Number of subjects enrolled
    Netherlands: 9
    Country: Number of subjects enrolled
    South Africa: 12
    Country: Number of subjects enrolled
    Spain: 20
    Country: Number of subjects enrolled
    Switzerland: 1
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    Bulgaria: 34
    Country: Number of subjects enrolled
    Czech Republic: 90
    Country: Number of subjects enrolled
    Poland: 61
    Country: Number of subjects enrolled
    Romania: 51
    Country: Number of subjects enrolled
    Russian Federation: 118
    Country: Number of subjects enrolled
    Serbia: 41
    Country: Number of subjects enrolled
    Slovenia: 3
    Country: Number of subjects enrolled
    Ukraine: 279
    Country: Number of subjects enrolled
    Argentina: 27
    Country: Number of subjects enrolled
    Brazil: 173
    Country: Number of subjects enrolled
    Chile: 64
    Country: Number of subjects enrolled
    Hong Kong: 8
    Country: Number of subjects enrolled
    Korea, Republic of: 24
    Country: Number of subjects enrolled
    Malaysia: 9
    Country: Number of subjects enrolled
    Mexico: 39
    Country: Number of subjects enrolled
    Philippines: 143
    Country: Number of subjects enrolled
    Taiwan: 24
    Country: Number of subjects enrolled
    India: 509
    Country: Number of subjects enrolled
    Canada: 6
    Country: Number of subjects enrolled
    United States: 292
    Country: Number of subjects enrolled
    China: 372
    Country: Number of subjects enrolled
    Japan: 16
    Worldwide total number of subjects
    2549
    EEA total number of subjects
    390
    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)
    1496
    From 65 to 84 years
    1039
    85 years and over
    14

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 371 centers in Europe, Latin America, Asia, India, North America, Israel, and South Africa.

    Pre-assignment
    Screening details
    		 Eligible subjects were randomized to darbepoetin alfa or placebo in a 2:1 ratio. Randomization was stratified by histology (squamous vs other), screening hemoglobin (< 10.0 g/dL vs ≥ 10.0 g/dL), and geographic region.

    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, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered subcutaneously once every 3 weeks

    Arm title
    		 Darbepoetin alfa
    Arm description
    		 Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Darbepoetin alfa
    Investigational medicinal product code
    Other name
    Aranesp®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered subcutaneously once every 3 weeks

    Number of subjects in period 1
    		Placebo Darbepoetin alfa
    Started
    846
    1703
    Received Study Drug
    837
    1681
    Completed
    642
    1246
    Not completed
    204
    457
         Consent withdrawn by subject
    44
    118
         Administrative decision
    3
    2
         Protocol Deviation
    -
    2
         Other
    9
    17
         Adverse event
    5
    2
         Participants still on-study
    114
    247
         Ineligibility determined
    1
    10
         Lost to follow-up
    24
    54
         Missing
    1
    1
         Noncompliance
    3
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.

    Reporting group title
    Darbepoetin alfa
    Reporting group description
    		 Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.

    Reporting group values
    		 Placebo Darbepoetin alfa Total
    Number of subjects
    		 846 1703 2549
    Age Categorical
    Units: Subjects
        18 - 64 years
    		 482 1014 1496
        65 - 74 years
    		 287 547 834
        75 - 84 years
    		 71 134 205
        ≥ 85 years
    		 6 8 14
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 62.2 ± 9.9 61.6 ± 9.8 -
    Gender Categorical
    Units: Subjects
        Female
    		 281 585 866
        Male
    		 565 1118 1683
    Race
    Units: Subjects
        White or Caucasian
    		 404 808 1212
        Black or African American
    		 27 46 73
        Asian
    		 357 741 1098
        Japanese
    		 7 12 19
        Native Hawaiian or Other Pacific Islander
    		 1 0 1
        Aborigine
    		 0 1 1
        Other
    		 5 14 19
        Hispanic
    		 45 81 126
    Geographic Region
    Stratification factor at the time of randomization. Data are reported for the primary analysis set (all randomized and consented subjects with NSCLC who received at least 1 dose of investigational product).
    Units: Subjects
        Western Europe, Israel and South Africa
    		 54 108 162
        Central and Eastern Europe
    		 220 451 671
        Latin America and Asia
    		 166 337 503
        India
    		 168 339 507
        North America
    		 99 192 291
        China
    		 123 243 366
        Japan
    		 6 10 16
        Participants not in primary analysis set
    		 10 23 33
    Histology
    Stratification factor at the time of randomization. Data are reported for the primary analysis set.
    Units: Subjects
        Squamous
    		 289 589 878
        Non-squamous
    		 547 1091 1638
        Participants not in primary analysis set
    		 10 23 33
    Screening Hemoglobin
    Stratification factor at the time of randomization. Data are reported for the primary analysis set.
    Units: Subjects
        < 10 g/dL
    		 433 870 1303
        ≥ 10 g/dL
    		 403 810 1213
        Participants not in primary analysis set
    		 10 23 33

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.

    Reporting group title
    Darbepoetin alfa
    Reporting group description
    		 Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.

    Primary: Overall survival (OS)

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    End point title
    		 Overall survival (OS)
    End point description
    Overall survival (OS) was defined as the time from randomization to the date of death due to any cause. Participants were censored on the date of last contact (ie, the date the participant was last known to be alive) if they were not known to have died. The analysis was conducted in the primary analysis set which consisted of all randomized and consented participants with non-small cell lung cancer who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    From randomization until death or end of study; a maximum follow-up time was 93.6 months.
    End point values
    		 Placebo Darbepoetin alfa
    Number of subjects analysed
    836
    1680
    Units: months
        median (confidence interval 95%)
    9.260 (8.250 to 10.020)
    9.460 (8.900 to 10.120)
    Statistical analysis title
    		 Primary Analysis of overall Survival
    Statistical analysis description
    The primary analysis used the Cox Proportional Hazard Model stratified by the randomization stratification factors (geographic region, histology, and screening hemoglobin), with treatment group as the only covariate. A hazard ratio < 1.0 indicates a lower risk of death for Darbepoetin Alfa relative to Placebo.
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2516
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.01
    Notes
    [1] - Non-inferiority was declared if the upper confidence limit for the hazard ratio (darbepoetin alfa to placebo) was less than 1.15 using a 1-sided significance level of 0.025.
    Statistical analysis title
    		 Sensitivity Analysis - Unstratified Model
    Statistical analysis description
    As a sensitivity analysis, an unstratified Cox Proportional Hazard Model with treatment group as the only covariate was conducted. A hazard ratio < 1.0 indicates a lower risk of death for darbepoetin alfa relative to placebo.
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2516
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1
    Notes
    [2] - Non-inferiority was declared if the upper confidence limit for the hazard ratio (darbepoetin alfa to placebo) was less than 1.15 using a 1-sided significance level of 0.025.
    Statistical analysis title
    		 Superiority Analysis (Stratified)
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2516
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.07 [4]
    Method
    		 Stratified log-rank test
    Confidence interval
    Notes
    [3] - If non-inferiority was demonstrated for both OS and PFS and superiority was demonstrated for the transfusion endpoint, superiority was then tested for both OS and PFS using the Hochberg procedure to adjust for multiplicity.
    [4] - Stratified by the randomization stratification factors (geographic region, histology, screening hemoglobin).
    Statistical analysis title
    		 Superiority Analysis (Unstratified)
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2516
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.047 [5]
    Method
    		 Logrank
    Confidence interval
    Notes
    [5] - Unstratified log rank test
    Statistical analysis title
    		 OS Adjusted for Cross-in
    Statistical analysis description
    To evaluate the potential effect of cross-in (participants in the placebo group who began treatment with an erythropoiesis-stimulating agent (ESA) at any point after randomization), a sensitivity analysis was conducted that included ESA use as a time-dependent covariate in a Cox regression model stratified by the randomization stratification factors (geographic region, histology, and screening hemoglobin).
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2516
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.02

    Secondary: Progression-free Survival (PFS)

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    End point title
    		 Progression-free Survival (PFS)
    End point description
    Progression-free survival was defined as the time from randomization to the date of radiographic disease progression or death from any cause, whichever event occurred first. Participants without either event were censored on the date of their last disease assessment. Disease progression was based on the investigator’s assessment of scans using the version of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The analysis was conducted in the radiographic endpoint primary analysis set which included all participants in the primary analysis set who did not have disease progression prior to randomization.
    End point type
    Secondary
    End point timeframe
    From randomization until disease progression or death; maximum time on follow-up was 87.23 months.
    End point values
    		 Placebo Darbepoetin alfa
    Number of subjects analysed
    819
    1638
    Units: months
        median (confidence interval 95%)
    4.340 (4.170 to 4.700)
    4.800 (4.370 to 5.320)
    Statistical analysis title
    		 Primary Analysis of Progression-free Survival
    Statistical analysis description
    The primary analysis of PFS used a Cox Proportional Hazard Model stratified by the randomization stratification factors (geographic region, histology, and screening hemoglobin), with treatment group as the only covariate. A hazard ratio < 1.0 indicates a lower risk of death or progression for darbepoetin alfa relative to placebo.
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2457
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.04
    Notes
    [6] - If non-inferiority was declared for OS, non-inferiority would be declared for PFS if the upper confidence limit for the hazard ratio was less than 1.15 using a 1-sided significance level of 0.025.
    Statistical analysis title
    		 Sensitivity Analysis - Unstratified Model
    Statistical analysis description
    As a sensitivity analysis, an unstratified Cox Proportional Hazard Model with treatment group as the only covariate was conducted. A hazard ratio < 1.0 indicates a lower risk of death or progression for darbepoetin alfa relative to placebo.
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2457
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.04
    Notes
    [7] - If non-inferiority was declared for OS, non-inferiority would be declared for PFS if the upper confidence limit for the hazard ratio was less than 1.15 using a 1-sided significance level of 0.025.
    Statistical analysis title
    		 Superiority Analysis (Stratified)
    Statistical analysis description
    If non-inferiority was demonstrated for both OS and PFS and superiority was demonstrated for the transfusion endpoint, superiority was then tested for both OS and PFS using the Hochberg procedure to adjust for multiplicity.
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2457
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.31 [8]
    Method
    		 Stratified log-rank test
    Confidence interval
    Notes
    [8] - Stratified by the randomization stratification factors (geographic region, histology, screening hemoglobin).
    Statistical analysis title
    		 Superiority Analysis (Unstratified)
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2457
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.27 [9]
    Method
    		 Logrank
    Confidence interval
    Notes
    [9] - Unstratified log rank test
    Statistical analysis title
    		 PFS Adjusted for Cross-in
    Statistical analysis description
    To evaluate the potential effect of cross-in (participants in the placebo group who began treatment with an erythropoiesis-stimulating agent (ESA) at any point after randomization), a sensitivity analysis was conducted that included ESA use as a time-dependent covariate in a Cox regression model stratified by the randomization stratification factors (geographic region, histology, and screening hemoglobin).
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2457
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.05

    Secondary: Percentage of Participants with a Red Blood Cell Transfusion or Hemoglobin ≤ 8.0 g/dL From Week 5 to End of the Efficacy Treatment Period

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    End point title
    		 Percentage of Participants with a Red Blood Cell Transfusion or Hemoglobin ≤ 8.0 g/dL From Week 5 to End of the Efficacy Treatment Period
    End point description
    Any red blood cell (RBC) transfusion (packed RBCs or whole blood) given or a hemoglobin ≥ 8.0 g/dL on or after study day 29 until the EOETP, inclusive. The analysis was conducted in primary analysis set participants who were on study as of day 29.
    End point type
    Secondary
    End point timeframe
    Week 5 (day 29) to end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); median (range) duration of dosing was 10 (1 to 106) weeks in both groups.
    End point values
    		 Placebo Darbepoetin alfa
    Number of subjects analysed
    764
    1517
    Units: percentage of participants
        number (not applicable)
    29.2
    22.5
    Statistical analysis title
    		 Analysis of Transfusion or Hemoglobin ≤ 8.0 g/dL
    Statistical analysis description
    The primary analysis of the incidence of a transfusion or hemoglobin ≤ 8.0 g/dL from day 29 to EOETP was based on the Cochran-Mantel-Haenszel method to test for treatment group differences while adjusting for the randomization stratification factors (geographic region, histology, and screening hemoglobin). An odds ratio < 1.0 indicates a lower event rate for darbepoetin alfa relative to placebo.
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2281
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.704
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.573
         upper limit
    		 0.864
    Notes
    [10] - If non-inferiority was declared for OS and PFS, superiority would be declared for the transfusion endpoint if the p-value from a two-sided test of significance using the Cochran-Mantel-Haenszel method was less than 0.05 in favor of the darbepoetin alfa group.
    Statistical analysis title
    		 Sensitivity Analysis - Logistic Regression
    Statistical analysis description
    As a sensitivity analysis a logistic regression analysis was conducted, stratified by the randomization stratification factors (geographic region, histology, screening hemoglobin). An odds ratio < 1.0 indicates a lower event rate for darbepoetin alfa relative to placebo.
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2281
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.705
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.574
         upper limit
    		 0.866

    Secondary: Number of Participants with Adverse Events of Special Interest

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    End point title
    		 Number of Participants with Adverse Events of Special Interest
    End point description
    Adverse events of interest for darbepoetin alfa, based on clinical data in anemic patients with cancer to date, included the following categories: antibody-mediated pure red cell aplasia (PRCA), cardiac failure, central nervous system vascular disorders, convulsions, embolic and thrombotic events, hypersensitivity, hypertension, ischemic heart disease, malignancies, and severe cutaneous adverse reactions. Lack of efficacy and medication errors were also evaluated. The analysis was conducted in all randomized and consented participants who received at least 1 dose of study drug. Four participants in the placebo group received at least 1 dose of darbepoetin alfa during the study and were included in the darbepoetin alfa group for safety analyses.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug until 30 days after last dose; the median (range) duration of treatment was 10 (1 to 106) weeks in both groups.
    End point values
    		 Placebo Darbepoetin alfa
    Number of subjects analysed
    833
    1685
    Units: participants
        Any adverse events of interest
    157
    369
        Antibody-mediated pure red cell aplasia
    20
    51
        Cardiac failure
    7
    12
        Central nervous system vascular disorders
    8
    25
        Convulsions
    8
    9
        Embolic and thrombotic events
    34
    89
        Embolic and thrombotic events, arterial
    6
    19
        Embolic and thrombotic events, venous
    23
    51
        Embolic and thrombotic events, unspecified/mixed
    10
    26
        Hypersensitivity
    75
    178
        Hypertension
    26
    41
        Ischaemic heart disease
    9
    23
        Lack of efficacy/effect
    0
    0
        Malignancies
    16
    38
        Medication errors
    0
    1
        Severe cutaneous adverse reactions
    11
    35
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an Objective Tumor Response

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    End point title
    		 Percentage of Participants with an Objective Tumor Response
    End point description
    Objective response was defined as the incidence of a complete or partial response at any time during the study. Response was determined by the investigator’s assessment of the scans using RECIST version 1.0 or 1.1 depending on the timing of enrollment. The analysis was conducted in the radiographic endpoint primary analysis set which included all participants in the primary analysis set who did not have disease progression prior to randomization.
    End point type
    Secondary
    End point timeframe
    Day 1 to end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); median (range) duration of dosing was 10 (1 to 106) weeks in both groups.
    End point values
    		 Placebo Darbepoetin alfa
    Number of subjects analysed
    819
    1638
    Units: percentage of participants
        number (not applicable)
    32.6
    36.2
    Statistical analysis title
    		 Stratified Analysis of Objective Response
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2457
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.076 [11]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.173
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.983
         upper limit
    		 1.401
    Notes
    [11] - Cochran-Mantel-Haenszel method adjusted for the randomization stratification factors (geographic region, histology, screening hemoglobin).
    Statistical analysis title
    		 Unstratified Analysis of Objective Response
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2457
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.078 [12]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.173
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.982
         upper limit
    		 1.401
    Notes
    [12] - Unstratified analysis

    Secondary: Number of Participants who Developed Neutralizing Antibodies to Darbepoetin Alfa

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    End point title
    		 Number of Participants who Developed Neutralizing Antibodies to Darbepoetin Alfa
    End point description
    Developing antibody incidence was defined as neutralizing antibody positive postbaseline with a negative or no result at baseline. The analysis was conducted in all randomized and consented participants who received at least one dose of study drug and with a postbaseline result.
    End point type
    Secondary
    End point timeframe
    Baseline and end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later. the median (range) duration of treatment was 10 (1 to 106) weeks in both groups.
    End point values
    		 Placebo Darbepoetin alfa
    Number of subjects analysed
    803
    1606
    Units: participants
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Red Blood Cell Transfusion or Hemoglobin ≤ 8.0 g/dL From Week 1 to End of the Efficacy Treatment Period

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    End point title
    		 Percentage of Participants with a Red Blood Cell Transfusion or Hemoglobin ≤ 8.0 g/dL From Week 1 to End of the Efficacy Treatment Period
    End point description
    Any red blood cell (RBC) transfusion (packed RBCs or whole blood) given or a hemoglobin ≤ 8.0 g/dL on or after study day 1 until the EOETP, inclusive. The analysis was conducted in the primary analysis set.
    End point type
    Secondary
    End point timeframe
    Week 1 to end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); the median (range) duration of treatment was 10 (1 to 106) weeks in both groups.
    End point values
    		 Placebo Darbepoetin alfa
    Number of subjects analysed
    836
    1680
    Units: percentage of participants
        number (not applicable)
    29.7
    24.2
    Statistical analysis title
    		 Stratified Analysis
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2516
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.003 [13]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.741
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 0.901
    Notes
    [13] - Cochran-Mantel-Haenszel method adjusted for the randomization stratification factors (geographic region, histology, screening hemoglobin).
    Statistical analysis title
    		 Unstratified Analysis
    Comparison groups
    Placebo v Darbepoetin alfa
    Number of subjects included in analysis
    2516
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.003
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.758
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 0.913

    Secondary: Change from Baseline in Hemoglobin to End of Efficacy Treatment Period

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    End point title
    		 Change from Baseline in Hemoglobin to End of Efficacy Treatment Period
    End point description
    Post-baseline hemoglobin values within 28 days after a RBC transfusion were not be used in the calculation of change. The analysis was conducted in the primary analysis set with available baseline and at least 1 postbaseline value; if the EOETP value was missing, the last available postbaseline value was used.
    End point type
    Secondary
    End point timeframe
    Baseline and end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of study drug or the last dose of chemotherapy, whichever was later); the median (range) duration of treatment was 10 (1 to 106) weeks in both groups.
    End point values
    		 Placebo Darbepoetin alfa
    Number of subjects analysed
    633
    1344
    Units: g/dL
        arithmetic mean (standard deviation)
    -0.11 ± 1.71
    0.50 ± 1.81
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until 30 days after last dose; the median (range) duration of treatment was 10 (1 to 106) weeks in both groups.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.

    Reporting group title
    Darbepoetin Alfa
    Reporting group description
    		 Participants received darbepoetin alfa 500 µg once every 3 weeks (Q3W) administered subcutaneously until 3 weeks after the completion of chemotherapy or upon determination of disease progression, whichever occurred first.

    Serious adverse events
    		 Placebo Darbepoetin Alfa
    Total subjects affected by serious adverse events
         subjects affected / exposed
    259 / 833 (31.09%)
    524 / 1685 (31.10%)
         number of deaths (all causes)
    657
    1273
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma stage IV
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Malignant pleural effusion
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to adrenals
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to bone
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Non-small cell lung cancer
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Tumour associated fever
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Accelerated hypertension
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    3 / 833 (0.36%)
    11 / 1685 (0.65%)
         occurrences causally related to treatment / all
    1 / 3
    6 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Extremity necrosis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    6 / 833 (0.72%)
    3 / 1685 (0.18%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Hypovolaemic shock
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Peripheral embolism
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior vena cava occlusion
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superior vena cava syndrome
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicose ulceration
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular occlusion
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Lymphadenectomy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroidectomy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         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
         subjects affected / exposed
    7 / 833 (0.84%)
    11 / 1685 (0.65%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 12
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Chest pain
         subjects affected / exposed
    2 / 833 (0.24%)
    5 / 1685 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    9 / 833 (1.08%)
    12 / 1685 (0.71%)
         occurrences causally related to treatment / all
    0 / 9
    1 / 12
         deaths causally related to treatment / all
    0 / 9
    1 / 12
    Disease progression
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Fatigue
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    2 / 833 (0.24%)
    3 / 1685 (0.18%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Inflammation
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    4 / 833 (0.48%)
    7 / 1685 (0.42%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 4
    0 / 7
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 833 (0.00%)
    5 / 1685 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Organ failure
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pain
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Performance status decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 833 (0.36%)
    15 / 1685 (0.89%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 15
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Sudden death
         subjects affected / exposed
    8 / 833 (0.96%)
    12 / 1685 (0.71%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 12
         deaths causally related to treatment / all
    1 / 8
    0 / 12
    Swelling
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transfusion associated graft versus host disease
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         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
    Acute pulmonary oedema
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    2 / 833 (0.24%)
    9 / 1685 (0.53%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 9
         deaths causally related to treatment / all
    0 / 2
    0 / 6
    Aspiration
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Asthma
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial haemorrhage
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Bronchitis chronic
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cough
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    26 / 833 (3.12%)
    31 / 1685 (1.84%)
         occurrences causally related to treatment / all
    0 / 34
    1 / 33
         deaths causally related to treatment / all
    0 / 12
    0 / 11
    Dyspnoea exertional
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Epistaxis
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    3 / 833 (0.36%)
    14 / 1685 (0.83%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 6
    Hypoxia
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagobronchial fistula
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Painful respiration
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    12 / 833 (1.44%)
    6 / 1685 (0.36%)
         occurrences causally related to treatment / all
    1 / 16
    0 / 6
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 833 (0.00%)
    4 / 1685 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Pneumonitis
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary artery thrombosis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    6 / 833 (0.72%)
    20 / 1685 (1.19%)
         occurrences causally related to treatment / all
    2 / 8
    9 / 22
         deaths causally related to treatment / all
    1 / 3
    3 / 11
    Pulmonary haemorrhage
         subjects affected / exposed
    2 / 833 (0.24%)
    5 / 1685 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Pulmonary hypertension
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory acidosis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory depression
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory distress
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Respiratory failure
         subjects affected / exposed
    13 / 833 (1.56%)
    24 / 1685 (1.42%)
         occurrences causally related to treatment / all
    1 / 14
    2 / 29
         deaths causally related to treatment / all
    1 / 9
    1 / 21
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood albumin abnormal
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood pressure increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Eastern Cooperative Oncology Group performance status worsened
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoglobin abnormal
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Platelet count decreased
         subjects affected / exposed
    6 / 833 (0.72%)
    6 / 1685 (0.36%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salmonella test positive
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Laceration
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nerve root injury lumbar
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Poisoning
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Procedural pneumothorax
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation dysphagia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation pneumonitis
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Acute myocardial infarction
         subjects affected / exposed
    3 / 833 (0.36%)
    5 / 1685 (0.30%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    Angina pectoris
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    3 / 833 (0.36%)
    8 / 1685 (0.47%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    2 / 833 (0.24%)
    7 / 1685 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 7
    Cardiac failure
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure acute
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure congestive
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    7 / 833 (0.84%)
    9 / 1685 (0.53%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 9
         deaths causally related to treatment / all
    0 / 7
    0 / 8
    Cardio-respiratory distress
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cardiogenic shock
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiopulmonary failure
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Cardiovascular insufficiency
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 833 (0.12%)
    5 / 1685 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Myocardial ischaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nodal arrhythmia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Sinus node dysfunction
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    Cerebellar infarction
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 833 (0.00%)
    4 / 1685 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Cerebral ischaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Cognitive disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dementia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Diabetic neuropathy
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Epilepsy
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial nerve disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Headache
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiplegia
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraplegia
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 833 (0.24%)
    4 / 1685 (0.24%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Somnolence
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stroke in evolution
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Syncope
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombotic cerebral infarction
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Thrombotic stroke
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 833 (0.00%)
    4 / 1685 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Unresponsive to stimuli
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         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
         subjects affected / exposed
    46 / 833 (5.52%)
    57 / 1685 (3.38%)
         occurrences causally related to treatment / all
    2 / 60
    1 / 65
         deaths causally related to treatment / all
    1 / 2
    0 / 1
    Bicytopenia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    8 / 833 (0.96%)
    20 / 1685 (1.19%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 23
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    7 / 833 (0.84%)
    14 / 1685 (0.83%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic anaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    2 / 833 (0.24%)
    7 / 1685 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    6 / 833 (0.72%)
    17 / 1685 (1.01%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    4 / 833 (0.48%)
    9 / 1685 (0.53%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sideroblastic anaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    16 / 833 (1.92%)
    28 / 1685 (1.66%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 34
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Thrombocytosis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Angle closure glaucoma
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 833 (0.00%)
    12 / 1685 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 833 (0.00%)
    4 / 1685 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    8 / 833 (0.96%)
    12 / 1685 (0.71%)
         occurrences causally related to treatment / all
    1 / 8
    1 / 14
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dysphagia
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faeces discoloured
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Gastrointestinal motility disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nausea
         subjects affected / exposed
    2 / 833 (0.24%)
    3 / 1685 (0.18%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrotising colitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic colitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal ulcer
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 833 (0.24%)
    9 / 1685 (0.53%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Peau d'orange
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    4 / 833 (0.48%)
    12 / 1685 (0.71%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 4
    Azotaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstructive uropathy
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    2 / 833 (0.24%)
    5 / 1685 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Urinary retention
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vesical fistula
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toxic nodular goitre
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    3 / 833 (0.36%)
    3 / 1685 (0.18%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Groin pain
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis of jaw
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    4 / 833 (0.48%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bronchitis
         subjects affected / exposed
    3 / 833 (0.36%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometritis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Furuncle
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 833 (0.24%)
    7 / 1685 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 833 (0.00%)
    4 / 1685 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung abscess
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    7 / 833 (0.84%)
    13 / 1685 (0.77%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 16
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    20 / 833 (2.40%)
    44 / 1685 (2.61%)
         occurrences causally related to treatment / all
    0 / 26
    0 / 56
         deaths causally related to treatment / all
    0 / 5
    0 / 9
    Pneumonia bacterial
         subjects affected / exposed
    1 / 833 (0.12%)
    6 / 1685 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory tract infection
         subjects affected / exposed
    4 / 833 (0.48%)
    6 / 1685 (0.36%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Sepsis
         subjects affected / exposed
    9 / 833 (1.08%)
    15 / 1685 (0.89%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 22
         deaths causally related to treatment / all
    0 / 4
    0 / 9
    Septic encephalopathy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Staphylococcal infection
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superinfection viral
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    4 / 833 (0.48%)
    6 / 1685 (0.36%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cachexia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    1 / 833 (0.12%)
    7 / 1685 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dehydration
         subjects affected / exposed
    5 / 833 (0.60%)
    6 / 1685 (0.36%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Failure to thrive
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    4 / 833 (0.48%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperuricaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    5 / 1685 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    3 / 833 (0.36%)
    2 / 1685 (0.12%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypophagia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoproteinaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo Darbepoetin Alfa
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    674 / 833 (80.91%)
    1319 / 1685 (78.28%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain
         subjects affected / exposed
    1 / 833 (0.12%)
    8 / 1685 (0.47%)
         occurrences all number
    1
    8
    Malignant pleural effusion
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Metastases to central nervous system
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Paraneoplastic syndrome
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Tumour haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Tumour pain
         subjects affected / exposed
    2 / 833 (0.24%)
    6 / 1685 (0.36%)
         occurrences all number
    2
    6
    Uterine leiomyoma
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Vascular disorders
    Angiopathy
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Arterial disorder
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Arteriosclerosis
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Deep vein thrombosis
         subjects affected / exposed
    7 / 833 (0.84%)
    8 / 1685 (0.47%)
         occurrences all number
    7
    8
    Diastolic hypertension
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Embolism
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Extremity necrosis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Flushing
         subjects affected / exposed
    0 / 833 (0.00%)
    4 / 1685 (0.24%)
         occurrences all number
    0
    4
    Haematoma
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    2
    2
    Haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Hot flush
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    4
    1
    Hypertension
         subjects affected / exposed
    21 / 833 (2.52%)
    35 / 1685 (2.08%)
         occurrences all number
    32
    43
    Hypotension
         subjects affected / exposed
    6 / 833 (0.72%)
    11 / 1685 (0.65%)
         occurrences all number
    6
    15
    Intermittent claudication
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Orthostatic hypotension
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Pallor
         subjects affected / exposed
    2 / 833 (0.24%)
    3 / 1685 (0.18%)
         occurrences all number
    2
    3
    Pelvic venous thrombosis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Peripheral venous disease
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Phlebitis
         subjects affected / exposed
    1 / 833 (0.12%)
    5 / 1685 (0.30%)
         occurrences all number
    1
    5
    Phlebitis superficial
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Superior vena cava syndrome
         subjects affected / exposed
    2 / 833 (0.24%)
    3 / 1685 (0.18%)
         occurrences all number
    2
    3
    Thrombophlebitis
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    4
    Thrombophlebitis superficial
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Thrombosis
         subjects affected / exposed
    0 / 833 (0.00%)
    5 / 1685 (0.30%)
         occurrences all number
    0
    5
    Varicose vein
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Vena cava thrombosis
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Vascular insufficiency
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Surgical and medical procedures
    Cataract operation
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Constipation prophylaxis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Joint arthroplasty
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Leg amputation
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Pneumonolysis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Reduction of increased intracranial pressure
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Asthenia
         subjects affected / exposed
    92 / 833 (11.04%)
    158 / 1685 (9.38%)
         occurrences all number
    111
    200
    Axillary pain
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Catheter site haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Catheter site pain
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    4
    Chest discomfort
         subjects affected / exposed
    2 / 833 (0.24%)
    5 / 1685 (0.30%)
         occurrences all number
    4
    6
    Chest pain
         subjects affected / exposed
    30 / 833 (3.60%)
    52 / 1685 (3.09%)
         occurrences all number
    39
    60
    Chills
         subjects affected / exposed
    5 / 833 (0.60%)
    9 / 1685 (0.53%)
         occurrences all number
    5
    9
    Complication associated with device
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Extravasation
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Face oedema
         subjects affected / exposed
    2 / 833 (0.24%)
    5 / 1685 (0.30%)
         occurrences all number
    3
    5
    Facial pain
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Fatigue
         subjects affected / exposed
    69 / 833 (8.28%)
    117 / 1685 (6.94%)
         occurrences all number
    96
    154
    Feeling abnormal
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Feeling cold
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Gait disturbance
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences all number
    1
    4
    General physical health deterioration
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Generalised oedema
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Gravitational oedema
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hyperthermia
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Implant site pain
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Inflammation
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    3
    Influenza like illness
         subjects affected / exposed
    2 / 833 (0.24%)
    3 / 1685 (0.18%)
         occurrences all number
    2
    3
    Infusion site extravasation
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Injection site haematoma
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Injection site phlebitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Injection site reaction
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Local swelling
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Localised oedema
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    2
    2
    Malaise
         subjects affected / exposed
    6 / 833 (0.72%)
    14 / 1685 (0.83%)
         occurrences all number
    6
    16
    Mass
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Mucosal inflammation
         subjects affected / exposed
    8 / 833 (0.96%)
    7 / 1685 (0.42%)
         occurrences all number
    9
    9
    Mucous membrane disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Non-cardiac chest pain
         subjects affected / exposed
    7 / 833 (0.84%)
    23 / 1685 (1.36%)
         occurrences all number
    8
    24
    Oedema
         subjects affected / exposed
    7 / 833 (0.84%)
    10 / 1685 (0.59%)
         occurrences all number
    7
    11
    Oedema peripheral
         subjects affected / exposed
    30 / 833 (3.60%)
    50 / 1685 (2.97%)
         occurrences all number
    39
    61
    Pain
         subjects affected / exposed
    18 / 833 (2.16%)
    41 / 1685 (2.43%)
         occurrences all number
    20
    49
    Performance status decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Peripheral swelling
         subjects affected / exposed
    5 / 833 (0.60%)
    5 / 1685 (0.30%)
         occurrences all number
    5
    6
    Pyrexia
         subjects affected / exposed
    57 / 833 (6.84%)
    110 / 1685 (6.53%)
         occurrences all number
    77
    136
    Temperature intolerance
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Vessel puncture site pain
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Vessel puncture site swelling
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Contrast media allergy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Drug hypersensitivity
         subjects affected / exposed
    5 / 833 (0.60%)
    2 / 1685 (0.12%)
         occurrences all number
    5
    3
    Hypersensitivity
         subjects affected / exposed
    1 / 833 (0.12%)
    8 / 1685 (0.47%)
         occurrences all number
    1
    8
    Immune system disorder
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Immunodeficiency
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Iodine allergy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Seasonal allergy
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    3
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Breast mass
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Breast pain
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    3
    0
    Breast swelling
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Menorrhagia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Pelvic pain
         subjects affected / exposed
    3 / 833 (0.36%)
    0 / 1685 (0.00%)
         occurrences all number
    3
    0
    Postmenopausal haemorrhage
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Prostatitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Scrotal oedema
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Vulvovaginal pruritus
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Allergic respiratory symptom
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Apnoea
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Aspiration
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Asthma
         subjects affected / exposed
    2 / 833 (0.24%)
    3 / 1685 (0.18%)
         occurrences all number
    2
    3
    Atelectasis
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Bronchial haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Bronchial hyperreactivity
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Bronchial obstruction
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Bronchiectasis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Bronchitis chronic
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Bronchospasm
         subjects affected / exposed
    2 / 833 (0.24%)
    5 / 1685 (0.30%)
         occurrences all number
    2
    5
    Bronchostenosis
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 833 (0.12%)
    9 / 1685 (0.53%)
         occurrences all number
    1
    9
    Cough
         subjects affected / exposed
    52 / 833 (6.24%)
    147 / 1685 (8.72%)
         occurrences all number
    56
    170
    Dry throat
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Dysphonia
         subjects affected / exposed
    4 / 833 (0.48%)
    12 / 1685 (0.71%)
         occurrences all number
    4
    12
    Dyspnoea
         subjects affected / exposed
    60 / 833 (7.20%)
    111 / 1685 (6.59%)
         occurrences all number
    76
    138
    Dyspnoea at rest
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea exertional
         subjects affected / exposed
    8 / 833 (0.96%)
    21 / 1685 (1.25%)
         occurrences all number
    9
    23
    Epistaxis
         subjects affected / exposed
    11 / 833 (1.32%)
    31 / 1685 (1.84%)
         occurrences all number
    11
    38
    Haemoptysis
         subjects affected / exposed
    24 / 833 (2.88%)
    42 / 1685 (2.49%)
         occurrences all number
    30
    55
    Hiccups
         subjects affected / exposed
    1 / 833 (0.12%)
    7 / 1685 (0.42%)
         occurrences all number
    1
    7
    Hypopnoea
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hypoxia
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    2
    3
    Laryngeal inflammation
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Laryngeal pain
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Lung infiltration
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Nasal congestion
         subjects affected / exposed
    3 / 833 (0.36%)
    5 / 1685 (0.30%)
         occurrences all number
    3
    5
    Nasal dryness
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Nasal mucosal ulcer
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    7 / 833 (0.84%)
    15 / 1685 (0.89%)
         occurrences all number
    7
    15
    Orthopnoea
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Paranasal sinus hypersecretion
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Pleural effusion
         subjects affected / exposed
    4 / 833 (0.48%)
    8 / 1685 (0.47%)
         occurrences all number
    13
    9
    Pleurisy
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Pleuritic pain
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    3
    Pneumonitis
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    1
    Pneumothorax
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Productive cough
         subjects affected / exposed
    15 / 833 (1.80%)
    31 / 1685 (1.84%)
         occurrences all number
    16
    35
    Pulmonary arterial hypertension
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Pulmonary congestion
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Pulmonary embolism
         subjects affected / exposed
    2 / 833 (0.24%)
    7 / 1685 (0.42%)
         occurrences all number
    2
    7
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Pulmonary mass
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Pulmonary oedema
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Respiratory disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Respiratory distress
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Respiratory failure
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Respiratory tract congestion
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Respiratory tract haemorrhage
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    1
    Rhinorrhoea
         subjects affected / exposed
    3 / 833 (0.36%)
    6 / 1685 (0.36%)
         occurrences all number
    5
    7
    Sinus congestion
         subjects affected / exposed
    1 / 833 (0.12%)
    6 / 1685 (0.36%)
         occurrences all number
    1
    6
    Sinus disorder
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Sneezing
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    1
    Sputum discoloured
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Sputum retention
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    1
    Tachypnoea
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Tonsillar hypertrophy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Wheezing
         subjects affected / exposed
    2 / 833 (0.24%)
    4 / 1685 (0.24%)
         occurrences all number
    2
    4
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Anxiety
         subjects affected / exposed
    9 / 833 (1.08%)
    18 / 1685 (1.07%)
         occurrences all number
    9
    18
    Anxiety disorder
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Anxiety disorder due to a general medical condition
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Confusional state
         subjects affected / exposed
    4 / 833 (0.48%)
    6 / 1685 (0.36%)
         occurrences all number
    5
    7
    Delirium
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Depressed mood
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Depression
         subjects affected / exposed
    8 / 833 (0.96%)
    11 / 1685 (0.65%)
         occurrences all number
    8
    11
    Dysphoria
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Flight of ideas
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hallucination
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hyposomnia
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    3
    Initial insomnia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Insomnia
         subjects affected / exposed
    22 / 833 (2.64%)
    41 / 1685 (2.43%)
         occurrences all number
    26
    45
    Insomnia related to another mental condition
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Mental disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Mental status changes
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    3
    Mood swings
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Organic brain syndrome
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Restlessness
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Sleep disorder
         subjects affected / exposed
    3 / 833 (0.36%)
    1 / 1685 (0.06%)
         occurrences all number
    4
    1
    Tic
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Product issues
    Device leakage
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    1
    Chronic hepatic failure
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    4
    Drug-induced liver injury
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Gallbladder polyp
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Hepatic cyst
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Hepatic failure
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hepatic function abnormal
         subjects affected / exposed
    4 / 833 (0.48%)
    9 / 1685 (0.53%)
         occurrences all number
    5
    10
    Hepatic lesion
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Hepatic pain
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Hepatic steatosis
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Hepatotoxicity
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Hyperbilirubinaemia
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences all number
    2
    2
    Hyperplastic cholecystopathy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Liver disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Liver injury
         subjects affected / exposed
    3 / 833 (0.36%)
    4 / 1685 (0.24%)
         occurrences all number
    3
    5
    Ocular icterus
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Investigations
    Alanine aminotransferase
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Alanine aminotransferase decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    3
    Alanine aminotransferase increased
         subjects affected / exposed
    26 / 833 (3.12%)
    43 / 1685 (2.55%)
         occurrences all number
    47
    57
    Albumin CSF decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Alpha hydroxybutyrate dehydrogenase increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Antineutrophil cytoplasmic antibody decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Aspartate aminotransferase decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    21 / 833 (2.52%)
    38 / 1685 (2.26%)
         occurrences all number
    34
    51
    Aspiration pleural cavity
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Biopsy pleura
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Blood albumin decreased
         subjects affected / exposed
    5 / 833 (0.60%)
    7 / 1685 (0.42%)
         occurrences all number
    6
    7
    Blood alkaline phosphatase increased
         subjects affected / exposed
    7 / 833 (0.84%)
    20 / 1685 (1.19%)
         occurrences all number
    9
    24
    Blood bicarbonate decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Blood bicarbonate increased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    8
    Blood bilirubin unconjugated increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Blood calcitonin increased
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Blood calcium decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    2
    Blood chloride decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Blood chloride increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Blood cholesterol increased
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Blood creatine
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Blood creatine abnormal
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    3
    Blood creatine increased
         subjects affected / exposed
    0 / 833 (0.00%)
    6 / 1685 (0.36%)
         occurrences all number
    0
    7
    Blood creatine phosphokinase MB increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Blood creatinine
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    16 / 833 (1.92%)
    27 / 1685 (1.60%)
         occurrences all number
    19
    43
    Blood glucose increased
         subjects affected / exposed
    5 / 833 (0.60%)
    6 / 1685 (0.36%)
         occurrences all number
    7
    11
    Blood iron abnormal
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Blood iron decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    8 / 833 (0.96%)
    13 / 1685 (0.77%)
         occurrences all number
    8
    15
    Blood potassium decreased
         subjects affected / exposed
    2 / 833 (0.24%)
    6 / 1685 (0.36%)
         occurrences all number
    2
    8
    Blood pressure increased
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences all number
    4
    3
    Blood pressure systolic increased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Blood testosterone decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Blood triglycerides increased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Blood urea decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Blood urea increased
         subjects affected / exposed
    6 / 833 (0.72%)
    10 / 1685 (0.59%)
         occurrences all number
    8
    10
    Blood uric acid increased
         subjects affected / exposed
    2 / 833 (0.24%)
    4 / 1685 (0.24%)
         occurrences all number
    2
    4
    Body temperature increased
         subjects affected / exposed
    3 / 833 (0.36%)
    1 / 1685 (0.06%)
         occurrences all number
    4
    1
    Brain natriuretic peptide increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Breath sounds abnormal
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    1
    C-reactive protein increased
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Creatinine renal clearance decreased
         subjects affected / exposed
    2 / 833 (0.24%)
    3 / 1685 (0.18%)
         occurrences all number
    3
    5
    Creatinine renal clearance increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Eastern Cooperative Oncology Group performance status worsened
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences all number
    1
    5
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Fibrin D dimer increased
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Fibrin degradation products increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Gamma-glutamyltransferase
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Gamma-glutamyltransferase decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    10 / 833 (1.20%)
    22 / 1685 (1.31%)
         occurrences all number
    15
    33
    Gastric pH decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    General physical condition abnormal
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Globulins decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Glomerular filtration rate decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Glucose tolerance decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Glucose urine present
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Glycosylated haemoglobin increased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Granulocyte count decreased
         subjects affected / exposed
    2 / 833 (0.24%)
    9 / 1685 (0.53%)
         occurrences all number
    6
    15
    Haematocrit decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Haemoglobin decreased
         subjects affected / exposed
    10 / 833 (1.20%)
    8 / 1685 (0.47%)
         occurrences all number
    15
    12
    Heart rate increased
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    2
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Human epidermal growth factor receptor decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    International normalised ratio increased
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    4
    1
    Iron binding capacity total decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Iron binding capacity unsaturated decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Laboratory test abnormal
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Liver function test abnormal
         subjects affected / exposed
    1 / 833 (0.12%)
    10 / 1685 (0.59%)
         occurrences all number
    1
    13
    Liver function test increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Lymphocyte count abnormal
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    5 / 833 (0.60%)
    15 / 1685 (0.89%)
         occurrences all number
    11
    33
    Lymphocyte count increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    3
    Mean cell volume increased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Monocyte percentage increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Myoglobin blood increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Neutrophil count
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Neutrophil count abnormal
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    4
    2
    Neutrophil count decreased
         subjects affected / exposed
    47 / 833 (5.64%)
    95 / 1685 (5.64%)
         occurrences all number
    107
    249
    Neutrophil count increased
         subjects affected / exposed
    0 / 833 (0.00%)
    5 / 1685 (0.30%)
         occurrences all number
    0
    6
    Neutrophil percentage increased
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    PCO2 decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Platelet adhesiveness decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Platelet adhesiveness increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Platelet count abnormal
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Platelet count decreased
         subjects affected / exposed
    66 / 833 (7.92%)
    130 / 1685 (7.72%)
         occurrences all number
    126
    282
    Protein total decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Platelet count increased
         subjects affected / exposed
    2 / 833 (0.24%)
    3 / 1685 (0.18%)
         occurrences all number
    2
    4
    Protein total increased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Protein urine present
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Respiratory rate decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Serum ferritin decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Serum ferritin increased
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Transaminases increased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Troponin I increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Troponin increased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Urine output decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Vitamin D decreased
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Weight decreased
         subjects affected / exposed
    24 / 833 (2.88%)
    53 / 1685 (3.15%)
         occurrences all number
    26
    59
    Weight increased
         subjects affected / exposed
    4 / 833 (0.48%)
    4 / 1685 (0.24%)
         occurrences all number
    4
    4
    White blood cell count
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    3
    1
    White blood cell count decreased
         subjects affected / exposed
    64 / 833 (7.68%)
    138 / 1685 (8.19%)
         occurrences all number
    197
    407
    White blood cell count increased
         subjects affected / exposed
    3 / 833 (0.36%)
    7 / 1685 (0.42%)
         occurrences all number
    3
    9
    White blood cells urine positive
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Airway complication of anaesthesia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Animal scratch
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Ankle fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Arthropod bite
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Chemical poisoning
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Clavicle fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Concussion
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Contusion
         subjects affected / exposed
    5 / 833 (0.60%)
    6 / 1685 (0.36%)
         occurrences all number
    5
    6
    Fall
         subjects affected / exposed
    3 / 833 (0.36%)
    7 / 1685 (0.42%)
         occurrences all number
    3
    7
    Fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Humerus fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Infusion related reaction
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Laceration
         subjects affected / exposed
    2 / 833 (0.24%)
    3 / 1685 (0.18%)
         occurrences all number
    2
    3
    Limb injury
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Overdose
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Poisoning
         subjects affected / exposed
    4 / 833 (0.48%)
    4 / 1685 (0.24%)
         occurrences all number
    5
    4
    Post procedural fistula
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Procedural pain
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Radiation oesophagitis
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Radiation pneumonitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Radiation skin injury
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Rib fracture
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Skin abrasion
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Spinal compression fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Tooth fracture
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Toxicity to various agents
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Upper limb fracture
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Wound
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Wound complication
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Congenital, familial and genetic disorders
    Aplasia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Angina pectoris
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    3
    Angina unstable
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Arrhythmia
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences all number
    2
    2
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences all number
    2
    4
    Atrial tachycardia
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Cardiac discomfort
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Cardiac disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Cardiac failure
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    1
    Cardiac failure congestive
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Cardiomyopathy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Congestive cardiomyopathy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Cyanosis
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Metabolic cardiomyopathy
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Myocardial infarction
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Myocardial ischaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Palpitations
         subjects affected / exposed
    2 / 833 (0.24%)
    4 / 1685 (0.24%)
         occurrences all number
    3
    4
    Pericardial effusion
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Pericarditis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Sinus arrhythmia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Sinus tachycardia
         subjects affected / exposed
    1 / 833 (0.12%)
    5 / 1685 (0.30%)
         occurrences all number
    1
    5
    Supraventricular extrasystoles
         subjects affected / exposed
    2 / 833 (0.24%)
    3 / 1685 (0.18%)
         occurrences all number
    2
    3
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Tachycardia
         subjects affected / exposed
    7 / 833 (0.84%)
    10 / 1685 (0.59%)
         occurrences all number
    8
    10
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Anaesthesia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Aphasia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Aphonia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Ataxia
         subjects affected / exposed
    2 / 833 (0.24%)
    5 / 1685 (0.30%)
         occurrences all number
    2
    5
    Burning sensation
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Central nervous system lesion
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Central pain syndrome
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Cerebral atrophy
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Cerebral infarction
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Cerebral ischaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Cerebrovascular disorder
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Cognitive disorder
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Diabetic neuropathy
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Dizziness
         subjects affected / exposed
    24 / 833 (2.88%)
    58 / 1685 (3.44%)
         occurrences all number
    26
    67
    Dizziness postural
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Dysarthria
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Dysgeusia
         subjects affected / exposed
    2 / 833 (0.24%)
    7 / 1685 (0.42%)
         occurrences all number
    2
    7
    Dyskinesia
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Encephalopathy
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Epilepsy
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Facial paralysis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Head discomfort
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Headache
         subjects affected / exposed
    18 / 833 (2.16%)
    55 / 1685 (3.26%)
         occurrences all number
    20
    61
    Hemiparesis
         subjects affected / exposed
    2 / 833 (0.24%)
    4 / 1685 (0.24%)
         occurrences all number
    2
    4
    Hemiplegia
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Hypoaesthesia
         subjects affected / exposed
    13 / 833 (1.56%)
    21 / 1685 (1.25%)
         occurrences all number
    16
    23
    Hypogeusia
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences all number
    2
    2
    Intellectual disability
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Intercostal neuralgia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Lethargy
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    5
    Loss of consciousness
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Migraine
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Monoparesis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Nervous system disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Neuralgia
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    3
    Neuropathy peripheral
         subjects affected / exposed
    40 / 833 (4.80%)
    57 / 1685 (3.38%)
         occurrences all number
    51
    69
    Paraesthesia
         subjects affected / exposed
    14 / 833 (1.68%)
    26 / 1685 (1.54%)
         occurrences all number
    18
    36
    Peripheral motor neuropathy
         subjects affected / exposed
    3 / 833 (0.36%)
    4 / 1685 (0.24%)
         occurrences all number
    3
    8
    Peripheral sensory neuropathy
         subjects affected / exposed
    21 / 833 (2.52%)
    39 / 1685 (2.31%)
         occurrences all number
    30
    57
    Polyneuropathy
         subjects affected / exposed
    5 / 833 (0.60%)
    6 / 1685 (0.36%)
         occurrences all number
    6
    22
    Poor quality sleep
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Presyncope
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Psychomotor hyperactivity
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Sciatica
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Seizure
         subjects affected / exposed
    3 / 833 (0.36%)
    4 / 1685 (0.24%)
         occurrences all number
    3
    5
    Sensory disturbance
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Somnolence
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences all number
    1
    4
    Syncope
         subjects affected / exposed
    3 / 833 (0.36%)
    10 / 1685 (0.59%)
         occurrences all number
    3
    10
    Tremor
         subjects affected / exposed
    2 / 833 (0.24%)
    4 / 1685 (0.24%)
         occurrences all number
    2
    4
    Blood and lymphatic system disorders
    Agranulocytosis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Anaemia
         subjects affected / exposed
    244 / 833 (29.29%)
    451 / 1685 (26.77%)
         occurrences all number
    503
    899
    Anaemia megaloblastic
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Bandaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Bicytopenia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Bone marrow failure
         subjects affected / exposed
    16 / 833 (1.92%)
    39 / 1685 (2.31%)
         occurrences all number
    31
    76
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Erythropenia
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences all number
    3
    0
    Febrile neutropenia
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences all number
    1
    4
    Granulocytopenia
         subjects affected / exposed
    3 / 833 (0.36%)
    11 / 1685 (0.65%)
         occurrences all number
    19
    21
    Haematotoxicity
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Haemolytic anaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Hypercoagulation
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Increased tendency to bruise
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    4 / 1685 (0.24%)
         occurrences all number
    0
    4
    Leukocytosis
         subjects affected / exposed
    5 / 833 (0.60%)
    11 / 1685 (0.65%)
         occurrences all number
    5
    11
    Leukopenia
         subjects affected / exposed
    40 / 833 (4.80%)
    101 / 1685 (5.99%)
         occurrences all number
    86
    220
    Lymph node pain
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Lymphadenitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Lymphadenopathy
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Lymphopenia
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    5
    1
    Neutropenia
         subjects affected / exposed
    79 / 833 (9.48%)
    202 / 1685 (11.99%)
         occurrences all number
    175
    387
    Neutrophilia
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Pancytopenia
         subjects affected / exposed
    2 / 833 (0.24%)
    4 / 1685 (0.24%)
         occurrences all number
    2
    5
    Platelet disorder
         subjects affected / exposed
    2 / 833 (0.24%)
    4 / 1685 (0.24%)
         occurrences all number
    2
    6
    Platelet production decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    66 / 833 (7.92%)
    156 / 1685 (9.26%)
         occurrences all number
    141
    330
    Thrombocytopenia neonatal
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Thrombocytosis
         subjects affected / exposed
    1 / 833 (0.12%)
    7 / 1685 (0.42%)
         occurrences all number
    2
    8
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Ear pain
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hypoacusis
         subjects affected / exposed
    0 / 833 (0.00%)
    4 / 1685 (0.24%)
         occurrences all number
    0
    4
    Otorrhoea
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Tinnitus
         subjects affected / exposed
    4 / 833 (0.48%)
    3 / 1685 (0.18%)
         occurrences all number
    4
    3
    Vertigo
         subjects affected / exposed
    4 / 833 (0.48%)
    5 / 1685 (0.30%)
         occurrences all number
    5
    5
    Eye disorders
    Asthenopia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Blindness
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Blindness unilateral
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Cataract
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Conjunctival haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Conjunctival pallor
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Diplopia
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Dry eye
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    5
    Eye disorder
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Eye irritation
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Eye pain
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Eyelid margin crusting
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Eyelid oedema
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    4
    Glaucoma
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Keratitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Lacrimation increased
         subjects affected / exposed
    5 / 833 (0.60%)
    7 / 1685 (0.42%)
         occurrences all number
    5
    7
    Ocular hyperaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Photophobia
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Pupils unequal
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Ulcerative keratitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Vision blurred
         subjects affected / exposed
    3 / 833 (0.36%)
    3 / 1685 (0.18%)
         occurrences all number
    3
    3
    Visual impairment
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    3 / 833 (0.36%)
    6 / 1685 (0.36%)
         occurrences all number
    3
    7
    Abdominal distension
         subjects affected / exposed
    8 / 833 (0.96%)
    9 / 1685 (0.53%)
         occurrences all number
    8
    11
    Abdominal pain
         subjects affected / exposed
    18 / 833 (2.16%)
    50 / 1685 (2.97%)
         occurrences all number
    24
    57
    Abdominal pain lower
         subjects affected / exposed
    2 / 833 (0.24%)
    5 / 1685 (0.30%)
         occurrences all number
    2
    5
    Abdominal pain upper
         subjects affected / exposed
    15 / 833 (1.80%)
    17 / 1685 (1.01%)
         occurrences all number
    17
    21
    Abdominal tenderness
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Acute abdomen
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Anal inflammation
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Ascites
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences all number
    2
    2
    Chronic gastritis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Constipation
         subjects affected / exposed
    56 / 833 (6.72%)
    106 / 1685 (6.29%)
         occurrences all number
    71
    121
    Dental caries
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Diarrhoea
         subjects affected / exposed
    46 / 833 (5.52%)
    106 / 1685 (6.29%)
         occurrences all number
    58
    127
    Diverticulum intestinal
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Dry mouth
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Duodenitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Dyspepsia
         subjects affected / exposed
    5 / 833 (0.60%)
    12 / 1685 (0.71%)
         occurrences all number
    5
    13
    Dysphagia
         subjects affected / exposed
    5 / 833 (0.60%)
    16 / 1685 (0.95%)
         occurrences all number
    5
    17
    Enteritis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Epigastric discomfort
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    6
    Faeces hard
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Flatulence
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    4
    Gastric polyps
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Gastric ulcer
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Gastritis
         subjects affected / exposed
    5 / 833 (0.60%)
    11 / 1685 (0.65%)
         occurrences all number
    5
    11
    Gastrointestinal disorder
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    2
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 833 (0.24%)
    6 / 1685 (0.36%)
         occurrences all number
    2
    6
    Gingival swelling
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Glossitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Glossodynia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Haematemesis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Haematochezia
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences all number
    3
    2
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    1
    Haemorrhoids
         subjects affected / exposed
    3 / 833 (0.36%)
    1 / 1685 (0.06%)
         occurrences all number
    3
    1
    Hyperchlorhydria
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Ileus
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Intestinal haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Lip dry
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Lip swelling
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Melaena
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    3 / 833 (0.36%)
    7 / 1685 (0.42%)
         occurrences all number
    3
    7
    Nausea
         subjects affected / exposed
    101 / 833 (12.12%)
    187 / 1685 (11.10%)
         occurrences all number
    163
    270
    Odynophagia
         subjects affected / exposed
    1 / 833 (0.12%)
    5 / 1685 (0.30%)
         occurrences all number
    1
    6
    Oesophageal stenosis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Oesophagitis
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences all number
    2
    2
    Oral disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Oral pain
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    3
    Rectal haemorrhage
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Rectal ulcer
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Regurgitation
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Retching
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    3
    Small intestinal obstruction
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Stomatitis
         subjects affected / exposed
    6 / 833 (0.72%)
    20 / 1685 (1.19%)
         occurrences all number
    7
    22
    Tooth loss
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Toothache
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Vomiting
         subjects affected / exposed
    57 / 833 (6.84%)
    118 / 1685 (7.00%)
         occurrences all number
    73
    164
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Actinic keratosis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Alopecia
         subjects affected / exposed
    70 / 833 (8.40%)
    125 / 1685 (7.42%)
         occurrences all number
    85
    147
    Cold sweat
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Decubitus ulcer
         subjects affected / exposed
    4 / 833 (0.48%)
    4 / 1685 (0.24%)
         occurrences all number
    4
    4
    Dermatitis
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Dermatitis acneiform
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Dermatitis allergic
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Dermatitis bullous
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Drug eruption
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Dry skin
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences all number
    1
    4
    Ecchymosis
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences all number
    1
    4
    Eczema
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    2
    Erythema
         subjects affected / exposed
    5 / 833 (0.60%)
    4 / 1685 (0.24%)
         occurrences all number
    8
    4
    Haemorrhage subcutaneous
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Hand dermatitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hyperhidrosis
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences all number
    1
    4
    Ingrowing nail
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Nail discolouration
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Nail disorder
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Night sweats
         subjects affected / exposed
    3 / 833 (0.36%)
    2 / 1685 (0.12%)
         occurrences all number
    3
    2
    Pain of skin
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Palmar erythema
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Petechiae
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    4
    Photosensitivity reaction
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Pigmentation disorder
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Plantar erythema
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    3 / 833 (0.36%)
    22 / 1685 (1.31%)
         occurrences all number
    3
    25
    Pruritus allergic
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Pruritus generalised
         subjects affected / exposed
    3 / 833 (0.36%)
    1 / 1685 (0.06%)
         occurrences all number
    3
    1
    Purpura
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Rash
         subjects affected / exposed
    14 / 833 (1.68%)
    25 / 1685 (1.48%)
         occurrences all number
    17
    31
    Rash erythematous
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Rash generalised
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Rash pruritic
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Skin discolouration
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Skin disorder
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Skin erosion
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Skin exfoliation
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Skin fissures
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Skin lesion
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Skin mass
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Skin odour abnormal
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Skin ulcer
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Subcutaneous emphysema
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Swelling face
         subjects affected / exposed
    3 / 833 (0.36%)
    2 / 1685 (0.12%)
         occurrences all number
    3
    2
    Urticaria
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Xeroderma
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    3 / 833 (0.36%)
    5 / 1685 (0.30%)
         occurrences all number
    5
    5
    Anuria
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Bladder dilatation
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Calculus bladder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Chronic kidney disease
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Dysuria
         subjects affected / exposed
    1 / 833 (0.12%)
    11 / 1685 (0.65%)
         occurrences all number
    1
    12
    Glycosuria
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Haematuria
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Nephrolithiasis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Nephropathy
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Nocturia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Oliguria
         subjects affected / exposed
    0 / 833 (0.00%)
    4 / 1685 (0.24%)
         occurrences all number
    0
    4
    Pollakiuria
         subjects affected / exposed
    3 / 833 (0.36%)
    2 / 1685 (0.12%)
         occurrences all number
    3
    2
    Proteinuria
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences all number
    2
    2
    Renal failure
         subjects affected / exposed
    5 / 833 (0.60%)
    5 / 1685 (0.30%)
         occurrences all number
    5
    6
    Renal impairment
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences all number
    1
    4
    Renal pain
         subjects affected / exposed
    0 / 833 (0.00%)
    3 / 1685 (0.18%)
         occurrences all number
    0
    3
    Urinary hesitation
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 833 (0.00%)
    4 / 1685 (0.24%)
         occurrences all number
    0
    4
    Urinary retention
         subjects affected / exposed
    3 / 833 (0.36%)
    1 / 1685 (0.06%)
         occurrences all number
    3
    1
    Endocrine disorders
    Goitre
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Hypercalcaemia of malignancy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hyperthyroidism
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Thyroid dysfunction in pregnancy
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Arthralgia
         subjects affected / exposed
    21 / 833 (2.52%)
    32 / 1685 (1.90%)
         occurrences all number
    23
    39
    Back pain
         subjects affected / exposed
    35 / 833 (4.20%)
    65 / 1685 (3.86%)
         occurrences all number
    39
    81
    Bone formation increased
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Bursitis
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    2
    Bone pain
         subjects affected / exposed
    10 / 833 (1.20%)
    30 / 1685 (1.78%)
         occurrences all number
    11
    58
    Coccydynia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Connective tissue disorder
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Exostosis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Fistula
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Flank pain
         subjects affected / exposed
    1 / 833 (0.12%)
    5 / 1685 (0.30%)
         occurrences all number
    1
    5
    Gouty arthritis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hypercreatinaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    3
    Joint range of motion decreased
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Joint swelling
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    1
    Limb discomfort
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Muscle fatigue
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Muscle spasms
         subjects affected / exposed
    5 / 833 (0.60%)
    6 / 1685 (0.36%)
         occurrences all number
    5
    6
    Muscle twitching
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Muscular weakness
         subjects affected / exposed
    9 / 833 (1.08%)
    12 / 1685 (0.71%)
         occurrences all number
    9
    13
    Musculoskeletal chest pain
         subjects affected / exposed
    8 / 833 (0.96%)
    17 / 1685 (1.01%)
         occurrences all number
    9
    24
    Musculoskeletal discomfort
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Musculoskeletal pain
         subjects affected / exposed
    12 / 833 (1.44%)
    25 / 1685 (1.48%)
         occurrences all number
    12
    28
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Myalgia
         subjects affected / exposed
    12 / 833 (1.44%)
    26 / 1685 (1.54%)
         occurrences all number
    19
    34
    Neck pain
         subjects affected / exposed
    4 / 833 (0.48%)
    7 / 1685 (0.42%)
         occurrences all number
    5
    7
    Osteolysis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Osteoporosis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    22 / 833 (2.64%)
    57 / 1685 (3.38%)
         occurrences all number
    32
    69
    Pain in jaw
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Patellofemoral pain syndrome
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Pathological fracture
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Rhabdomyolysis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Spinal pain
         subjects affected / exposed
    1 / 833 (0.12%)
    5 / 1685 (0.30%)
         occurrences all number
    1
    8
    Synovial cyst
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Trismus
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Abdominal wall infection
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Alveolar osteitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Amoebiasis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Anorectal cellulitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Bacterial infection
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Balanoposthitis infective
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Bronchiolitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Bronchitis
         subjects affected / exposed
    7 / 833 (0.84%)
    18 / 1685 (1.07%)
         occurrences all number
    7
    20
    Bronchitis bacterial
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Candida infection
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Catheter site cellulitis
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Cellulitis
         subjects affected / exposed
    2 / 833 (0.24%)
    5 / 1685 (0.30%)
         occurrences all number
    2
    7
    Chikungunya virus infection
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Conjunctivitis
         subjects affected / exposed
    3 / 833 (0.36%)
    4 / 1685 (0.24%)
         occurrences all number
    3
    4
    Cystitis
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Device related infection
         subjects affected / exposed
    0 / 833 (0.00%)
    4 / 1685 (0.24%)
         occurrences all number
    0
    4
    Erysipelas
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Eye infection
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Febrile infection
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Folliculitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Fungal infection
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences all number
    3
    2
    Fungal skin infection
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Furuncle
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Gastroenteritis
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    3
    Gastroenteritis viral
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Gastrointestinal infection
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hepatitis B
         subjects affected / exposed
    2 / 833 (0.24%)
    2 / 1685 (0.12%)
         occurrences all number
    2
    2
    Herpes dermatitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Herpes simplex
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Herpes virus infection
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Herpes zoster
         subjects affected / exposed
    3 / 833 (0.36%)
    7 / 1685 (0.42%)
         occurrences all number
    3
    7
    Infected bite
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Infection
         subjects affected / exposed
    3 / 833 (0.36%)
    4 / 1685 (0.24%)
         occurrences all number
    3
    4
    Influenza
         subjects affected / exposed
    5 / 833 (0.60%)
    8 / 1685 (0.47%)
         occurrences all number
    6
    8
    Kidney infection
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Localised infection
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 833 (0.12%)
    6 / 1685 (0.36%)
         occurrences all number
    1
    7
    Lung infection
         subjects affected / exposed
    6 / 833 (0.72%)
    12 / 1685 (0.71%)
         occurrences all number
    8
    13
    Mastoiditis
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Meningoencephalitis bacterial
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Mucosal infection
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Onychomycosis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Oral candidiasis
         subjects affected / exposed
    2 / 833 (0.24%)
    7 / 1685 (0.42%)
         occurrences all number
    2
    7
    Oral fungal infection
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Oral herpes
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    3
    Oral infection
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Orchitis
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal candidiasis
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Paronychia
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Penile infection
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Pharyngitis
         subjects affected / exposed
    3 / 833 (0.36%)
    3 / 1685 (0.18%)
         occurrences all number
    3
    3
    Pneumonia
         subjects affected / exposed
    13 / 833 (1.56%)
    26 / 1685 (1.54%)
         occurrences all number
    13
    27
    Pneumonia bacterial
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Post procedural infection
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    3
    0
    Rash pustular
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    3 / 833 (0.36%)
    9 / 1685 (0.53%)
         occurrences all number
    3
    10
    Respiratory tract infection viral
         subjects affected / exposed
    5 / 833 (0.60%)
    5 / 1685 (0.30%)
         occurrences all number
    6
    5
    Rhinitis
         subjects affected / exposed
    2 / 833 (0.24%)
    3 / 1685 (0.18%)
         occurrences all number
    2
    3
    Sepsis
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Sinusitis
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences all number
    1
    5
    Skin infection
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Sputum purulent
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Staphylococcal infection
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    2
    Strongyloidiasis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Tinea cruris
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Tonsillitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Tooth infection
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Tracheitis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Tracheobronchitis
         subjects affected / exposed
    3 / 833 (0.36%)
    2 / 1685 (0.12%)
         occurrences all number
    3
    2
    Upper respiratory tract infection
         subjects affected / exposed
    14 / 833 (1.68%)
    33 / 1685 (1.96%)
         occurrences all number
    19
    35
    Urinary tract infection
         subjects affected / exposed
    14 / 833 (1.68%)
    27 / 1685 (1.60%)
         occurrences all number
    15
    32
    Urinary tract infection fungal
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Viral infection
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    3
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    6 / 833 (0.72%)
    8 / 1685 (0.47%)
         occurrences all number
    6
    9
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Wound infection
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Cachexia
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Decreased appetite
         subjects affected / exposed
    63 / 833 (7.56%)
    134 / 1685 (7.95%)
         occurrences all number
    78
    160
    Dehydration
         subjects affected / exposed
    14 / 833 (1.68%)
    37 / 1685 (2.20%)
         occurrences all number
    15
    50
    Diabetes mellitus
         subjects affected / exposed
    4 / 833 (0.48%)
    1 / 1685 (0.06%)
         occurrences all number
    5
    1
    Diabetes mellitus inadequate control
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Dyslipidaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Electrolyte imbalance
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Fluid retention
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Glucose tolerance impaired
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Gout
         subjects affected / exposed
    2 / 833 (0.24%)
    0 / 1685 (0.00%)
         occurrences all number
    2
    0
    Hypercalcaemia
         subjects affected / exposed
    5 / 833 (0.60%)
    4 / 1685 (0.24%)
         occurrences all number
    5
    4
    Hyperchloraemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hypercholesterolaemia
         subjects affected / exposed
    3 / 833 (0.36%)
    1 / 1685 (0.06%)
         occurrences all number
    3
    1
    Hypercreatininaemia
         subjects affected / exposed
    2 / 833 (0.24%)
    4 / 1685 (0.24%)
         occurrences all number
    2
    6
    Hyperglycaemia
         subjects affected / exposed
    14 / 833 (1.68%)
    32 / 1685 (1.90%)
         occurrences all number
    18
    54
    Hyperkalaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    7 / 1685 (0.42%)
         occurrences all number
    1
    8
    Hyperlipidaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hypernatraemia
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Hyperphosphataemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 833 (0.12%)
    3 / 1685 (0.18%)
         occurrences all number
    1
    6
    Hyperuricaemia
         subjects affected / exposed
    2 / 833 (0.24%)
    8 / 1685 (0.47%)
         occurrences all number
    3
    11
    Hypoalbuminaemia
         subjects affected / exposed
    16 / 833 (1.92%)
    47 / 1685 (2.79%)
         occurrences all number
    27
    65
    Hypocalcaemia
         subjects affected / exposed
    11 / 833 (1.32%)
    25 / 1685 (1.48%)
         occurrences all number
    19
    36
    Hypochloraemia
         subjects affected / exposed
    2 / 833 (0.24%)
    1 / 1685 (0.06%)
         occurrences all number
    2
    1
    Hypoglycaemia
         subjects affected / exposed
    4 / 833 (0.48%)
    1 / 1685 (0.06%)
         occurrences all number
    4
    1
    Hypokalaemia
         subjects affected / exposed
    36 / 833 (4.32%)
    53 / 1685 (3.15%)
         occurrences all number
    51
    71
    Hypomagnesaemia
         subjects affected / exposed
    10 / 833 (1.20%)
    9 / 1685 (0.53%)
         occurrences all number
    12
    12
    Hyponatraemia
         subjects affected / exposed
    12 / 833 (1.44%)
    25 / 1685 (1.48%)
         occurrences all number
    19
    33
    Hypophagia
         subjects affected / exposed
    1 / 833 (0.12%)
    2 / 1685 (0.12%)
         occurrences all number
    1
    2
    Hypoproteinaemia
         subjects affected / exposed
    11 / 833 (1.32%)
    9 / 1685 (0.53%)
         occurrences all number
    15
    10
    Hypophosphataemia
         subjects affected / exposed
    3 / 833 (0.36%)
    0 / 1685 (0.00%)
         occurrences all number
    5
    0
    Hypovolaemia
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Iron deficiency
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Malnutrition
         subjects affected / exposed
    1 / 833 (0.12%)
    4 / 1685 (0.24%)
         occurrences all number
    1
    4
    Iron overload
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Marasmus
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Metabolic disorder
         subjects affected / exposed
    1 / 833 (0.12%)
    0 / 1685 (0.00%)
         occurrences all number
    1
    0
    Protein deficiency
         subjects affected / exposed
    0 / 833 (0.00%)
    2 / 1685 (0.12%)
         occurrences all number
    0
    2
    Tetany
         subjects affected / exposed
    0 / 833 (0.00%)
    1 / 1685 (0.06%)
         occurrences all number
    0
    1
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Vitamin D deficiency
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1
    Weight loss poor
         subjects affected / exposed
    1 / 833 (0.12%)
    1 / 1685 (0.06%)
         occurrences all number
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Feb 2009
    The following revisions were made based on regulatory feedback: - Further rationale was provided for the definition of noninferiority (upper limit = 1.15). - The definition of a nonresponder was changed from a subject whose week 10 hemoglobin dropped by > 0.5 g/dL from week 1 or who had a RBC transfusion within 21 days before week 10 to a subject who, after study day 35, received 2 transfusions ≥ 21 days and ≤ 42 days apart. - The end of investigational product administration was changed to the next study visit after the last dose of chemotherapy for consistency with updated product labeling. - The study title was changed to remove "to a hemoglobin ceiling of 12.0 g/dL." - An end of efficacy treatment period definition was added. - The statistical section was revised to clarify the inclusion of fatal events after the 2700th event but before the termination date in the primary analysis. - ANC was replaced with WBC in the Other Analyses section, as ANC is derived and could be missing or inconsistently reported. - Assessment of suspected bone metastases was updated to allow for the use of MRI, CT, or PET/CT in addition to bone scans for the initial assessment.
    22 Mar 2009
    The duration of investigational product administration was clarified (end of treatment within 3 weeks after the last dose of chemotherapy or upon determination of disease progression, whichever occurred first).
    25 May 2010
    The effect of maintenance therapy on subject eligibility and investigational product administration was clarified. Subject eligibility was updated to change stage IIIb with malignant pleural effusion to stage IV in eligibility criteria, consistent with current medical classification of NSCLC. The eligibility criteria were updated to clarify the inclusion of subjects with newly diagnosed stage IV NSCLC and the exclusion of subjects with recurrent disease to reduce possibly heterogeneity in expected OS. Modified RECIST 1.0 was replaced with modified RECIST 1.1 to align with current clinical research practice.
    13 Nov 2012
    Serious adverse event reporting requirements were changed from 1 business day to 24 hours in accordance with updates for the European Medicines Agency guidance. Testing frequencies for total iron-binding capacity, C-reactive protein, and soluble transferrin saturation were corrected.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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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