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    Clinical Trial Results:
    A Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination with Docetaxel, Compared with Placebo in Combination with Docetaxel, in Patients receiving second line treatment for Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV) (SELECT-2)

    Summary
    EudraCT number
    		 2012-003622-25
    Trial protocol
    		 HU   DE   NL   BG  
    Global end of trial date
    31 Oct 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Aug 2023
    First version publication date
    19 Aug 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D1532C00064
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    132 Hills Rd, Cambridge, United Kingdom, CB2 1PG
    Public contact
    Dr Gabriella Mariani, Astrazeneca, +44 0207 6048000, ClinicalTrialTransparency@astrazeneca.com
    Scientific contact
    Dr Gabriella Mariani, Astrazeneca, +44 0207 6048000, ClinicalTrialTransparency@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 Jan 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Jan 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Oct 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to assess the efficacy in terms of Progression Free Survival (PFS) for each comparison of selumetinib in combination with docetaxel, compared to placebo in combination with docetaxel.
    Protection of trial subjects
    A treatment discontinuation visit was conducted as soon as possible after the patient received the last dose of the last study drug (selumetinib/placebo or docetaxel). Collection of AEs/serious adverse events (SAEs) continued until 30 days after the last dose of study treatment for patient’s withdrawal from study. Thirty days after permanent discontinuation of the last study treatment (selumetinib/placebo or docetaxel), a treatment discontinuation follow up contact was performed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Dec 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 23
    Country: Number of subjects enrolled
    Germany: 42
    Country: Number of subjects enrolled
    Hungary: 50
    Country: Number of subjects enrolled
    Brazil: 39
    Country: Number of subjects enrolled
    United States: 19
    Country: Number of subjects enrolled
    Netherlands: 14
    Country: Number of subjects enrolled
    Bulgaria: 22
    Country: Number of subjects enrolled
    Poland: 3
    Worldwide total number of subjects
    212
    EEA total number of subjects
    154
    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)
    132
    From 65 to 84 years
    80
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Initially the study protocol allowed patients with KRASm (KRAS mutation positive), KRAS NMD (No mutation detected) and KRAS mutation status unknown. Recruitment was put on hold after the 77th patient was randomised in September 2013, to allow a protocol amendment to include only patients with centrally confirmed KRAS NMD NSCLC to be enrolled.

    Pre-assignment
    Screening details
    		 Of the 337 enrolled patients, 212 patients were randomised into the study. All 212 patients who were randomised into the study were included in the Full Analysis Set (FAS). A total of 211 patients received at least 1 dose of treatment and were included in the safety analysis set. Patients received selumetinib (AZD6244; ARRY-142886) or Placebo.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo + Docetaxel 75 mg/m2
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo + Docetaxel 75 mg/m2
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo in combination with docetaxel intravenous [iv] 75 mg/m2 (hereafter referred to as Doc 75 mg/m2 alone)

    Arm title
    		 Selumetinib 75 mg BD + Docetaxel 60 mg/m2
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Selumetinib 75 mg BD + Docetaxel 60 mg/m2
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Selumetinib 75 mg twice daily in combination with docetaxel intravenous [iv] 60 mg/m2 (hereafter referred to as Sel 75 mg + Doc 60 mg/m2)

    Arm title
    		 Selumetinib 75 mg BD + Docetaxel 75 mg/m2
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Selumetinib 75 mg BD + Docetaxel 75 mg/m2
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Selumetinib 75 mg twice daily in combination with docetaxel intravenous [iv] 75 mg/m2 (hereafter referred to as Sel 75 mg + Doc 75 mg/m2)

    Number of subjects in period 1
    		Placebo + Docetaxel 75 mg/m2 Selumetinib 75 mg BD + Docetaxel 60 mg/m2 Selumetinib 75 mg BD + Docetaxel 75 mg/m2
    Started
    43
    85
    84
    Received Treatment
    43
    84
    84
    Did not receive Treatment
    0
    1
    0
    Completed
    0
    0
    0
    Not completed
    43
    85
    84
         Ongoing Selumetinib/Pbo at data cut-off
    6
    7
    9
         Discontinued Selumetinib/Placebo
    37
    77
    75
         Did not receive treatment
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo + Docetaxel 75 mg/m2
    Reporting group description
    		 -

    Reporting group title
    Selumetinib 75 mg BD + Docetaxel 60 mg/m2
    Reporting group description
    		 -

    Reporting group title
    Selumetinib 75 mg BD + Docetaxel 75 mg/m2
    Reporting group description
    		 -

    Reporting group values
    		 Placebo + Docetaxel 75 mg/m2 Selumetinib 75 mg BD + Docetaxel 60 mg/m2 Selumetinib 75 mg BD + Docetaxel 75 mg/m2 Total
    Number of subjects
    		 43 85 84 212
    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)
    		 26 51 55 132
        From 65-84 years
    		 17 34 29 80
        85 years and over
    		 0 0 0 0
    Age Continuous |
    Units: Years
        arithmetic mean (standard deviation)
    		 63.6 ( 7.75 ) 62.4 ( 8.53 ) 60.4 ( 9.35 ) -
    Gender, Male/Female
    Units: Participants
        Female
    		 16 19 26 61
        Male
    		 27 66 58 151
    Study Specific Characteristic
    KRAS Mutation Status at Baseline
    Units: Subjects
        KRAS no mutation detected (NMD)
    		 30 62 54 146
        KRAS mutation positive
    		 10 15 19 44
        KRAS mutation unknown
    		 3 8 11 22

    End points

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    End points reporting groups
    Reporting group title
    Placebo + Docetaxel 75 mg/m2
    Reporting group description
    		 -

    Reporting group title
    Selumetinib 75 mg BD + Docetaxel 60 mg/m2
    Reporting group description
    		 -

    Reporting group title
    Selumetinib 75 mg BD + Docetaxel 75 mg/m2
    Reporting group description
    		 -

    Primary: Progression Free Survival (PFS)

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    End point title
    		 Progression Free Survival (PFS)
    End point description
    Time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression)
    End point type
    Primary
    End point timeframe
    Baseline and then every 6 weeks after randomization until objective disease progression
    End point values
    		 Placebo + Docetaxel 75 mg/m2 Selumetinib 75 mg BD + Docetaxel 60 mg/m2 Selumetinib 75 mg BD + Docetaxel 75 mg/m2
    Number of subjects analysed
    43
    85
    84
    Units: Months
        median (full range (min-max))
    4.3 (0 to 15)
    3.0 (0 to 33)
    4.2 (0 to 28.5)
    Statistical analysis title
    		 PFS
    Statistical analysis description
    Median time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression)
    Comparison groups
    Placebo + Docetaxel 75 mg/m2 v Selumetinib 75 mg BD + Docetaxel 60 mg/m2
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    P-value
    		 = 0.584
    Method
    		 Cox Proportional Hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.12
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.61
    Notes
    [1] - A hazard ratio <1 favours selumetinib in combination with docetaxel
    Statistical analysis title
    		 PFS
    Statistical analysis description
    Median time from randomisation until the date of objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) or death (by any cause in the absence of progression)
    Comparison groups
    Placebo + Docetaxel 75 mg/m2 v Selumetinib 75 mg BD + Docetaxel 75 mg/m2
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    P-value
    		 = 0.69
    Method
    		 Cox Proportional Hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.92
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 1.31
    Notes
    [2] - A hazard ratio <1 favours selumetinib in combination with docetaxel

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    the time from randomisation until death due to any cause. Any subject not known to have died at the time of analysis will be censored based on the last recorded date on which the subject was known to be alive
    End point type
    Secondary
    End point timeframe
    Following progression, survival status was collected every 8 weeks until death, withdrawal of consent, or end of study, whichever occurred first
    End point values
    		 Placebo + Docetaxel 75 mg/m2 Selumetinib 75 mg BD + Docetaxel 60 mg/m2 Selumetinib 75 mg BD + Docetaxel 75 mg/m2
    Number of subjects analysed
    43
    85
    84
    Units: Months
        median (full range (min-max))
    11.5 (0 to 33.5)
    5.7 (0 to 34)
    7.7 (0 to 32)
    Statistical analysis title
    		 OS
    Statistical analysis description
    the time from randomisation until death due to any cause. Any subject not known to have died at the time of analysis will be censored based on the last recorded date on which the subject was known to be alive
    Comparison groups
    Placebo + Docetaxel 75 mg/m2 v Selumetinib 75 mg BD + Docetaxel 75 mg/m2
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 [3]
    P-value
    		 = 0.485
    Method
    		 Cox Proportional Hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.18
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.78
    Notes
    [3] - A hazard ratio <1 favours selumetinib in combination with docetaxel
    Statistical analysis title
    		 OS
    Statistical analysis description
    the time from randomisation until death due to any cause. Any subject not known to have died at the time of analysis will be censored based on the last recorded date on which the subject was known to be alive
    Comparison groups
    Placebo + Docetaxel 75 mg/m2 v Selumetinib 75 mg BD + Docetaxel 60 mg/m2
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    P-value
    		 = 0.126
    Method
    		 Cox Proportional Hazards
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.43
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 2.13
    Notes
    [4] - A hazard ratio <1 favours selumetinib in combination with docetaxel

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs were collected from informed consent, throughout the treatment period until 30 days after discontinuation of the study treatment
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Placebo + Docetaxel 75 mg/m2
    Reporting group description
    		 -

    Reporting group title
    Selumetinib 75 mg BD + Docetaxel 75 mg/m2
    Reporting group description
    		 -

    Reporting group title
    Selumetinib 75 mg BD + Docetaxel 60 mg/m2
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo + Docetaxel 75 mg/m2 Selumetinib 75 mg BD + Docetaxel 75 mg/m2 Selumetinib 75 mg BD + Docetaxel 60 mg/m2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 43 (37.21%)
    38 / 84 (45.24%)
    40 / 84 (47.62%)
         number of deaths (all causes)
    26
    57
    64
         number of deaths resulting from adverse events
    1
    7
    5
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cholesteatoma
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic thrombosis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Performance status decreased
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Pneumothorax spontaneous
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 84 (3.57%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 43 (2.33%)
    4 / 84 (4.76%)
    4 / 84 (4.76%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatine phosphokinase MB increased
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood urea increased
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glomerular filtration rate decreased
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Chemical peritonitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Fall
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic right ventricular failure
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Dizziness
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    3 / 43 (6.98%)
    4 / 84 (4.76%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glossitis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Rectal haemorrhage
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholestasis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Swelling face
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dermatitis bullous
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pneumonia pseudomonal
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 43 (2.33%)
    4 / 84 (4.76%)
    10 / 84 (11.90%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
    3 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 43 (2.33%)
    4 / 84 (4.76%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo + Docetaxel 75 mg/m2 Selumetinib 75 mg BD + Docetaxel 75 mg/m2 Selumetinib 75 mg BD + Docetaxel 60 mg/m2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    39 / 43 (90.70%)
    83 / 84 (98.81%)
    81 / 84 (96.43%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Oncologic complication
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Tumour pain
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    4 / 84 (4.76%)
         occurrences all number
    0
    2
    4
    Vascular disorders
    Thrombophlebitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Circulatory collapse
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Embolism
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Flushing
         subjects affected / exposed
    3 / 43 (6.98%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    3
    0
    0
    Hot flush
         subjects affected / exposed
    2 / 43 (4.65%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    2
    0
    0
    Hypertension
         subjects affected / exposed
    3 / 43 (6.98%)
    10 / 84 (11.90%)
    2 / 84 (2.38%)
         occurrences all number
    4
    11
    2
    Hypotension
         subjects affected / exposed
    2 / 43 (4.65%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences all number
    2
    2
    1
    Lymphoedema
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences all number
    0
    2
    1
    Orthostatic hypotension
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Peripheral coldness
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Phlebitis
         subjects affected / exposed
    2 / 43 (4.65%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    2
    0
    1
    Superior vena cava syndrome
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    1
    0
    1
    Chest discomfort
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Extravasation
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Face oedema
         subjects affected / exposed
    0 / 43 (0.00%)
    4 / 84 (4.76%)
    4 / 84 (4.76%)
         occurrences all number
    0
    4
    4
    Fatigue
         subjects affected / exposed
    13 / 43 (30.23%)
    26 / 84 (30.95%)
    17 / 84 (20.24%)
         occurrences all number
    17
    32
    21
    General physical health deterioration
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences all number
    0
    2
    1
    Generalised oedema
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 84 (3.57%)
    0 / 84 (0.00%)
         occurrences all number
    0
    3
    0
    Hyperthermia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 84 (3.57%)
    2 / 84 (2.38%)
         occurrences all number
    1
    3
    2
    Malaise
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Mucosal inflammation
         subjects affected / exposed
    1 / 43 (2.33%)
    7 / 84 (8.33%)
    1 / 84 (1.19%)
         occurrences all number
    1
    8
    1
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    1
    0
    Oedema
         subjects affected / exposed
    0 / 43 (0.00%)
    4 / 84 (4.76%)
    0 / 84 (0.00%)
         occurrences all number
    0
    4
    0
    Asthenia
         subjects affected / exposed
    2 / 43 (4.65%)
    13 / 84 (15.48%)
    12 / 84 (14.29%)
         occurrences all number
    2
    14
    12
    Catheter site related reaction
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Chills
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    1
    2
    0
    Oedema peripheral
         subjects affected / exposed
    8 / 43 (18.60%)
    28 / 84 (33.33%)
    16 / 84 (19.05%)
         occurrences all number
    10
    38
    22
    Performance status decreased
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    1
    0
    Pyrexia
         subjects affected / exposed
    3 / 43 (6.98%)
    11 / 84 (13.10%)
    11 / 84 (13.10%)
         occurrences all number
    5
    20
    15
    Pain
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    2 / 43 (4.65%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    2
    0
    0
    Reproductive system and breast disorders
    Balanoposthitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Pelvic pain
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Vulvovaginal pruritus
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Emphysema
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Aspiration
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Atelectasis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Bronchospasm
         subjects affected / exposed
    2 / 43 (4.65%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    2
    2
    0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    3 / 84 (3.57%)
         occurrences all number
    1
    0
    3
    Cough
         subjects affected / exposed
    8 / 43 (18.60%)
    10 / 84 (11.90%)
    7 / 84 (8.33%)
         occurrences all number
    8
    10
    7
    Dysphonia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    2 / 84 (2.38%)
         occurrences all number
    0
    1
    2
    Dyspnoea
         subjects affected / exposed
    4 / 43 (9.30%)
    14 / 84 (16.67%)
    12 / 84 (14.29%)
         occurrences all number
    4
    15
    12
    Dyspnoea exertional
         subjects affected / exposed
    2 / 43 (4.65%)
    4 / 84 (4.76%)
    3 / 84 (3.57%)
         occurrences all number
    2
    4
    3
    Epistaxis
         subjects affected / exposed
    2 / 43 (4.65%)
    8 / 84 (9.52%)
    6 / 84 (7.14%)
         occurrences all number
    3
    9
    6
    Pulmonary oedema
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Hypoxia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Lung disorder
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Lung infiltration
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Nasal discomfort
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Nasal dryness
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Nasal inflammation
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Nasal polyps
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 43 (0.00%)
    5 / 84 (5.95%)
    3 / 84 (3.57%)
         occurrences all number
    0
    5
    3
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Pleural effusion
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 84 (3.57%)
    3 / 84 (3.57%)
         occurrences all number
    1
    3
    3
    Pleuritic pain
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Pneumonitis
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    2
    0
    Pneumothorax
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Productive cough
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Pulmonary embolism
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Pulmonary hypertension
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Haemoptysis
         subjects affected / exposed
    2 / 43 (4.65%)
    7 / 84 (8.33%)
    1 / 84 (1.19%)
         occurrences all number
    2
    8
    1
    Rales
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Sinus disorder
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    2
    0
    0
    Sputum discoloured
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Wheezing
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    3 / 84 (3.57%)
         occurrences all number
    0
    1
    3
    Delirium
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Depression
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Disorientation
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Insomnia
         subjects affected / exposed
    2 / 43 (4.65%)
    3 / 84 (3.57%)
    4 / 84 (4.76%)
         occurrences all number
    2
    3
    5
    Sleep disorder
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    3
    2
    0
    Investigations
    International normalised ratio increased
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    4 / 84 (4.76%)
         occurrences all number
    0
    2
    4
    Blood calcium decreased
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Blood creatine phosphokinase MB increased
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 43 (0.00%)
    5 / 84 (5.95%)
    3 / 84 (3.57%)
         occurrences all number
    0
    11
    11
    Blood creatinine increased
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    1
    1
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Blood magnesium decreased
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    2 / 84 (2.38%)
         occurrences all number
    0
    0
    2
    Blood pressure systolic increased
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Blood sodium decreased
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Blood triglycerides increased
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Breath sounds abnormal
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    2
    0
    Ejection fraction decreased
         subjects affected / exposed
    2 / 43 (4.65%)
    2 / 84 (2.38%)
    4 / 84 (4.76%)
         occurrences all number
    2
    2
    4
    Haemoglobin decreased
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Hepatic enzyme abnormal
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    4 / 84 (4.76%)
         occurrences all number
    0
    0
    4
    Prothrombin time prolonged
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Platelet count decreased
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Weight increased
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    White blood cell count decreased
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Weight decreased
         subjects affected / exposed
    4 / 43 (9.30%)
    6 / 84 (7.14%)
    3 / 84 (3.57%)
         occurrences all number
    4
    6
    3
    Intraocular pressure increased
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Bone contusion
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Contusion
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 84 (3.57%)
    0 / 84 (0.00%)
         occurrences all number
    0
    4
    0
    Fall
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    2 / 84 (2.38%)
         occurrences all number
    1
    1
    2
    Head injury
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Laceration
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Overdose
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Rib fracture
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Seroma
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Skin abrasion
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Spinal compression fracture
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Sunburn
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    1
    0
    Tendon rupture
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Wound
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Cardiac disorders
    Cardiac failure congestive
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Atrial fibrillation
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 84 (3.57%)
    3 / 84 (3.57%)
         occurrences all number
    1
    4
    3
    Atrial flutter
         subjects affected / exposed
    2 / 43 (4.65%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    2
    0
    0
    Atrial tachycardia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Bundle branch block left
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Cardiac failure
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Arrhythmia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    1
    0
    Sinus tachycardia
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences all number
    1
    2
    1
    Mitral valve incompetence
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Nodal rhythm
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Palpitations
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Pericarditis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Right ventricular failure
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Tachycardia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    2 / 84 (2.38%)
         occurrences all number
    0
    1
    2
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Depressed level of consciousness
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Dizziness
         subjects affected / exposed
    7 / 43 (16.28%)
    5 / 84 (5.95%)
    5 / 84 (5.95%)
         occurrences all number
    7
    5
    5
    Dizziness postural
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Dysaesthesia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Dysarthria
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Dysgeusia
         subjects affected / exposed
    3 / 43 (6.98%)
    8 / 84 (9.52%)
    6 / 84 (7.14%)
         occurrences all number
    3
    8
    6
    Head discomfort
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    1
    0
    Headache
         subjects affected / exposed
    5 / 43 (11.63%)
    3 / 84 (3.57%)
    6 / 84 (7.14%)
         occurrences all number
    5
    3
    6
    Hemiparesis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Hypoaesthesia
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    1
    0
    1
    Hypokinesia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Hypotonia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Ageusia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Amnesia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Lethargy
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 43 (2.33%)
    4 / 84 (4.76%)
    1 / 84 (1.19%)
         occurrences all number
    1
    4
    1
    Paraesthesia
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 84 (3.57%)
    3 / 84 (3.57%)
         occurrences all number
    0
    3
    4
    Peripheral motor neuropathy
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    1
    0
    1
    Peripheral sensory neuropathy
         subjects affected / exposed
    2 / 43 (4.65%)
    4 / 84 (4.76%)
    4 / 84 (4.76%)
         occurrences all number
    2
    4
    4
    Polyneuropathy
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 84 (3.57%)
    4 / 84 (4.76%)
         occurrences all number
    1
    4
    4
    Somnolence
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    2 / 84 (2.38%)
         occurrences all number
    0
    0
    2
    Tremor
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Vocal cord paralysis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Memory impairment
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 43 (9.30%)
    18 / 84 (21.43%)
    20 / 84 (23.81%)
         occurrences all number
    4
    21
    22
    Leukocytosis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    2 / 84 (2.38%)
         occurrences all number
    1
    0
    2
    Febrile neutropenia
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 84 (3.57%)
    1 / 84 (1.19%)
         occurrences all number
    0
    4
    1
    Eosinophilia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Leukopenia
         subjects affected / exposed
    2 / 43 (4.65%)
    3 / 84 (3.57%)
    2 / 84 (2.38%)
         occurrences all number
    3
    3
    2
    Lymphadenopathy
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Neutropenia
         subjects affected / exposed
    10 / 43 (23.26%)
    17 / 84 (20.24%)
    9 / 84 (10.71%)
         occurrences all number
    12
    19
    26
    Neutrophilia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 84 (2.38%)
    2 / 84 (2.38%)
         occurrences all number
    1
    3
    2
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Hearing impaired
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Middle ear inflammation
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Otorrhoea
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Tinnitus
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Vertigo
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    2 / 84 (2.38%)
         occurrences all number
    1
    1
    2
    Eye disorders
    Blepharitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Chorioretinal disorder
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Dry eye
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 84 (3.57%)
    1 / 84 (1.19%)
         occurrences all number
    1
    3
    1
    Eye discharge
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Eye disorder
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Eye oedema
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Eye pain
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Eye swelling
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Eyelid oedema
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences all number
    0
    5
    1
    Eyelid pain
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Lacrimation increased
         subjects affected / exposed
    2 / 43 (4.65%)
    7 / 84 (8.33%)
    2 / 84 (2.38%)
         occurrences all number
    2
    7
    2
    Noninfective conjunctivitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Periorbital oedema
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 84 (3.57%)
    1 / 84 (1.19%)
         occurrences all number
    0
    4
    1
    Vision blurred
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 84 (3.57%)
    4 / 84 (4.76%)
         occurrences all number
    0
    3
    4
    Visual acuity reduced
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Visual impairment
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    1
    2
    0
    Eye irritation
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal disorders
    Anal haemorrhage
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Abdominal discomfort
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    2 / 84 (2.38%)
         occurrences all number
    0
    0
    2
    Abdominal distension
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    2 / 84 (2.38%)
         occurrences all number
    0
    1
    3
    Abdominal pain
         subjects affected / exposed
    3 / 43 (6.98%)
    6 / 84 (7.14%)
    9 / 84 (10.71%)
         occurrences all number
    4
    6
    12
    Abdominal pain lower
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    4 / 43 (9.30%)
    8 / 84 (9.52%)
    3 / 84 (3.57%)
         occurrences all number
    5
    9
    3
    Abdominal rigidity
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Aphthous ulcer
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    2
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 43 (2.33%)
    6 / 84 (7.14%)
    0 / 84 (0.00%)
         occurrences all number
    1
    6
    0
    Buccal mucosal roughening
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Chapped lips
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Cheilitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Constipation
         subjects affected / exposed
    5 / 43 (11.63%)
    11 / 84 (13.10%)
    16 / 84 (19.05%)
         occurrences all number
    5
    13
    18
    Dental cyst
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    12 / 43 (27.91%)
    37 / 84 (44.05%)
    41 / 84 (48.81%)
         occurrences all number
    21
    65
    78
    Diarrhoea haemorrhagic
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Diverticulum
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Dry mouth
         subjects affected / exposed
    1 / 43 (2.33%)
    4 / 84 (4.76%)
    3 / 84 (3.57%)
         occurrences all number
    1
    4
    3
    Dyspepsia
         subjects affected / exposed
    4 / 43 (9.30%)
    4 / 84 (4.76%)
    6 / 84 (7.14%)
         occurrences all number
    10
    4
    6
    Dysphagia
         subjects affected / exposed
    0 / 43 (0.00%)
    4 / 84 (4.76%)
    1 / 84 (1.19%)
         occurrences all number
    0
    4
    1
    Eructation
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Flatulence
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences all number
    0
    2
    1
    Gastric ulcer
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Gastritis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    1
    0
    1
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Breath odour
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Glossitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Retroperitoneal haematoma
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Haematochezia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Hiatus hernia
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperchlorhydria
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Hypoaesthesia oral
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Intra-abdominal haematoma
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Lip erosion
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Mouth haemorrhage
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Mouth ulceration
         subjects affected / exposed
    0 / 43 (0.00%)
    4 / 84 (4.76%)
    1 / 84 (1.19%)
         occurrences all number
    0
    4
    1
    Nausea
         subjects affected / exposed
    10 / 43 (23.26%)
    23 / 84 (27.38%)
    25 / 84 (29.76%)
         occurrences all number
    22
    36
    33
    Odynophagia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Oesophagitis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Oral mucosal eruption
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Oral pain
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Paraesthesia oral
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    1
    0
    Glossodynia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Steatorrhoea
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Stomatitis
         subjects affected / exposed
    5 / 43 (11.63%)
    23 / 84 (27.38%)
    11 / 84 (13.10%)
         occurrences all number
    7
    33
    11
    Tooth loss
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Toothache
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    2
    1
    0
    Vomiting
         subjects affected / exposed
    8 / 43 (18.60%)
    22 / 84 (26.19%)
    20 / 84 (23.81%)
         occurrences all number
    13
    27
    28
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Liver disorder
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Nail discolouration
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 84 (3.57%)
    1 / 84 (1.19%)
         occurrences all number
    0
    3
    1
    Acne
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Alopecia
         subjects affected / exposed
    8 / 43 (18.60%)
    15 / 84 (17.86%)
    11 / 84 (13.10%)
         occurrences all number
    8
    16
    11
    Dermatitis
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Dermatitis acneiform
         subjects affected / exposed
    1 / 43 (2.33%)
    7 / 84 (8.33%)
    9 / 84 (10.71%)
         occurrences all number
    1
    9
    18
    Dermatitis exfoliative
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Dry skin
         subjects affected / exposed
    2 / 43 (4.65%)
    16 / 84 (19.05%)
    9 / 84 (10.71%)
         occurrences all number
    2
    16
    10
    Eczema
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    1
    0
    1
    Erythema
         subjects affected / exposed
    1 / 43 (2.33%)
    5 / 84 (5.95%)
    4 / 84 (4.76%)
         occurrences all number
    1
    6
    5
    Erythema multiforme
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    2 / 84 (2.38%)
         occurrences all number
    0
    0
    2
    Hyperhidrosis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Ingrowing nail
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Intertrigo
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Madarosis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Rash pruritic
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Rash maculo-papular
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 84 (3.57%)
    0 / 84 (0.00%)
         occurrences all number
    0
    3
    0
    Skin exfoliation
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences all number
    0
    2
    1
    Rash papular
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Nail disorder
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 84 (1.19%)
    3 / 84 (3.57%)
         occurrences all number
    2
    1
    3
    Nail growth abnormal
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Nail ridging
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Night sweats
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Onychalgia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Onychoclasis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Onycholysis
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences all number
    1
    2
    1
    Onychomadesis
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    1
    2
    0
    Petechiae
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Photosensitivity reaction
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    2 / 84 (2.38%)
         occurrences all number
    0
    3
    2
    Pruritus
         subjects affected / exposed
    0 / 43 (0.00%)
    4 / 84 (4.76%)
    4 / 84 (4.76%)
         occurrences all number
    0
    4
    5
    Rash
         subjects affected / exposed
    9 / 43 (20.93%)
    29 / 84 (34.52%)
    23 / 84 (27.38%)
         occurrences all number
    10
    44
    26
    Rash erythematous
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Rash generalised
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Rash macular
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    2 / 84 (2.38%)
         occurrences all number
    0
    0
    3
    Rosacea
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Skin fissures
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    2 / 84 (2.38%)
         occurrences all number
    0
    0
    2
    Skin ulcer
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Swelling face
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Urticaria
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    2
    Xeroderma
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 43 (0.00%)
    5 / 84 (5.95%)
    1 / 84 (1.19%)
         occurrences all number
    0
    6
    1
    Acute kidney injury
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Bladder pain
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Costovertebral angle tenderness
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Oliguria
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Proteinuria
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    1
    1
    1
    Renal cyst
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Renal failure
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences all number
    0
    2
    1
    Renal impairment
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Renal infarct
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Renal vein thrombosis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Urinary retention
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    2
    0
    Pollakiuria
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    1
    0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 43 (4.65%)
    4 / 84 (4.76%)
    6 / 84 (7.14%)
         occurrences all number
    2
    5
    7
    Back pain
         subjects affected / exposed
    4 / 43 (9.30%)
    7 / 84 (8.33%)
    3 / 84 (3.57%)
         occurrences all number
    4
    7
    3
    Bone pain
         subjects affected / exposed
    2 / 43 (4.65%)
    3 / 84 (3.57%)
    0 / 84 (0.00%)
         occurrences all number
    2
    3
    0
    Joint swelling
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Limb discomfort
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Muscle spasms
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    2
    1
    0
    Muscular weakness
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 84 (3.57%)
    4 / 84 (4.76%)
         occurrences all number
    1
    3
    7
    Musculoskeletal chest pain
         subjects affected / exposed
    4 / 43 (9.30%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    4
    1
    1
    Musculoskeletal discomfort
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    1
    1
    1
    Myalgia
         subjects affected / exposed
    5 / 43 (11.63%)
    9 / 84 (10.71%)
    6 / 84 (7.14%)
         occurrences all number
    5
    10
    6
    Myopathy
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Neck pain
         subjects affected / exposed
    0 / 43 (0.00%)
    4 / 84 (4.76%)
    1 / 84 (1.19%)
         occurrences all number
    0
    4
    1
    Osteitis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Pain in extremity
         subjects affected / exposed
    6 / 43 (13.95%)
    2 / 84 (2.38%)
    4 / 84 (4.76%)
         occurrences all number
    7
    2
    5
    Spinal pain
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 84 (3.57%)
    1 / 84 (1.19%)
         occurrences all number
    0
    3
    1
    Infections and infestations
    Gastrointestinal infection
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Angular cheilitis
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    1 / 84 (1.19%)
         occurrences all number
    0
    2
    1
    Bronchitis
         subjects affected / exposed
    2 / 43 (4.65%)
    6 / 84 (7.14%)
    2 / 84 (2.38%)
         occurrences all number
    2
    6
    2
    Candida infection
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Cellulitis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Clostridium colitis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 43 (2.33%)
    5 / 84 (5.95%)
    1 / 84 (1.19%)
         occurrences all number
    1
    5
    1
    Diverticulitis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Ear infection
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    2 / 84 (2.38%)
         occurrences all number
    0
    0
    2
    Erysipelas
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    1
    0
    1
    Folliculitis
         subjects affected / exposed
    2 / 43 (4.65%)
    2 / 84 (2.38%)
    2 / 84 (2.38%)
         occurrences all number
    2
    2
    2
    Fungal skin infection
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    2
    Gingivitis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Skin infection
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    0
    2
    0
    Lung infection
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    4 / 84 (4.76%)
         occurrences all number
    0
    2
    4
    Mastitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    3 / 43 (6.98%)
    1 / 84 (1.19%)
    4 / 84 (4.76%)
         occurrences all number
    3
    1
    5
    Nosocomial infection
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Ophthalmic herpes zoster
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Oral candidiasis
         subjects affected / exposed
    3 / 43 (6.98%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    4
    1
    1
    Oral fungal infection
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    4 / 84 (4.76%)
         occurrences all number
    0
    2
    5
    Oral infection
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Paronychia
         subjects affected / exposed
    1 / 43 (2.33%)
    7 / 84 (8.33%)
    1 / 84 (1.19%)
         occurrences all number
    1
    9
    1
    Peritonitis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Pharyngitis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Pneumonia
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 84 (3.57%)
    4 / 84 (4.76%)
         occurrences all number
    1
    3
    4
    Rash pustular
         subjects affected / exposed
    0 / 43 (0.00%)
    5 / 84 (5.95%)
    1 / 84 (1.19%)
         occurrences all number
    0
    7
    1
    Respiratory tract infection
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    1
    1
    1
    Respiratory tract infection bacterial
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Rhinitis
         subjects affected / exposed
    2 / 43 (4.65%)
    3 / 84 (3.57%)
    1 / 84 (1.19%)
         occurrences all number
    2
    3
    1
    Septic shock
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Laryngitis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Staphylococcal infection
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    1
    1
    0
    Urinary tract infection
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 84 (1.19%)
    5 / 84 (5.95%)
         occurrences all number
    2
    1
    7
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    1
    0
    1
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Wound infection
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Metabolism and nutrition disorders
    Abnormal loss of weight
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Central obesity
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    0 / 84 (0.00%)
         occurrences all number
    0
    1
    0
    Decreased appetite
         subjects affected / exposed
    10 / 43 (23.26%)
    18 / 84 (21.43%)
    21 / 84 (25.00%)
         occurrences all number
    10
    20
    21
    Dehydration
         subjects affected / exposed
    1 / 43 (2.33%)
    4 / 84 (4.76%)
    4 / 84 (4.76%)
         occurrences all number
    1
    4
    4
    Diabetes mellitus
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    0 / 84 (0.00%)
         occurrences all number
    1
    0
    0
    Fluid overload
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    2
    Hypercalcaemia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Hyperglycaemia
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    2
    1
    1
    Hyperkalaemia
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 84 (2.38%)
    0 / 84 (0.00%)
         occurrences all number
    0
    3
    0
    Hyperphosphataemia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 43 (4.65%)
    2 / 84 (2.38%)
    3 / 84 (3.57%)
         occurrences all number
    3
    3
    3
    Hypocalcaemia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1
    Hypoglycaemia
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 84 (1.19%)
    1 / 84 (1.19%)
         occurrences all number
    0
    1
    1
    Hyponatraemia
         subjects affected / exposed
    1 / 43 (2.33%)
    4 / 84 (4.76%)
    1 / 84 (1.19%)
         occurrences all number
    1
    4
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 84 (2.38%)
    5 / 84 (5.95%)
         occurrences all number
    1
    2
    5
    Hypoproteinaemia
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    1
    0
    1
    Vitamin K deficiency
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    2 / 84 (2.38%)
         occurrences all number
    0
    0
    2
    Hypomagnesaemia
         subjects affected / exposed
    3 / 43 (6.98%)
    2 / 84 (2.38%)
    3 / 84 (3.57%)
         occurrences all number
    3
    3
    4
    Hypophagia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 84 (0.00%)
    1 / 84 (1.19%)
         occurrences all number
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Mar 2013
    All participating patients were to receive primary prophylactic G CSF
    10 Dec 2013
    Prospective central KRAS testing was added
    28 Jul 2014
    Benefit/risk and ethical assessment amended

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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