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    Clinical Trial Results:
    A Phase II/III Randomized Trial of Two Doses of MK-3475 (SCH900475) versus Docetaxel in Previously Treated Subjects with Non-Small Cell Lung Cancer

    Summary
    EudraCT number
    2012-004391-19
    Trial protocol
    CZ   GB   LT   HU   BE   ES   DK   DE   IT   NL   FR   PT   GR  
    Global end of trial date
    30 Sep 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    30 Sep 2021
    First version publication date
    30 Sep 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    3475-010
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01905657
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Merck: KEYNOTE-010, Japic-CTI: 132355
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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
    Interim
    Date of interim/final analysis
    30 Sep 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Sep 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Sep 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study compared two doses of pembrolizumab (MK-3475) versus docetaxel in participants with non-small cell lung cancer (NSCLC) who had experienced disease progression after platinum-containing systemic therapy. Participants were assigned randomly to receive either pembrolizumab 2 mg/kg once every three weeks (Q3W), pembrolizumab 10 mg/kg Q3W or docetaxel 75 mg/m^2 Q3W. The total number of participants randomized depended upon demonstration of sufficient objective responses at an interim analysis.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    09 Aug 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 5
    Country: Number of subjects enrolled
    Australia: 35
    Country: Number of subjects enrolled
    Belgium: 24
    Country: Number of subjects enrolled
    Brazil: 13
    Country: Number of subjects enrolled
    Canada: 19
    Country: Number of subjects enrolled
    Chile: 14
    Country: Number of subjects enrolled
    Czechia: 16
    Country: Number of subjects enrolled
    Denmark: 13
    Country: Number of subjects enrolled
    France: 107
    Country: Number of subjects enrolled
    Germany: 31
    Country: Number of subjects enrolled
    Hungary: 33
    Country: Number of subjects enrolled
    Italy: 25
    Country: Number of subjects enrolled
    Japan: 91
    Country: Number of subjects enrolled
    Korea, Republic of: 84
    Country: Number of subjects enrolled
    Lithuania: 7
    Country: Number of subjects enrolled
    Netherlands: 49
    Country: Number of subjects enrolled
    Portugal: 16
    Country: Number of subjects enrolled
    Russian Federation: 19
    Country: Number of subjects enrolled
    South Africa: 4
    Country: Number of subjects enrolled
    Spain: 114
    Country: Number of subjects enrolled
    Taiwan: 15
    Country: Number of subjects enrolled
    United Kingdom: 56
    Country: Number of subjects enrolled
    United States: 224
    Country: Number of subjects enrolled
    Greece: 20
    Worldwide total number of subjects
    1034
    EEA total number of subjects
    455
    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)
    605
    From 65 to 84 years
    427
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    Participants who had NSCLC and whose tumors were assessed as being programmed cell death ligand 1 (PD-L1) positive were recruited for this study.

    Pre-assignment
    Screening details
    Per protocol response or progression during second and switch over pembrolizumab courses was not counted towards efficacy endpoints and adverse events during the second and switch over courses were not counted towards safety endpoints. Final analyses for all primary and secondary endpoints was done at the protocol-specified cutoff of 30-Sep-2015.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Pembrolizumab 2 mg/kg
    Arm description
    Participants received pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator’s discretion, at 200 mg IV Q3W for up to 1 year.
    Arm type
    Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, KEYTRUDA®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion

    Arm title
    Pembrolizumab 10 mg/kg
    Arm description
    Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator’s discretion, at 200 mg IV Q3W for up to 1 year.
    Arm type
    Experimental

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, KEYTRUDA®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion

    Arm title
    Docetaxel 75 mg/m^2
    Arm description
    Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator’s discretion, at 200 mg IV Q3W for up to 2 years.
    Arm type
    Active comparator

    Investigational medicinal product name
    Pembrolizumab
    Investigational medicinal product code
    Other name
    MK-3475, KEYTRUDA®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    TAXOTERE®
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion

    Number of subjects in period 1
    Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel 75 mg/m^2
    Started
    345
    346
    343
    Treated
    339
    343
    309
    Received second pembrolizumab course
    14 [1]
    7 [2]
    0 [3]
    Switched over to pembrolizumab
    0 [4]
    0 [5]
    8 [6]
    Completed
    142
    159
    143
    Not completed
    203
    187
    200
         Physician decision
    5
    8
    12
         Consent withdrawn by subject
    15
    21
    53
         Screen Failure
    -
    1
    -
         Excluded Medication
    13
    16
    9
         Adverse event, non-fatal
    23
    17
    18
         Death
    40
    43
    47
         Sponsor Decision
    1
    -
    -
         Lost to follow-up
    1
    2
    1
         Clinical Progression
    103
    78
    59
         Protocol deviation
    2
    1
    1
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Treatment with second or crossover course of pembrolizumab was optional.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Treatment with second or crossover course of pembrolizumab was optional.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Treatment with second or crossover course of pembrolizumab was optional.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Treatment with second or crossover course of pembrolizumab was optional.
    [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Treatment with second or crossover course of pembrolizumab was optional.
    [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Treatment with second or crossover course of pembrolizumab was optional.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Pembrolizumab 2 mg/kg
    Reporting group description
    Participants received pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator’s discretion, at 200 mg IV Q3W for up to 1 year.

    Reporting group title
    Pembrolizumab 10 mg/kg
    Reporting group description
    Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator’s discretion, at 200 mg IV Q3W for up to 1 year.

    Reporting group title
    Docetaxel 75 mg/m^2
    Reporting group description
    Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator’s discretion, at 200 mg IV Q3W for up to 2 years.

    Reporting group values
    Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel 75 mg/m^2 Total
    Number of subjects
    345 346 343 1034
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    202 194 209 605
        From 65-84 years
    143 150 134 427
        85 years and over
    0 2 0 2
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    62.1 ( 9.6 ) 62.3 ( 9.7 ) 61.6 ( 9.8 ) -
    Sex: Female, Male
    Units: Participants
        Female
    132 133 134 399
        Male
    213 213 209 635
    PD-L1 Tumor Expression Status
    PD-L1 expression was evaluated by immunohistochemistry (IHC) assay with a newly obtained tumor tissue with biopsy. If PD-L1 expression was observed in ≥1%, but ≤49% of tumor cells, a participant was categorized as weakly PD-L1 positive. If PD-L1 expression was observed in ≥50% of tumor cells, a participant was categorized as strongly PD-L1 positive.
    Units: Subjects
        Weakly PD-L1 Positive
    206 195 191 592
        Strongly PD-L1 Positive
    139 151 152 442

    End points

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    End points reporting groups
    Reporting group title
    Pembrolizumab 2 mg/kg
    Reporting group description
    Participants received pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator’s discretion, at 200 mg IV Q3W for up to 1 year.

    Reporting group title
    Pembrolizumab 10 mg/kg
    Reporting group description
    Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator’s discretion, at 200 mg IV Q3W for up to 1 year.

    Reporting group title
    Docetaxel 75 mg/m^2
    Reporting group description
    Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator’s discretion, at 200 mg IV Q3W for up to 2 years.

    Primary: Overall Survival (OS)

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    End point title
    Overall Survival (OS)
    End point description
    OS was defined as the time from randomization to death due to any cause. OS was analyzed using the Kaplan-Meier method and is reported in months. Per protocol, final analysis for this primary endpoint was done for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 September (Sep) 2015. “9999” indicates upper limit not reached, due to insufficient number of deaths in the study. Analysis population consisted of all randomized participants who had strongly PD-L1 positive and all PD-L1 positive OS data available and usable. Participants were included in the treatment group to which they were randomized.
    End point type
    Primary
    End point timeframe
    Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
    End point values
    Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel 75 mg/m^2
    Number of subjects analysed
    344
    346
    343
    Units: Months
    median (confidence interval 95%)
        Strongly PD-L1 Positive (n=139,151,152)
    14.9 (10.4 to 9999)
    17.3 (11.8 to 9999)
    8.2 (6.4 to 10.7)
        All PD-L1 Positive (n=344, 346, 343)
    10.4 (9.4 to 11.9)
    12.7 (10.0 to 17.3)
    8.5 (7.5 to 9.8)
    Statistical analysis title
    OS Hazard Ratio
    Statistical analysis description
    Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan. Analysis is reported in participants with strongly PD-L1 positive tumors. Numerator=Pembrolizumab 2 mg/kg and Denominator=Docetaxel 75 mg/m^2.
    Comparison groups
    Pembrolizumab 2 mg/kg v Docetaxel 75 mg/m^2
    Number of subjects included in analysis
    687
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.00024
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.38
         upper limit
    0.77
    Statistical analysis title
    OS Hazard Ratio
    Statistical analysis description
    Hazard Ratio based on Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan. Analysis is reported in participants with strongly PD-L1 positive tumors. Numerator=Pembrolizumab 10 mg/kg and Denominator=Docetaxel 75 mg/m^2.
    Comparison groups
    Pembrolizumab 10 mg/kg v Docetaxel 75 mg/m^2
    Number of subjects included in analysis
    689
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.00002
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.36
         upper limit
    0.7
    Statistical analysis title
    OS Hazard Ratio
    Statistical analysis description
    Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan. Analysis is reported in participants with PD-L1 positive tumors. Numerator=Pembrolizumab 2 mg/kg and Denominator=Docetaxel 75 mg/m^2.
    Comparison groups
    Pembrolizumab 2 mg/kg v Docetaxel 75 mg/m^2
    Number of subjects included in analysis
    687
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.00076
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.58
         upper limit
    0.88
    Statistical analysis title
    OS Hazard Ratio
    Statistical analysis description
    Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan. Analysis is reported in participants with PD-L1 positive tumors. Numerator=Pembrolizumab 10 mg/kg and Denominator=Docetaxel 75 mg/m^2.
    Comparison groups
    Pembrolizumab 10 mg/kg v Docetaxel 75 mg/m^2
    Number of subjects included in analysis
    689
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.00001
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.61
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.49
         upper limit
    0.75

    Primary: Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

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    End point title
    Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
    End point description
    PFS was the time from the first day of study treatment to first documented progressive disease (PD) per RECIST 1.1 based on blinded independent central radiologists’ review or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was as either a 20% relative increase in the sum of diameters (SOD) of target lesions taking as reference the smallest sum OR an absolute increase of >5 mm in the SOD OR the appearance of new lesions. PFS was analyzed using Kaplan-Meier method and is reported in months. Per protocol final analysis for this primary endpoint was done for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015. Analysis population consisted of all randomized participants who had strongly PD-L1 positive and all PD-L1 positive PFS data available and usable. Participants were included in the treatment group to which they were randomized.
    End point type
    Primary
    End point timeframe
    Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
    End point values
    Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel 75 mg/m^2
    Number of subjects analysed
    344
    346
    343
    Units: Months
    median (confidence interval 95%)
        Strongly PD-L1 Positive (n=139, 151, 152)
    5.2 (4.0 to 6.5)
    5.2 (4.1 to 8.1)
    4.1 (3.6 to 4.3)
        All PD-L1 Positive (n=344, 346, 343)
    3.9 (3.1 to 4.1)
    4.0 (2.6 to 4.3)
    4.0 (3.1 to 4.2)
    Statistical analysis title
    PFS Hazard Ratio
    Statistical analysis description
    Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan. Analysis is reported in participants with strongly PD-L1 positive tumors. Numerator=Pembrolizumab 2 mg/kg and Denominator=Docetaxel 75 mg/m^2.
    Comparison groups
    Pembrolizumab 2 mg/kg v Docetaxel 75 mg/m^2
    Number of subjects included in analysis
    687
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.00009
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.43
         upper limit
    0.77
    Statistical analysis title
    PFS Hazard Ratio
    Statistical analysis description
    Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan. Analysis is reported in participants with strongly PD-L1 positive tumors. Numerator=Pembrolizumab 10 mg/kg and Denominator=Docetaxel 75 mg/m^2.
    Comparison groups
    Pembrolizumab 10 mg/kg v Docetaxel 75 mg/m^2
    Number of subjects included in analysis
    689
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.00007
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.59
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.45
         upper limit
    0.78
    Statistical analysis title
    PFS Hazard Ratio
    Statistical analysis description
    Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan. Analysis is reported in participants with PD-L1 positive tumors. Numerator=Pembrolizumab 2 mg/kg and Denominator=Docetaxel 75 mg/m^2.
    Comparison groups
    Pembrolizumab 2 mg/kg v Docetaxel 75 mg/m^2
    Number of subjects included in analysis
    687
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.06758
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.73
         upper limit
    1.04
    Statistical analysis title
    PFS Hazard Ratio
    Statistical analysis description
    Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan. Analysis is reported in participants with PD-L1 positive tumors. Numerator=Pembrolizumab 10 mg/kg and Denominator=Docetaxel 75 mg/m^2.
    Comparison groups
    Pembrolizumab 10 mg/kg v Docetaxel 75 mg/m^2
    Number of subjects included in analysis
    689
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.00462
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.79
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.66
         upper limit
    0.94

    Primary: Percentage of Participants Experiencing Adverse Events (AEs)

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    End point title
    Percentage of Participants Experiencing Adverse Events (AEs) [1]
    End point description
    An AE was as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015. Analysis population was the All Participants As Treated (APAT) population consisting of all participants who received ≥1 dose of study drug. Participants were included in the treatment group based on the study treatment they received.
    End point type
    Primary
    End point timeframe
    Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical comparisons between treatment arms of the current study were planned for this endpoint.
    End point values
    Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel 75 mg/m^2
    Number of subjects analysed
    339
    343
    309
    Units: Percentage of Participants
        number (not applicable)
    97.6
    96.2
    96.1
    No statistical analyses for this end point

    Primary: Percentage of Participants Discontinuing Study Drug Due to AEs

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    End point title
    Percentage of Participants Discontinuing Study Drug Due to AEs [2]
    End point description
    An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. Per protocol final analysis for this primary endpoint was done for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015. Analysis population was the APAT population consisting of all participants who got at least one dose of study drug. Participants were included in the treatment group based on the study treatment they received.
    End point type
    Primary
    End point timeframe
    Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical comparisons between treatment arms of the current study were planned for this endpoint.
    End point values
    Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel 75 mg/m^2
    Number of subjects analysed
    339
    343
    309
    Units: Percentage of Participants
        number (not applicable)
    8.3
    7.6
    13.6
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR) by RECIST 1.1

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    End point title
    Overall Response Rate (ORR) by RECIST 1.1
    End point description
    ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) based on blinded independent central radiologists' review using RECIST 1.1. Per protocol, final analysis for this secondary endpoint was done for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015. Analysis population consisted of all randomized participants who had strongly PD-L1 positive and all PD-L1 positive ORR data available and usable. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
    End point values
    Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel 75 mg/m^2
    Number of subjects analysed
    344
    346
    343
    Units: Percentage of Participants
    number (confidence interval 95%)
        Strongly PD-L1 Positive (n=139, 151, 152)
    30.2 (22.7 to 38.6)
    29.1 (22.0 to 37.1)
    7.9 (4.1 to 13.4)
        All PD-L1 Positive (n=344, 346, 343)
    18.0 (14.1 to 22.5)
    18.5 (14.5 to 23.0)
    9.3 (6.5 to 12.9)
    Statistical analysis title
    ORR Difference in Percentage
    Statistical analysis description
    Analysis is reported in participants with strongly PD-L1 positive tumors. Difference in percentage is an adjusted risk difference estimated by stratified Miettinen & Nurminen method.
    Comparison groups
    Pembrolizumab 2 mg/kg v Pembrolizumab 10 mg/kg
    Number of subjects included in analysis
    690
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.66608 [3]
    Method
    Miettinen & Nurminen method
    Parameter type
    Difference in Percentages
    Point estimate
    -2.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.7
         upper limit
    8.2
    Notes
    [3] - P-value indicated for testing a difference in percentage equal to 0 versus a difference in percentage not equal to 0, in accordance with the statistical analysis plan.
    Statistical analysis title
    ORR Difference in Percentage
    Statistical analysis description
    Analysis is reported in participants with strongly PD-L1 positive tumors. Difference in percentage is an adjusted risk difference estimated by stratified Miettinen & Nurminen method.
    Comparison groups
    Pembrolizumab 10 mg/kg v Docetaxel 75 mg/m^2
    Number of subjects included in analysis
    689
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.00001 [4]
    Method
    Miettinen & Nurminen method
    Parameter type
    Difference in Percentages
    Point estimate
    22.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    14
         upper limit
    30.7
    Notes
    [4] - P-value indicated for testing a difference in percentage equal to 0 versus a difference in percentage greater than 0, in accordance with the statistical analysis plan.
    Statistical analysis title
    ORR Difference in Percentage
    Statistical analysis description
    Analysis is reported in participants with PD-L1 positive tumors. Difference in percentage is an adjusted risk difference estimated by stratified Miettinen & Nurminen method.
    Comparison groups
    Pembrolizumab 2 mg/kg v Docetaxel 75 mg/m^2
    Number of subjects included in analysis
    687
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.00045 [5]
    Method
    Miettinen & Nurminen method
    Parameter type
    Difference in Percentages
    Point estimate
    8.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.6
         upper limit
    13.9
    Notes
    [5] - P-value indicated for testing a difference in percentage equal to 0 versus a difference in percentage greater than 0, in accordance with the statistical analysis plan.
    Statistical analysis title
    ORR Difference in Percentage
    Statistical analysis description
    Analysis is reported in participants with PD-L1 positive tumors. Difference in percentage is an adjusted risk difference estimated by stratified Miettinen & Nurminen method.
    Comparison groups
    Pembrolizumab 10 mg/kg v Docetaxel 75 mg/m^2
    Number of subjects included in analysis
    689
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.00024 [6]
    Method
    Miettinen & Nurminen method
    Parameter type
    Difference in Percentages
    Point estimate
    9.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.1
         upper limit
    14.3
    Notes
    [6] - P-value indicated for testing a difference in percentage equal to 0 versus a difference in percentage greater than 0, in accordance with the statistical analysis plan.

    Secondary: Duration of Response (DOR) by RECIST 1.1

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    End point title
    Duration of Response (DOR) by RECIST 1.1
    End point description
    DOR is measured from the time criteria were first met for CR/PR (whichever occurred first) until the first date that death or PD was objectively documented. Non-responders weren’t included in the analysis. DOR was analyzed using the Kaplan-Meier method and is reported in weeks. Per protocol final analysis for this secondary endpoint was done for the first pembrolizumab course and docetaxel treatment arms with a protocol-specified analysis data cutoff date of 30 Sep 2015. “9999” indicates median and upper limit not reached, no progressive disease by the time of last disease assessment. Analysis population consisted of all randomized participants who demonstrated a CR/PR and had strongly PD-L1 positive and all PD-L1 positive DOR data available and usable. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
    End point values
    Pembrolizumab 2 mg/kg Pembrolizumab 10 mg/kg Docetaxel 75 mg/m^2
    Number of subjects analysed
    62
    64
    32
    Units: Weeks
    median (full range (min-max))
        Strongly PD-L1 Positive (n=42, 44, 12)
    9999 (3 to 9999)
    9999 (9 to 9999)
    35 (9 to 9999)
        All PD-L1 Positive (n=62, 64, 32)
    9999 (3 to 9999)
    9999 (9 to 9999)
    27 (6 to 9999)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Safety: Up to ~35 months for pembrolizumab first course and up to additional ~27 months for pembrolizumab second and switch over courses; Deaths: Up to ~83 months for pembrolizumab first, second and switch over courses
    Adverse event reporting additional description
    Safety, deaths were analyzed by treatment (pembrolizumab, docetaxel), course (1st, 2nd, switch over). Deaths: all randomized participants; safety: Participants who got ≥1 dose of study drug. Disease progression (DP) wasn’t an AE unless drug-related; MedDRA terms "Neoplasm progression (NP)", "Malignant NP", "DP" unrelated to study drug are excluded
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Pembrolizumab 2 mg/kg First Course
    Reporting group description
    Participants received pembrolizumab 2 mg/kg IV over 30 minutes Q3W for up to 2 years.

    Reporting group title
    Pembrolizumab 10 mg/kg First Course
    Reporting group description
    Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years.

    Reporting group title
    Docetaxel 75 mg/m^2
    Reporting group description
    Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years.

    Reporting group title
    Pembrolizumab 2 mg/kg First Course to Second Course
    Reporting group description
    Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator’s discretion, at 200 mg IV Q3W for up to 1 year.

    Reporting group title
    Pembrolizumab 10 mg/kg First Course to Second Course
    Reporting group description
    Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator’s discretion, at 200 mg IV Q3W for up to 1 year.

    Reporting group title
    Docetaxel 75 mg/m^2 to Switched Over to Pembrolizumab
    Reporting group description
    Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator’s discretion, at 200 mg IV Q3W for up to 2 years.

    Serious adverse events
    Pembrolizumab 2 mg/kg First Course Pembrolizumab 10 mg/kg First Course Docetaxel 75 mg/m^2 Pembrolizumab 2 mg/kg First Course to Second Course Pembrolizumab 10 mg/kg First Course to Second Course Docetaxel 75 mg/m^2 to Switched Over to Pembrolizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    124 / 339 (36.58%)
    133 / 343 (38.78%)
    107 / 309 (34.63%)
    5 / 14 (35.71%)
    2 / 7 (28.57%)
    1 / 8 (12.50%)
         number of deaths (all causes)
    294
    289
    303
    4
    2
    6
         number of deaths resulting from adverse events
    2
    3
    5
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    0 / 339 (0.00%)
    2 / 343 (0.58%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant pleural effusion
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to central nervous system
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraneoplastic syndrome
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour associated fever
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 339 (0.00%)
    2 / 343 (0.58%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Superior vena cava occlusion
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Superior vena cava syndrome
         subjects affected / exposed
    2 / 339 (0.59%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Axillary pain
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    2 / 339 (0.59%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    3 / 339 (0.88%)
    3 / 343 (0.87%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    3 / 339 (0.88%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    2 / 339 (0.59%)
    1 / 343 (0.29%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 339 (0.88%)
    4 / 343 (1.17%)
    4 / 309 (1.29%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 4
    1 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Aspiration
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchial haemorrhage
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    6 / 339 (1.77%)
    1 / 343 (0.29%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    6 / 339 (1.77%)
    2 / 343 (0.58%)
    6 / 309 (1.94%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    1 / 2
    3 / 7
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    3 / 339 (0.88%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Painful respiration
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    3 / 339 (0.88%)
    4 / 343 (1.17%)
    3 / 309 (0.97%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 5
    2 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 339 (0.29%)
    2 / 343 (0.58%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    14 / 339 (4.13%)
    10 / 343 (2.92%)
    2 / 309 (0.65%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    13 / 15
    9 / 10
    2 / 2
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    2 / 2
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    3 / 309 (0.97%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    8 / 339 (2.36%)
    8 / 343 (2.33%)
    5 / 309 (1.62%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 8
    0 / 5
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 339 (0.29%)
    2 / 343 (0.58%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary vascular disorder
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    2 / 339 (0.59%)
    1 / 343 (0.29%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    3 / 339 (0.88%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia, obstructive
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiation pneumonitis
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    2 / 339 (0.59%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Pyloric stenosis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tracheo-oesophageal fistula
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    3 / 339 (0.88%)
    1 / 343 (0.29%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 339 (0.00%)
    2 / 343 (0.58%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    3 / 339 (0.88%)
    2 / 343 (0.58%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Restrictive cardiomyopathy
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 339 (0.29%)
    2 / 343 (0.58%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelitis transverse
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurological decompensation
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 339 (0.00%)
    2 / 343 (0.58%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic leukoencephalopathy
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 339 (0.88%)
    4 / 343 (1.17%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eosinophilia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    11 / 309 (3.56%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    10 / 11
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymph node pain
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Microcytic anaemia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    5 / 309 (1.62%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    4 / 5
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Normocytic anaemia
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 339 (0.59%)
    1 / 343 (0.29%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autoimmune pancreatitis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    3 / 339 (0.88%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 339 (0.29%)
    2 / 343 (0.58%)
    3 / 309 (0.97%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 2
    3 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 339 (0.00%)
    2 / 343 (0.58%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    2 / 339 (0.59%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intra-abdominal haemorrhage
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 339 (0.59%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal hypomotility
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal obstruction
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal stenosis
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    2 / 339 (0.59%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Autoimmune hepatitis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    2 / 339 (0.59%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Drug eruption
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 339 (0.59%)
    2 / 343 (0.58%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder hypertrophy
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary bladder polyp
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    2 / 339 (0.59%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 339 (0.00%)
    2 / 343 (0.58%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adrenal suppression
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    0 / 339 (0.00%)
    2 / 343 (0.58%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypophysitis
         subjects affected / exposed
    0 / 339 (0.00%)
    2 / 343 (0.58%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypopituitarism
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypothyroidism
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    3 / 339 (0.88%)
    2 / 343 (0.58%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle fatigue
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle haemorrhage
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle necrosis
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    2 / 339 (0.59%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myopathy
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoporosis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoporotic fracture
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendonitis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tenosynovitis
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    3 / 309 (0.97%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    External ear cellulitis
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine infection
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal infection
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Phlebitis infective
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural infection
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    20 / 339 (5.90%)
    21 / 343 (6.12%)
    19 / 309 (6.15%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    3 / 22
    2 / 22
    6 / 22
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 4
    0 / 4
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 339 (0.29%)
    2 / 343 (0.58%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia haemophilus
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyopneumothorax
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    4 / 339 (1.18%)
    3 / 343 (0.87%)
    3 / 309 (0.97%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    1 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    3 / 309 (0.97%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound sepsis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infective spondylitis
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis externa
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    3 / 309 (0.97%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 339 (0.29%)
    2 / 343 (0.58%)
    4 / 309 (1.29%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    3 / 4
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 339 (0.29%)
    5 / 343 (1.46%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 339 (0.29%)
    2 / 343 (0.58%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Pembrolizumab 2 mg/kg First Course Pembrolizumab 10 mg/kg First Course Docetaxel 75 mg/m^2 Pembrolizumab 2 mg/kg First Course to Second Course Pembrolizumab 10 mg/kg First Course to Second Course Docetaxel 75 mg/m^2 to Switched Over to Pembrolizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    312 / 339 (92.04%)
    301 / 343 (87.76%)
    279 / 309 (90.29%)
    9 / 14 (64.29%)
    5 / 7 (71.43%)
    7 / 8 (87.50%)
    Vascular disorders
    Embolism
         subjects affected / exposed
    2 / 339 (0.59%)
    1 / 343 (0.29%)
    1 / 309 (0.32%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    2
    1
    1
    1
    0
    0
    Hypertension
         subjects affected / exposed
    15 / 339 (4.42%)
    12 / 343 (3.50%)
    6 / 309 (1.94%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    16
    12
    7
    0
    0
    3
    Orthostatic hypotension
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    2 / 309 (0.65%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences all number
    1
    1
    3
    0
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    44 / 339 (12.98%)
    45 / 343 (13.12%)
    51 / 309 (16.50%)
    0 / 14 (0.00%)
    2 / 7 (28.57%)
    0 / 8 (0.00%)
         occurrences all number
    60
    59
    72
    0
    2
    0
    Chest pain
         subjects affected / exposed
    25 / 339 (7.37%)
    32 / 343 (9.33%)
    22 / 309 (7.12%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences all number
    26
    40
    23
    0
    1
    0
    Fatigue
         subjects affected / exposed
    102 / 339 (30.09%)
    88 / 343 (25.66%)
    106 / 309 (34.30%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
    1 / 8 (12.50%)
         occurrences all number
    122
    107
    131
    0
    1
    1
    Oedema peripheral
         subjects affected / exposed
    30 / 339 (8.85%)
    28 / 343 (8.16%)
    34 / 309 (11.00%)
    1 / 14 (7.14%)
    1 / 7 (14.29%)
    1 / 8 (12.50%)
         occurrences all number
    35
    30
    37
    1
    1
    1
    Pyrexia
         subjects affected / exposed
    51 / 339 (15.04%)
    40 / 343 (11.66%)
    42 / 309 (13.59%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    68
    64
    56
    2
    0
    0
    Gait disturbance
         subjects affected / exposed
    1 / 339 (0.29%)
    1 / 343 (0.29%)
    4 / 309 (1.29%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences all number
    1
    1
    4
    0
    1
    0
    Influenza like illness
         subjects affected / exposed
    9 / 339 (2.65%)
    12 / 343 (3.50%)
    3 / 309 (0.97%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    15
    16
    6
    1
    0
    1
    Infusion site extravasation
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    4 / 309 (1.29%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    1
    4
    0
    0
    1
    Injection site haemorrhage
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Oedema
         subjects affected / exposed
    7 / 339 (2.06%)
    3 / 343 (0.87%)
    6 / 309 (1.94%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    9
    3
    6
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    82 / 339 (24.19%)
    75 / 343 (21.87%)
    43 / 309 (13.92%)
    2 / 14 (14.29%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    104
    94
    47
    2
    0
    1
    Dyspnoea
         subjects affected / exposed
    81 / 339 (23.89%)
    79 / 343 (23.03%)
    65 / 309 (21.04%)
    2 / 14 (14.29%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences all number
    92
    95
    71
    2
    1
    0
    Haemoptysis
         subjects affected / exposed
    26 / 339 (7.67%)
    26 / 343 (7.58%)
    20 / 309 (6.47%)
    1 / 14 (7.14%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences all number
    37
    33
    29
    1
    1
    0
    Productive cough
         subjects affected / exposed
    21 / 339 (6.19%)
    30 / 343 (8.75%)
    10 / 309 (3.24%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences all number
    30
    32
    12
    0
    1
    0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    3 / 339 (0.88%)
    8 / 343 (2.33%)
    1 / 309 (0.32%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    4
    8
    1
    0
    0
    1
    Dysphonia
         subjects affected / exposed
    13 / 339 (3.83%)
    8 / 343 (2.33%)
    9 / 309 (2.91%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    14
    9
    9
    1
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    9 / 339 (2.65%)
    12 / 343 (3.50%)
    7 / 309 (2.27%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    11
    12
    7
    0
    0
    1
    Pneumonitis
         subjects affected / exposed
    8 / 339 (2.36%)
    7 / 343 (2.04%)
    1 / 309 (0.32%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    9
    8
    1
    1
    0
    0
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 339 (0.00%)
    0 / 343 (0.00%)
    1 / 309 (0.32%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Sputum discoloured
         subjects affected / exposed
    2 / 339 (0.59%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences all number
    2
    1
    0
    0
    2
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    18 / 339 (5.31%)
    16 / 343 (4.66%)
    9 / 309 (2.91%)
    0 / 14 (0.00%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences all number
    19
    16
    9
    0
    1
    0
    Insomnia
         subjects affected / exposed
    27 / 339 (7.96%)
    22 / 343 (6.41%)
    22 / 309 (7.12%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    29
    22
    24
    0
    0
    1
    Depressed mood
         subjects affected / exposed
    0 / 339 (0.00%)
    3 / 343 (0.87%)
    1 / 309 (0.32%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    4
    1
    1
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    26 / 339 (7.67%)
    20 / 343 (5.83%)
    5 / 309 (1.62%)
    1 / 14 (7.14%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences all number
    35
    22
    6
    2
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    20 / 339 (5.90%)
    21 / 343 (6.12%)
    4 / 309 (1.29%)
    1 / 14 (7.14%)
    1 / 7 (14.29%)
    0 / 8 (0.00%)
         occurrences all number
    29
    24
    4
    2
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    12 / 339 (3.54%)
    19 / 343 (5.54%)
    5 / 309 (1.62%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    16
    19
    5
    2
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    19 / 339 (5.60%)
    17 / 343 (4.96%)
    4 / 309 (1.29%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    26
    20
    4
    1
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    3 / 339 (0.88%)
    3 / 343 (0.87%)
    25 / 309 (8.09%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    4
    4
    45
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    32 / 339 (9.44%)
    33 / 343 (9.62%)
    11 / 309 (3.56%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    37
    34
    13
    0
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 339 (0.00%)
    3 / 343 (0.87%)
    17 / 309 (5.50%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    6
    29
    0
    0
    0
    Amylase increased
         subjects affected / exposed
    0 / 339 (0.00%)
    1 / 343 (0.29%)
    0 / 309 (0.00%)
    0 / 14 (0.00%)
    0 / 7 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    2
    0
    0
    0
    1
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    5 / 339 (1.47%)
    4 / 343 (1.17%)
    0 / 309 (0.00%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    5
    6
    0
    1
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    15 / 339 (4.42%)
    5 / 343 (1.46%)
    3 / 309 (0.97%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    20
    5
    4
    1
    0
    0
    Serum ferritin decreased
         subjects affected / exposed
    1 / 339 (0.29%)
    0 / 343 (0.00%)
    0 / 309 (0.00%)
    1 / 14 (7.14%)
    0 / 7 (0.00%)
    0 / 8 (0.