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    Clinical Trial Results:
    A double-blind placebo controlled randomized trial of PF-804 in patients with incurable stage IIIB/IV non-small cell lung cancer after failure of standard therapy for advanced or metastatic disease.

    Summary
    EudraCT number
    		 2009-016509-41
    Trial protocol
    		 IT  
    Global end of trial date
    16 Jul 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Jul 2016
    First version publication date
    29 Jul 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    BR.26
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01000025
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    WWCR WORLDWIDE CLINICAL RESEARCH
    Sponsor organisation address
    Duite 1010, Overland Park - KS66210 -, Lowell-US, United States, 10955
    Public contact
    Barbara GEIGER, WWCR WORLDWIDE CLINICAL RESEARCH, bgeiger@clinipace.com
    Scientific contact
    Barbara GEIGER, WWCR WORLDWIDE CLINICAL RESEARCH, bgeiger@clinipace.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
    01 Jan 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Oct 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Jul 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare overall survival (OS) between the 2 arms
    Protection of trial subjects
    NA
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Dec 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Italy: 111
    Country: Number of subjects enrolled
    Canada: 308
    Country: Number of subjects enrolled
    Korea, Republic of: 71
    Country: Number of subjects enrolled
    Philippines: 31
    Country: Number of subjects enrolled
    Thailand: 42
    Country: Number of subjects enrolled
    Australia: 77
    Country: Number of subjects enrolled
    Brazil: 39
    Country: Number of subjects enrolled
    Taiwan: 17
    Country: Number of subjects enrolled
    Argentina: 10
    Country: Number of subjects enrolled
    Peru: 1
    Country: Number of subjects enrolled
    United States: 2
    Country: Number of subjects enrolled
    New Zealand: 11
    Worldwide total number of subjects
    720
    EEA total number of subjects
    111
    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)
    373
    From 65 to 84 years
    347
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 No text enterd

    Pre-assignment
    Screening details
    		 no text entered

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 PF-804
    Arm description
    		 Study treatment arm
    Arm type
    		 Experimental

    Investigational medicinal product name
    PF-00299804
    Investigational medicinal product code
    Other name
    Dacomitinib
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    45 mg PO, daily, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

    Arm title
    		 Placebo
    Arm description
    		 Control Arm
    Arm type
    		 Placebo

    Investigational medicinal product name
    PF-00299804
    Investigational medicinal product code
    Other name
    Dacomitinib
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    45 mg PO, daily, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

    Number of subjects in period 1
    		PF-804 Placebo
    Started
    480
    240
    Completed
    12
    2
    Not completed
    468
    238
         Consent withdrawn by subject
    13
    8
         Adverse event, non-fatal
    43
    2
         Death
    23
    13
         Intercurrent Illness
    26
    7
         Lack of efficacy
    363
    208

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    PF-804
    Reporting group description
    		 Study treatment arm

    Reporting group title
    Placebo
    Reporting group description
    		 Control Arm

    Reporting group values
    		 PF-804 Placebo Total
    Number of subjects
    		 480 240 720
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 63.5 (32 to 86) 65.5 (34 to 90) -
    Gender categorical
    Units: Subjects
        Female
    		 236 120 356
        Male
    		 244 120 364
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 2 0 2
        Asian
    		 172 87 259
        Native Hawaiian or Other Pacific Islander
    		 1 0 1
        Black or African American
    		 4 1 5
        White
    		 288 144 432
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 13 8 21
    Region of Enrollment
    Units: Subjects
        United States
    		 1 1 2
        Philippines
    		 20 11 31
        Taiwan
    		 11 6 17
        Canada
    		 207 101 308
        Thailand
    		 28 14 42
        Brazil
    		 25 14 39
        Peru
    		 0 1 1
        Australia
    		 50 27 77
        New Zealand
    		 7 4 11
        Italy
    		 77 34 111
        Korea, Republic of
    		 47 24 71
        Argentina
    		 7 3 10

    End points

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    End points reporting groups
    Reporting group title
    PF-804
    Reporting group description
    		 Study treatment arm

    Reporting group title
    Placebo
    Reporting group description
    		 Control Arm

    Primary: Overall survival

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    End point title
    		 Overall survival
    End point description
    ITT
    End point type
    Primary
    End point timeframe
    42 months
    End point values
    		 PF-804 Placebo
    Number of subjects analysed
    480
    240
    Units: Months
        median (confidence interval 95%)
    6.83 (6.08 to 7.49)
    6.31 (5.32 to 7.52)
    Statistical analysis title
    		 Overall Survival
    Statistical analysis description
    The trial was designed to detect a 25% deduction in risk of death with PF-804 with 90% power using a 1-sided 2.5% level significance test. The sample size was estimated as 720 patients.
    Comparison groups
    PF-804 v Placebo
    Number of subjects included in analysis
    720
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.506
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 1.21

    Secondary: Overall Survival in KRAS-WT Patients

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    End point title
    		 Overall Survival in KRAS-WT Patients
    End point description
    Patients with K-Ras mutation wild type
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 PF-804 Placebo
    Number of subjects analysed
    220
    120
    Units: Months
        median (confidence interval 95%)
    7 (6.01 to 8.21)
    5.19 (4.53 to 7)
    Statistical analysis title
    		 Overall Survival in KRAS-WT Patients
    Comparison groups
    PF-804 v Placebo
    Number of subjects included in analysis
    340
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.043
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 1.03

    Secondary: Overall Survival in EGFR-mutant Patients

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    End point title
    		 Overall Survival in EGFR-mutant Patients
    End point description
    Patients with EGFR mutation
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 PF-804 Placebo
    Number of subjects analysed
    114
    68
    Units: Months
        median (confidence interval 95%)
    7.23 (6.08 to 8.61)
    7.52 (4.99 to 9.49)
    Statistical analysis title
    		 Overall Survival in EGFR-mutant Patients
    Comparison groups
    PF-804 v Placebo
    Number of subjects included in analysis
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.46
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 1.44

    Secondary: Progression-free Survival

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    End point title
    		 Progression-free Survival
    End point description
    ITT
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 PF-804 Placebo
    Number of subjects analysed
    480
    240
    Units: Months
        median (confidence interval 95%)
    2.66 (1.91 to 3.32)
    1.58 (0.99 to 1.74)
    Statistical analysis title
    		 Progression-free Survival
    Comparison groups
    PF-804 v Placebo
    Number of subjects included in analysis
    720
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Log hazard ratio
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 0.79

    Secondary: Objective Response Rate

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    End point title
    		 Objective Response Rate
    End point description
    ITT
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 PF-804 Placebo
    Number of subjects analysed
    480
    240
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    7.1 (4.8 to 9.4)
    1.3 (0 to 2.7)
    Statistical analysis title
    		 Objective Response Rate
    Comparison groups
    PF-804 v Placebo
    Number of subjects included in analysis
    720
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    6.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.84
         upper limit
    		 20.3

    Secondary: Number of Participants With Toxicity as Measured by NCI CTCAE Version 4.0

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    End point title
    		 Number of Participants With Toxicity as Measured by NCI CTCAE Version 4.0
    End point description
    As treated population
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 PF-804 Placebo
    Number of subjects analysed
    477
    239
    Units: Number of Participants
    467
    223
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    42 months
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 NCI CTCAE
    Dictionary version
    4
    Reporting groups
    Reporting group title
    PF-804
    Reporting group description
    		 Study treatment arm

    Reporting group title
    Placebo
    Reporting group description
    		 Control Arm

    Serious adverse events
    		 PF-804 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    187 / 477 (39.20%)
    86 / 239 (35.98%)
         number of deaths (all causes)
    3
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasm progression
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    76 / 477 (15.93%)
    42 / 239 (17.57%)
         occurrences causally related to treatment / all
    0 / 77
    0 / 42
         deaths causally related to treatment / all
    0 / 72
    0 / 37
    Non-small cell lung cancer metastatic
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thromboembolic event
         subjects affected / exposed
    12 / 477 (2.52%)
    3 / 239 (1.26%)
         occurrences causally related to treatment / all
    3 / 12
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death NOS
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Gait disturbance
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion site extravasation
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death NOS
         subjects affected / exposed
    1 / 477 (0.21%)
    2 / 239 (0.84%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Extravasation
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    9 / 477 (1.89%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    2 / 9
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden Death
         subjects affected / exposed
    1 / 477 (0.21%)
    2 / 239 (0.84%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Aspiration
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchopulmonary hemorrhage
         subjects affected / exposed
    6 / 477 (1.26%)
    4 / 239 (1.67%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dyspnea
         subjects affected / exposed
    27 / 477 (5.66%)
    14 / 239 (5.86%)
         occurrences causally related to treatment / all
    0 / 31
    0 / 17
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Epistaxis
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    4 / 477 (0.84%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    8 / 477 (1.68%)
    3 / 239 (1.26%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumotorax
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Productive cough
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary Edema
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory Failure
         subjects affected / exposed
    6 / 477 (1.26%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 2
         deaths causally related to treatment / all
    2 / 2
    0 / 1
    Dysphonia
         subjects affected / exposed
    27 / 477 (5.66%)
    14 / 239 (5.86%)
         occurrences causally related to treatment / all
    0 / 31
    0 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nasal inflammation
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusion
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Personality change
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Neutrophil count decresead
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight Loss
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 477 (0.21%)
    2 / 239 (0.84%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cognitive Disturbance
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    4 / 477 (0.84%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalothy
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial hemorrhage
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ischemia cerebrovascular
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paresthesia
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizures
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus headache
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischemic attacks
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 477 (0.42%)
    3 / 239 (1.26%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Spinal cord compression
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Hearing impaired
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Corneal ulcer
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    4 / 477 (0.84%)
    3 / 239 (1.26%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal Hemorrhage
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhea
         subjects affected / exposed
    17 / 477 (3.56%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    18 / 20
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 477 (0.00%)
    2 / 239 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Esophageal stenosis
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal pain
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    5 / 477 (1.05%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    3 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obstruction Gastric
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small Intestinal Obstruction
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper Gastrointestinal Hemorrhage
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    8 / 477 (1.68%)
    3 / 239 (1.26%)
         occurrences causally related to treatment / all
    7 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    4 / 477 (0.84%)
    2 / 239 (0.84%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash acneiform
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stevens-Johnson syndrome
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    6 / 477 (1.26%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    4 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 477 (0.42%)
    2 / 239 (0.84%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest wall pain
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalized muscle weakness
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertrophic osteoarthropathy
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchial Infection
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis Infectious
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung Infection
         subjects affected / exposed
    31 / 477 (6.50%)
    12 / 239 (5.02%)
         occurrences causally related to treatment / all
    2 / 35
    0 / 14
         deaths causally related to treatment / all
    0 / 4
    0 / 3
    Lymph gland infection
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal Infection
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Other Infections and Infestation
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scrotal infection
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 477 (0.42%)
    3 / 239 (1.26%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Skin infection
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Folliculitis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    16 / 477 (3.35%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    9 / 16
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypercalcemia
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycemia
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalemia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyponatremia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 PF-804 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    465 / 477 (97.48%)
    219 / 239 (91.63%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor Pain
         subjects affected / exposed
    5 / 477 (1.05%)
    3 / 239 (1.26%)
         occurrences all number
    5
    3
    Vascular disorders
    Embolism
         subjects affected / exposed
    10 / 477 (2.10%)
    7 / 239 (2.93%)
         occurrences all number
    10
    7
    Flushing
         subjects affected / exposed
    4 / 477 (0.84%)
    2 / 239 (0.84%)
         occurrences all number
    5
    2
    Haematoma
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Hot flush
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Hypertension
         subjects affected / exposed
    2 / 477 (0.42%)
    4 / 239 (1.67%)
         occurrences all number
    2
    4
    Hypotension
         subjects affected / exposed
    8 / 477 (1.68%)
    2 / 239 (0.84%)
         occurrences all number
    8
    2
    Lymphoedema
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Peripheral coldness
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    1
    Phlebitis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Thrombophlebitis superficial
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Surgical and medical procedures
    Ear operation
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Nail operation
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    20 / 477 (4.19%)
    4 / 239 (1.67%)
         occurrences all number
    20
    4
    Death
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Early satiety
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    2
    1
    Face oedema
         subjects affected / exposed
    4 / 477 (0.84%)
    0 / 239 (0.00%)
         occurrences all number
    4
    0
    Fatigue
         subjects affected / exposed
    164 / 477 (34.38%)
    62 / 239 (25.94%)
         occurrences all number
    177
    64
    Gait disturbance
         subjects affected / exposed
    4 / 477 (0.84%)
    6 / 239 (2.51%)
         occurrences all number
    4
    6
    Influenza like illness
         subjects affected / exposed
    7 / 477 (1.47%)
    9 / 239 (3.77%)
         occurrences all number
    9
    11
    Localised oedema
         subjects affected / exposed
    2 / 477 (0.42%)
    2 / 239 (0.84%)
         occurrences all number
    2
    2
    Malaise
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences all number
    3
    1
    Mass
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Non-cardiac chest pain
         subjects affected / exposed
    19 / 477 (3.98%)
    8 / 239 (3.35%)
         occurrences all number
    20
    8
    Oedema peripheral
         subjects affected / exposed
    34 / 477 (7.13%)
    21 / 239 (8.79%)
         occurrences all number
    41
    21
    Pain
         subjects affected / exposed
    33 / 477 (6.92%)
    23 / 239 (9.62%)
         occurrences all number
    34
    23
    Pyrexia
         subjects affected / exposed
    38 / 477 (7.97%)
    13 / 239 (5.44%)
         occurrences all number
    42
    13
    Reproductive system and breast disorders
    Balanoposthitis
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Erectile dysfunction
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Menstruation irregular
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Pelvic pain
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Vaginal discharge
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Vaginal inflammation
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences all number
    4
    0
    Vulvovaginal dryness
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Vulvovaginal pain
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Bronchial obstruction
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Cough
         subjects affected / exposed
    69 / 477 (14.47%)
    35 / 239 (14.64%)
         occurrences all number
    71
    35
    Dysphonia
         subjects affected / exposed
    20 / 477 (4.19%)
    5 / 239 (2.09%)
         occurrences all number
    21
    5
    Dyspnoea
         subjects affected / exposed
    105 / 477 (22.01%)
    53 / 239 (22.18%)
         occurrences all number
    106
    59
    Haemoptysis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Epistaxis
         subjects affected / exposed
    71 / 477 (14.88%)
    3 / 239 (1.26%)
         occurrences all number
    79
    6
    Haemothorax
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Hiccups
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Hypoxia
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Laryngeal haemorrhage
         subjects affected / exposed
    5 / 477 (1.05%)
    4 / 239 (1.67%)
         occurrences all number
    5
    5
    Laryngeal inflammation
         subjects affected / exposed
    4 / 477 (0.84%)
    0 / 239 (0.00%)
         occurrences all number
    4
    0
    Laryngeal pain
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Nasal congestion
         subjects affected / exposed
    13 / 477 (2.73%)
    1 / 239 (0.42%)
         occurrences all number
    13
    1
    Nasal dryness
         subjects affected / exposed
    6 / 477 (1.26%)
    1 / 239 (0.42%)
         occurrences all number
    7
    1
    Nasal inflammation
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Oropharyngeal pain
         subjects affected / exposed
    25 / 477 (5.24%)
    3 / 239 (1.26%)
         occurrences all number
    28
    3
    Pharyngeal haemorrhage
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    2
    Pharyngeal inflammation
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Pleural effusion
         subjects affected / exposed
    0 / 477 (0.00%)
    2 / 239 (0.84%)
         occurrences all number
    0
    2
    Pleuritic pain
         subjects affected / exposed
    2 / 477 (0.42%)
    4 / 239 (1.67%)
         occurrences all number
    2
    4
    Pneumonitis
         subjects affected / exposed
    4 / 477 (0.84%)
    1 / 239 (0.42%)
         occurrences all number
    8
    1
    Pneumothorax
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Productive cough
         subjects affected / exposed
    25 / 477 (5.24%)
    18 / 239 (7.53%)
         occurrences all number
    29
    20
    Pulmonary haemorrhage
         subjects affected / exposed
    20 / 477 (4.19%)
    10 / 239 (4.18%)
         occurrences all number
    21
    11
    Respiratory failure
         subjects affected / exposed
    4 / 477 (0.84%)
    0 / 239 (0.00%)
         occurrences all number
    4
    0
    Rhinitis allergic
         subjects affected / exposed
    9 / 477 (1.89%)
    4 / 239 (1.67%)
         occurrences all number
    10
    4
    Rhinorrhoea
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Sinus disorder
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Sneezing
         subjects affected / exposed
    4 / 477 (0.84%)
    0 / 239 (0.00%)
         occurrences all number
    4
    0
    Stridor
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Tracheal inflammation
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    18 / 477 (3.77%)
    2 / 239 (0.84%)
         occurrences all number
    18
    3
    wheezing
         subjects affected / exposed
    2 / 477 (0.42%)
    2 / 239 (0.84%)
         occurrences all number
    2
    2
    Psychiatric disorders
    Abnormal dreams
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Agitation
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    2
    2
    Anxiety
         subjects affected / exposed
    12 / 477 (2.52%)
    5 / 239 (2.09%)
         occurrences all number
    13
    5
    Confusional state
         subjects affected / exposed
    4 / 477 (0.84%)
    2 / 239 (0.84%)
         occurrences all number
    4
    2
    Delirium
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    1
    Depression
         subjects affected / exposed
    10 / 477 (2.10%)
    5 / 239 (2.09%)
         occurrences all number
    10
    5
    Hallucination
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Insomnia
         subjects affected / exposed
    33 / 477 (6.92%)
    12 / 239 (5.02%)
         occurrences all number
    33
    13
    Irritability
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Personality change
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Restlessness
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Suicidal ideation
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Amylase increased
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    International normalised ratio increased
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences all number
    3
    1
    Prostatic specific antigen increased
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Weight decresed
         subjects affected / exposed
    62 / 477 (13.00%)
    15 / 239 (6.28%)
         occurrences all number
    67
    15
    Injury, poisoning and procedural complications
    Anastomotic ulcer
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Contusion
         subjects affected / exposed
    6 / 477 (1.26%)
    3 / 239 (1.26%)
         occurrences all number
    6
    3
    Corneal abrasion
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Ear abrasion
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Fall
         subjects affected / exposed
    7 / 477 (1.47%)
    0 / 239 (0.00%)
         occurrences all number
    7
    0
    Gastrointestinal stoma complication
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Fracture
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Ligament sprain
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Skin abrasion
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Thermal Burn
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Wound dehiscence
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    2
    Congenital, familial and genetic disorders
    Distichiasis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    2
    1
    Cardiac tamponade
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Myocardial infarction
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Palpitations
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    1
    Pericardial Effusion
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Sinus Tachycardia
         subjects affected / exposed
    7 / 477 (1.47%)
    2 / 239 (0.84%)
         occurrences all number
    7
    2
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Ventricular arrythmia
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    1
    Ventricular tachycardia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Aphasia
         subjects affected / exposed
    2 / 477 (0.42%)
    5 / 239 (2.09%)
         occurrences all number
    2
    5
    Aphonia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Ataxia
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Cerebral ischaemia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    cerebrovascular accident
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Cognitive disorder
         subjects affected / exposed
    2 / 477 (0.42%)
    2 / 239 (0.84%)
         occurrences all number
    2
    2
    Disturbance in attention
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    2
    1
    dizziness
         subjects affected / exposed
    44 / 477 (9.22%)
    17 / 239 (7.11%)
         occurrences all number
    47
    19
    Dysarthria
         subjects affected / exposed
    1 / 477 (0.21%)
    2 / 239 (0.84%)
         occurrences all number
    1
    2
    Dysgeusia
         subjects affected / exposed
    32 / 477 (6.71%)
    3 / 239 (1.26%)
         occurrences all number
    34
    3
    Dyskinesia
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences all number
    3
    1
    Encephalopathy
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    glossopharyngeal nerve disorder
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    33 / 477 (6.92%)
    16 / 239 (6.69%)
         occurrences all number
    41
    16
    Hemiparesis
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    1
    Hypoaesthesia
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Lethargy
         subjects affected / exposed
    2 / 477 (0.42%)
    2 / 239 (0.84%)
         occurrences all number
    2
    2
    Neuralgia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia
         subjects affected / exposed
    12 / 477 (2.52%)
    1 / 239 (0.42%)
         occurrences all number
    12
    1
    Parosmia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Peripheral motor neuropathy
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences all number
    3
    1
    Peripheral sensory neuropathy
         subjects affected / exposed
    23 / 477 (4.82%)
    8 / 239 (3.35%)
         occurrences all number
    23
    8
    Presyncope
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Seizure
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences all number
    6
    1
    Somnolence
         subjects affected / exposed
    6 / 477 (1.26%)
    3 / 239 (1.26%)
         occurrences all number
    6
    3
    Syncope
         subjects affected / exposed
    4 / 477 (0.84%)
    1 / 239 (0.42%)
         occurrences all number
    6
    1
    Tremor
         subjects affected / exposed
    4 / 477 (0.84%)
    2 / 239 (0.84%)
         occurrences all number
    4
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Leukocytosis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Ear disorder
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Ear pain
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences all number
    3
    1
    Hearing impaired
         subjects affected / exposed
    2 / 477 (0.42%)
    3 / 239 (1.26%)
         occurrences all number
    2
    3
    Middle ear inflammation
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Tinnitus
         subjects affected / exposed
    3 / 477 (0.63%)
    2 / 239 (0.84%)
         occurrences all number
    3
    2
    Vertigo
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    2
    1
    Vestibular disorder
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Eye disorders
    Dry eye
         subjects affected / exposed
    37 / 477 (7.76%)
    1 / 239 (0.42%)
         occurrences all number
    38
    1
    Blepharitis
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Cataract
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Conjunctival haemorrhage
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Diplopia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    eye pain
         subjects affected / exposed
    10 / 477 (2.10%)
    1 / 239 (0.42%)
         occurrences all number
    11
    1
    Eye pruritus
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Keratitis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Lacrimation increased
         subjects affected / exposed
    13 / 477 (2.73%)
    1 / 239 (0.42%)
         occurrences all number
    14
    1
    Periorbital oedema
         subjects affected / exposed
    0 / 477 (0.00%)
    3 / 239 (1.26%)
         occurrences all number
    0
    3
    Photophobia
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Trichiasis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Ulcerative keratitis
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Vision blurred
         subjects affected / exposed
    19 / 477 (3.98%)
    0 / 239 (0.00%)
         occurrences all number
    21
    0
    Visual acuity reduced
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Vitreous floaters
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal disorders
    Diarrhea
         subjects affected / exposed
    371 / 477 (77.78%)
    41 / 239 (17.15%)
         occurrences all number
    576
    54
    Dry mouth
         subjects affected / exposed
    45 / 477 (9.43%)
    7 / 239 (2.93%)
         occurrences all number
    49
    8
    Dyspepsia
         subjects affected / exposed
    20 / 477 (4.19%)
    3 / 239 (1.26%)
         occurrences all number
    20
    3
    Gastroesophageal reflux disease
         subjects affected / exposed
    16 / 477 (3.35%)
    8 / 239 (3.35%)
         occurrences all number
    17
    8
    Abdominal pain
         subjects affected / exposed
    43 / 477 (9.01%)
    14 / 239 (5.86%)
         occurrences all number
    47
    14
    Abdominal pain upper
         subjects affected / exposed
    5 / 477 (1.05%)
    3 / 239 (1.26%)
         occurrences all number
    5
    3
    Aerophagia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Anal haemorrhage
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Ascites
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    2
    1
    Anal Inflammation
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences all number
    3
    1
    Chapped lips
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Cheilitis
         subjects affected / exposed
    18 / 477 (3.77%)
    0 / 239 (0.00%)
         occurrences all number
    20
    0
    Constipation
         subjects affected / exposed
    53 / 477 (11.11%)
    38 / 239 (15.90%)
         occurrences all number
    55
    43
    Dental Caries
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Duodenal ulcer
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Dysphagia
         subjects affected / exposed
    13 / 477 (2.73%)
    5 / 239 (2.09%)
         occurrences all number
    14
    5
    Eructation
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    1
    Flatulence
         subjects affected / exposed
    5 / 477 (1.05%)
    2 / 239 (0.84%)
         occurrences all number
    5
    2
    Gastritis
         subjects affected / exposed
    6 / 477 (1.26%)
    1 / 239 (0.42%)
         occurrences all number
    7
    1
    Gatrointestinal pain
         subjects affected / exposed
    0 / 477 (0.00%)
    2 / 239 (0.84%)
         occurrences all number
    0
    2
    Gengival pain
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    4 / 477 (0.84%)
    0 / 239 (0.00%)
         occurrences all number
    4
    0
    Haemorrhoids
         subjects affected / exposed
    5 / 477 (1.05%)
    0 / 239 (0.00%)
         occurrences all number
    7
    0
    Hypoaesthesia oral
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Lip pain
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Mouth haemorrhage
         subjects affected / exposed
    5 / 477 (1.05%)
    1 / 239 (0.42%)
         occurrences all number
    5
    1
    Nausea
         subjects affected / exposed
    139 / 477 (29.14%)
    41 / 239 (17.15%)
         occurrences all number
    169
    51
    Oesophageal pain
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Oesophagitis
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Oral dysaesthesia
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Oral pain
         subjects affected / exposed
    9 / 477 (1.89%)
    3 / 239 (1.26%)
         occurrences all number
    12
    3
    Periodontal disease
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Proctalgia
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Rectal haemorrhage
         subjects affected / exposed
    6 / 477 (1.26%)
    0 / 239 (0.00%)
         occurrences all number
    6
    0
    Salivary duct inflammation
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Salivary hypersecretion
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Stomatitis
         subjects affected / exposed
    203 / 477 (42.56%)
    7 / 239 (2.93%)
         occurrences all number
    235
    7
    Tongue discolouration
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Tongue ulceration
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    2
    1
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    126 / 477 (26.42%)
    29 / 239 (12.13%)
         occurrences all number
    180
    42
    Hepatobiliary disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    2
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    8 / 477 (1.68%)
    3 / 239 (1.26%)
         occurrences all number
    8
    3
    Dermatitis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Dermatitis acneiform
         subjects affected / exposed
    270 / 477 (56.60%)
    20 / 239 (8.37%)
         occurrences all number
    308
    23
    Dermatitis bullous
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Dry skin
         subjects affected / exposed
    139 / 477 (29.14%)
    16 / 239 (6.69%)
         occurrences all number
    155
    17
    Erythema multiforme
         subjects affected / exposed
    13 / 477 (2.73%)
    1 / 239 (0.42%)
         occurrences all number
    14
    1
    Excessive granulation tissue
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Hair colour changes
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Hair growth abnormal
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Hair texture abnormal
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Hirsutism
         subjects affected / exposed
    4 / 477 (0.84%)
    0 / 239 (0.00%)
         occurrences all number
    4
    0
    Hyperhidrosis
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    2
    1
    Hypertrichosis
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences all number
    3
    1
    Ingrowing nail
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Koilonychia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Madarosis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Nail discolouration
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Nail disorder
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Nail ridging
         subjects affected / exposed
    5 / 477 (1.05%)
    0 / 239 (0.00%)
         occurrences all number
    5
    0
    Onychoclasis
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    3
    1
    Onychomadesis
         subjects affected / exposed
    4 / 477 (0.84%)
    0 / 239 (0.00%)
         occurrences all number
    4
    0
    Pain of skin
         subjects affected / exposed
    7 / 477 (1.47%)
    0 / 239 (0.00%)
         occurrences all number
    8
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    55 / 477 (11.53%)
    2 / 239 (0.84%)
         occurrences all number
    55
    2
    Pruritus
         subjects affected / exposed
    79 / 477 (16.56%)
    20 / 239 (8.37%)
         occurrences all number
    97
    25
    Purpura
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    73 / 477 (15.30%)
    14 / 239 (5.86%)
         occurrences all number
    80
    14
    Scab
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Skin atrophy
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Skin disorder
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Skin exfoliation
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Skin fissures
         subjects affected / exposed
    16 / 477 (3.35%)
    0 / 239 (0.00%)
         occurrences all number
    20
    0
    Skin hyperpigmentation
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Skin induration
         subjects affected / exposed
    2 / 477 (0.42%)
    2 / 239 (0.84%)
         occurrences all number
    2
    2
    Skin ulcer
         subjects affected / exposed
    21 / 477 (4.40%)
    3 / 239 (1.26%)
         occurrences all number
    24
    3
    Stevens-Johnson syndrome
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Telangiectasia
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Urticaria
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Chromaturia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Cystitis noninfective
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Glycosuria
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    2
    Haematuria
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Micturition urgency
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    1
    Nephrolithiasis
         subjects affected / exposed
    0 / 477 (0.00%)
    2 / 239 (0.84%)
         occurrences all number
    0
    2
    Pollakiuria
         subjects affected / exposed
    1 / 477 (0.21%)
    2 / 239 (0.84%)
         occurrences all number
    1
    2
    proteinuria
         subjects affected / exposed
    7 / 477 (1.47%)
    1 / 239 (0.42%)
         occurrences all number
    9
    1
    Urinary incontinence
         subjects affected / exposed
    2 / 477 (0.42%)
    2 / 239 (0.84%)
         occurrences all number
    2
    2
    Urinary retention
         subjects affected / exposed
    6 / 477 (1.26%)
    0 / 239 (0.00%)
         occurrences all number
    6
    0
    Urinary tract pain
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences all number
    3
    1
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    1
    Cushingoid
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 477 (0.21%)
    1 / 239 (0.42%)
         occurrences all number
    1
    1
    Arthritis
         subjects affected / exposed
    2 / 477 (0.42%)
    2 / 239 (0.84%)
         occurrences all number
    3
    2
    Back pain
         subjects affected / exposed
    32 / 477 (6.71%)
    17 / 239 (7.11%)
         occurrences all number
    35
    17
    Bone pain
         subjects affected / exposed
    15 / 477 (3.14%)
    10 / 239 (4.18%)
         occurrences all number
    15
    10
    flank pain
         subjects affected / exposed
    5 / 477 (1.05%)
    3 / 239 (1.26%)
         occurrences all number
    5
    3
    Groin pain
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Hypertrophic osteoarthropathy
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Joint range of motion decreased
         subjects affected / exposed
    2 / 477 (0.42%)
    2 / 239 (0.84%)
         occurrences all number
    2
    2
    Muscular weakness
         subjects affected / exposed
    25 / 477 (5.24%)
    7 / 239 (2.93%)
         occurrences all number
    25
    7
    Musculoskeletal pain
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    2
    1
    Myalgia
         subjects affected / exposed
    10 / 477 (2.10%)
    6 / 239 (2.51%)
         occurrences all number
    12
    7
    Neck pain
         subjects affected / exposed
    2 / 477 (0.42%)
    7 / 239 (2.93%)
         occurrences all number
    3
    8
    Pain in extremity
         subjects affected / exposed
    39 / 477 (8.18%)
    19 / 239 (7.95%)
         occurrences all number
    43
    20
    Periarthritis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Anorectal infection
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Bronchitis
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences all number
    4
    1
    Conjunctivitis
         subjects affected / exposed
    50 / 477 (10.48%)
    0 / 239 (0.00%)
         occurrences all number
    59
    0
    Cystitis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Enterocolitis infectious
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Eye infection
         subjects affected / exposed
    5 / 477 (1.05%)
    0 / 239 (0.00%)
         occurrences all number
    6
    0
    Eyelid infection
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Furuncle
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Gingivitis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Herpes zoster
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Laryngitis
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Lip infection
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Lung infection
         subjects affected / exposed
    21 / 477 (4.40%)
    5 / 239 (2.09%)
         occurrences all number
    22
    5
    Mucosal infection
         subjects affected / exposed
    11 / 477 (2.31%)
    4 / 239 (1.67%)
         occurrences all number
    11
    4
    Nail infection
         subjects affected / exposed
    11 / 477 (2.31%)
    0 / 239 (0.00%)
         occurrences all number
    12
    0
    Otitis externa
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Otitis media
         subjects affected / exposed
    3 / 477 (0.63%)
    0 / 239 (0.00%)
         occurrences all number
    3
    0
    Paronychia
         subjects affected / exposed
    138 / 477 (28.93%)
    0 / 239 (0.00%)
         occurrences all number
    154
    0
    Pharyngitis
         subjects affected / exposed
    2 / 477 (0.42%)
    0 / 239 (0.00%)
         occurrences all number
    2
    0
    Rash pustular
         subjects affected / exposed
    11 / 477 (2.31%)
    1 / 239 (0.42%)
         occurrences all number
    15
    1
    Rhinitis
         subjects affected / exposed
    5 / 477 (1.05%)
    0 / 239 (0.00%)
         occurrences all number
    5
    0
    Scrotal infection
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Skin infection
         subjects affected / exposed
    22 / 477 (4.61%)
    2 / 239 (0.84%)
         occurrences all number
    23
    2
    Soft tissue infection
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Stoma site infection
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    2
    1
    Tooth Infection
         subjects affected / exposed
    0 / 477 (0.00%)
    2 / 239 (0.84%)
         occurrences all number
    0
    2
    Tracheitis
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    17 / 477 (3.56%)
    6 / 239 (2.51%)
         occurrences all number
    19
    7
    Urinary tract infection
         subjects affected / exposed
    15 / 477 (3.14%)
    8 / 239 (3.35%)
         occurrences all number
    21
    8
    Vaginal infection
         subjects affected / exposed
    2 / 477 (0.42%)
    1 / 239 (0.42%)
         occurrences all number
    2
    1
    Wound infection
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0
    Decreased appetite
         subjects affected / exposed
    147 / 477 (30.82%)
    51 / 239 (21.34%)
         occurrences all number
    156
    54
    Dehydration
         subjects affected / exposed
    16 / 477 (3.35%)
    3 / 239 (1.26%)
         occurrences all number
    17
    3
    Hypercalcaemia
         subjects affected / exposed
    3 / 477 (0.63%)
    1 / 239 (0.42%)
         occurrences all number
    3
    1
    Hyperglycaemia
         subjects affected / exposed
    3 / 477 (0.63%)
    2 / 239 (0.84%)
         occurrences all number
    3
    2
    Hyperkalaemia
         subjects affected / exposed
    0 / 477 (0.00%)
    1 / 239 (0.42%)
         occurrences all number
    0
    1
    Hypoglycaemia
         subjects affected / exposed
    3 / 477 (0.63%)
    2 / 239 (0.84%)
         occurrences all number
    3
    3
    Hypokalaemia
         subjects affected / exposed
    5 / 477 (1.05%)
    3 / 239 (1.26%)
         occurrences all number
    5
    3
    Hypomagnesaemia
         subjects affected / exposed
    4 / 477 (0.84%)
    3 / 239 (1.26%)
         occurrences all number
    4
    3
    Hyponatraemia
         subjects affected / exposed
    1 / 477 (0.21%)
    4 / 239 (1.67%)
         occurrences all number
    1
    4
    Hypophosphataemia
         subjects affected / exposed
    1 / 477 (0.21%)
    0 / 239 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Jul 2011
    AMENDMENT #1: 2011-JUL-21
    23 Apr 2012
    AMENDMENT #2: 2012-APR-23

    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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