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    Clinical Trial Results:
    Efficacy and Safety of Rivaroxaban Prophylaxis Compared with Placebo in Ambulatory Cancer Subjects Initiating Systemic Cancer Therapy and at High Risk for Venous Thromboembolism

    Summary
    EudraCT number
    2015-001630-21
    Trial protocol
    GB   BE   DE   CZ   BG  
    Global end of trial date
    24 Aug 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    24 Aug 2019
    First version publication date
    24 Aug 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    39039039STM4001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02555878
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Janssen Scientific Affairs, LLC
    Sponsor organisation address
    1125 Trenton-Harbourton Road, Titusville, United States, 08560-0200
    Public contact
    Clinical Registry Group, Janssen Scientific Affairs, LLC, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group, Janssen Scientific Affairs, LLC, ClinicalTrialsEU@its.jnj.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
    24 Aug 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Aug 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary efficacy objective was to demonstrate that rivaroxaban is superior to placebo for reducing the risk of the primary composite outcome as defined by objectively confirmed symptomatic lower extremity proximal deep vein thrombosis (DVT), asymptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal pulmonary embolism (PE), incidental PE, and venous thromboembolism (VTE)-related death in ambulatory adult subjects with various cancer types receiving systemic cancer therapy who were at high risk of developing a VTE.
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices (GCP) and applicable regulatory requirements. Safety was assessed by the evaluation of bleeding event assessment and classification, clinical laboratory tests (hematology and serum chemistry), vital sign measurements, physical examinations, and adverse events.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    08 Dec 2015
    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
    Brazil: 103
    Country: Number of subjects enrolled
    Bulgaria: 34
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    Czech Republic: 37
    Country: Number of subjects enrolled
    France: 63
    Country: Number of subjects enrolled
    Belgium: 13
    Country: Number of subjects enrolled
    Germany: 113
    Country: Number of subjects enrolled
    Italy: 32
    Country: Number of subjects enrolled
    Russian Federation: 120
    Country: Number of subjects enrolled
    United Kingdom: 49
    Country: Number of subjects enrolled
    United States: 274
    Worldwide total number of subjects
    841
    EEA total number of subjects
    341
    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)
    471
    From 65 to 84 years
    363
    85 years and over
    7

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 841 subjects were enrolled in the study to receive either of the 2 treatments: rivaroxaban or matching 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
    Investigator, Carer, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Subjects received placebo tablet matched to rivaroxaban orally once daily for 180 days.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received placebo matched to rivaroxaban orally once daily.

    Arm title
    Rivaroxaban 10 mg
    Arm description
    Subjects received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.
    Arm type
    Experimental

    Investigational medicinal product name
    Rivaroxaban
    Investigational medicinal product code
    BAY-59-7939
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 10 mg of rivaroxaban tablet orally once daily.

    Number of subjects in period 1
    Placebo Rivaroxaban 10 mg
    Started
    421
    420
    Completed
    255
    270
    Not completed
    166
    150
         Death
    74
    59
         Protocol deviation
    1
    2
         Physician decision
    12
    13
         Adverse event, non-fatal
    4
    5
         Adverse event, serious fatal
    4
    1
         Adverse event, non-fatal
    4
    2
         Unspecified
    17
    17
         Consent withdrawn by subject
    48
    48
         Lost to follow-up
    2
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received placebo tablet matched to rivaroxaban orally once daily for 180 days.

    Reporting group title
    Rivaroxaban 10 mg
    Reporting group description
    Subjects received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.

    Reporting group values
    Placebo Rivaroxaban 10 mg Total
    Number of subjects
    421 420 841
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    234 237 471
        From 65 to 84 years
    182 181 363
        85 years and over
    5 2 7
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    61.9 ± 11.19 62.1 ± 11.22 -
    Title for Gender
    Units: subjects
        Female
    215 198 413
        Male
    206 222 428

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received placebo tablet matched to rivaroxaban orally once daily for 180 days.

    Reporting group title
    Rivaroxaban 10 mg
    Reporting group description
    Subjects received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.

    Primary: Percentage of Subjects with Time to First Occurrence of Primary Efficacy Endpoint (Composite and Components)

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    End point title
    Percentage of Subjects with Time to First Occurrence of Primary Efficacy Endpoint (Composite and Components)
    End point description
    Percentage of subjects with time to the first occurrence of primary efficacy endpoint (composite and components) was reported. The primary efficacy composite endpoint is time to first occurrence of objectively confirmed symptomatic and asymptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, incidental PE, or VTE-related death as adjudicated by an independent blinded Clinical Endpoint Committee (CEC). The Intent-to-treat (ITT) population consisted of all randomized subjects.
    End point type
    Primary
    End point timeframe
    Up to Day 180
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    421
    420
    Units: Percentage of Subjects
    number (not applicable)
        Primary efficacy composite endpoint
    8.79
    5.95
        Symptomatic lower extremity proximal DVT
    1.90
    2.14
        Symptomatic lower extremity distal DVT
    1.19
    0.48
        Symptomatic upper extremity DVT
    1.43
    0.95
        Symptomatic non-fatal PE
    1.19
    1.19
        Asymptomatic lower extremity proximal DVT
    2.61
    0.95
        Incidental PE
    2.38
    1.43
        VTE-related death
    0.71
    0.24
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Statistical analysis for primary efficacy composite endpoint.
    Comparison groups
    Placebo v Rivaroxaban 10 mg
    Number of subjects included in analysis
    841
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.101
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.66
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.4
         upper limit
    1.09
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Statistical analysis for Symptomatic lower extremity proximal DVT.
    Comparison groups
    Placebo v Rivaroxaban 10 mg
    Number of subjects included in analysis
    841
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.814
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.43
         upper limit
    2.91
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Statistical analysis for symptomatic lower extremity distal DVT.
    Comparison groups
    Placebo v Rivaroxaban 10 mg
    Number of subjects included in analysis
    841
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.26
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.08
         upper limit
    2.07
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Statistical analysis for symptomatic upper extremity DVT.
    Comparison groups
    Placebo v Rivaroxaban 10 mg
    Number of subjects included in analysis
    841
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.538
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.19
         upper limit
    2.39
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Statistical analysis for symptomatic non-fatal PE.
    Comparison groups
    Placebo v Rivaroxaban 10 mg
    Number of subjects included in analysis
    841
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.977
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.29
         upper limit
    3.52
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Statistical analysis for asymptomatic lower extremity proximal DVT.
    Comparison groups
    Placebo v Rivaroxaban 10 mg
    Number of subjects included in analysis
    841
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.063
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.11
         upper limit
    1.11
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Statistical analysis for incidental PE.
    Comparison groups
    Placebo v Rivaroxaban 10 mg
    Number of subjects included in analysis
    841
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.301
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.59
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.21
         upper limit
    1.62
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Statistical analysis for VTE-related death.
    Comparison groups
    Placebo v Rivaroxaban 10 mg
    Number of subjects included in analysis
    841
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.314
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.03
         upper limit
    3.18

    Primary: Percentage of Subjects with Time to the First Occurrence of Major Bleeding Events as Defined by International Society of Thrombosis and Haemostasis (ISTH)

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    End point title
    Percentage of Subjects with Time to the First Occurrence of Major Bleeding Events as Defined by International Society of Thrombosis and Haemostasis (ISTH)
    End point description
    Major bleeding is defined as clinically overt bleeding that is associated with a reduction in hemoglobin of 2 gram per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or occurrence at a critical site defined as intracranial, intra-spinal, intraocular, pericardial, intra-articular, intra-muscular with compartment syndrome, retroperitoneal, or fatal outcome. The safety analysis population consisted of all randomized subjects who received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    404
    405
    Units: Percentage of subjects
        number (not applicable)
    0.99
    1.98
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v Rivaroxaban 10 mg
    Number of subjects included in analysis
    809
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.265
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.59
         upper limit
    6.49

    Secondary: Percentage of Subjects with Time to the First Occurrence of Symptomatic VTE Events or VTE-Related Deaths

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    End point title
    Percentage of Subjects with Time to the First Occurrence of Symptomatic VTE Events or VTE-Related Deaths
    End point description
    Percentage of subjects with time to first occurrence of the composite endpoint of symptomatic VTE events (symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, or symptomatic non-fatal PE) or VTE-related deaths as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported. The ITT population consisted of all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to Day 180
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    421
    420
    Units: Percentage of subjects
        number (not applicable)
    5.23
    3.81
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Time to the First Occurrence of All-Cause Mortality

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    End point title
    Percentage of Subjects with Time to the First Occurrence of All-Cause Mortality
    End point description
    Percentage of subjects with time to the first occurrence of all-cause mortality as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported. The ITT population consisted of all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to Day 180
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    421
    420
    Units: Percentage of subjects
        number (not applicable)
    23.8
    20.0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Time to the First Occurrence of Fatal or Non-fatal Arterial Thromboembolic Events (ATE)

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    End point title
    Percentage of Subjects with Time to the First Occurrence of Fatal or Non-fatal Arterial Thromboembolic Events (ATE)
    End point description
    Percentage of subjects with time to first occurrence of fatal/non-fatal ATE (a composite of occurrence of myocardial infarction (MI), stroke [ischemic infarction with or without hemorrhagic conversion or primary hemorrhagic events – intraparenchymal hemorrhage, subdural hematoma or epidural hematoma] or any other ATE recorded) event as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported. The ITT population consisted of all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to Day 180
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    421
    420
    Units: Percentage of subjects
        number (not applicable)
    1.66
    0.95
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Time to the First Occurrence of Fatal or Non-fatal Visceral VTE

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    End point title
    Percentage of Subjects with Time to the First Occurrence of Fatal or Non-fatal Visceral VTE
    End point description
    Percentage of subjects with time to the first occurrence of fatal or non-fatal visceral VTE as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported. The ITT population consisted of all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to Day 180
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    421
    420
    Units: Percentage of subjects
        number (not applicable)
    0.48
    0.24
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Time to the First Occurrence of Composite Efficacy Endpoint 1

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    End point title
    Percentage of Subjects with Time to the First Occurrence of Composite Efficacy Endpoint 1
    End point description
    Percentage of subjects with time to first occurrence of composite efficacy endpoint 1 (composite of objectively confirmed symptomatic and asymptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, incidental PE or all-cause mortality) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported. The ITT population consisted of all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to Day 180
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    421
    420
    Units: Percentage of subjects
        number (not applicable)
    29.5
    23.1
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Time to First Occurrence of Composite Efficacy Endpoint 2

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    End point title
    Percentage of Subjects with Time to First Occurrence of Composite Efficacy Endpoint 2
    End point description
    Percentage of subjects with time to first occurrence of composite efficacy endpoint 2 (composite of objectively confirmed symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE or VTE-related deaths) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported. The ITT population consisted of all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to Day 180
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    421
    420
    Units: Percentage of subjects
        number (not applicable)
    5.23
    3.81
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Time to First Occurrence of Composite Efficacy Endpoint 3

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    End point title
    Percentage of Subjects with Time to First Occurrence of Composite Efficacy Endpoint 3
    End point description
    Percentage of subjects with time to first occurrence of composite efficacy endpoint 3 (composite of objectively confirmed symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, asymptomatic lower extremity proximal DVT, symptomatic non-fatal PE, incidental PE, VTE-related deaths, fatal/non-fatal ATE [MI, stroke {ischemic infarction with or without hemorrhagic conversion or primary hemorrhagic events – intraparenchymal hemorrhage, subdural hematoma or epidural hematoma} or any ATE] or fatal/non-fatal visceral VTE) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported. The ITT population consisted of all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to Day 180
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    421
    420
    Units: Percentage of subjects
        number (not applicable)
    10.7
    6.90
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Time to First Occurrence of Composite Efficacy Endpoint 4

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    End point title
    Percentage of Subjects with Time to First Occurrence of Composite Efficacy Endpoint 4
    End point description
    Percentage of subjects with time to first occurrence of composite efficacy endpoint 4 (composite of objectively confirmed symptomatic lower extremity proximal DVT, symptomatic lower extremity distal DVT, symptomatic upper extremity DVT, symptomatic non-fatal PE, VTE-related deaths or major bleeding events up to day 180) as adjudicated by an independent blinded CEC up-to-Day 180 observation period was reported. The ITT population consisted of all randomized subjects.
    End point type
    Secondary
    End point timeframe
    Up to Day 180
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    421
    420
    Units: Percentage of subjects
        number (not applicable)
    6.89
    5.71
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Time to the First Occurrence of Clinically Relevant Non-major Bleeding

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    End point title
    Percentage of Subjects with Time to the First Occurrence of Clinically Relevant Non-major Bleeding
    End point description
    Percentage of subjects with time time to the first occurrence of clinically relevant non-major bleeding was reported. Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, or unscheduled contact with a physician, or temporary cessation of study treatment, or discomfort such as pain, or impairment of activities of daily life. The safety analysis population consisted of all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    404
    405
    Units: Percentage of subjects
        number (not applicable)
    1.98
    2.72
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Time to the First Occurrence of Minor bleeding

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    End point title
    Percentage of Subjects with Time to the First Occurrence of Minor bleeding
    End point description
    Percentage of subjects with time to the first occurrence of minor bleeding was reported. Minor bleeding (that is, minimal bleeding) is defined as overt bleeding episodes not meeting the criteria for major or clinically relevant non-major bleeding event. The safety analysis population consisted of all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    404
    405
    Units: Percentage of subjects
        number (not applicable)
    3.96
    6.91
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with Time to the First Occurrence of Any Bleeding

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    End point title
    Percentage of Subjects with Time to the First Occurrence of Any Bleeding
    End point description
    Percentage of subjects with time to the first occurrence of any bleeding event was reported. Any bleeding is defined as a composite of major bleeding, clinically relevant non-major bleeding, or minor bleeding. The safety analysis population consisted of all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug to 2 days after the last dose of the study drug (up to 32 weeks)
    End point values
    Placebo Rivaroxaban 10 mg
    Number of subjects analysed
    404
    405
    Units: Percentage of subjects
        number (not applicable)
    6.44
    11.1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 32 weeks
    Adverse event reporting additional description
    The safety analysis population consisted of all randomized subjects who received at least 1 dose of study drug.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Rivaroxaban 10 mg
    Reporting group description
    Subjects received rivaroxaban 10 milligram (mg) tablet orally once daily for 180 days.

    Reporting group title
    Placebo
    Reporting group description
    Subjects received placebo tablet matched to rivaroxaban orally once daily for 180 days.

    Serious adverse events
    Rivaroxaban 10 mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    134 / 405 (33.09%)
    128 / 404 (31.68%)
         number of deaths (all causes)
    85
    106
         number of deaths resulting from adverse events
    Vascular disorders
    Superior Vena Cava Syndrome
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer Pain
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung Adenocarcinoma
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to Liver
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metastases to Central Nervous System
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant Neoplasm Progression
         subjects affected / exposed
    29 / 405 (7.16%)
    33 / 404 (8.17%)
         occurrences causally related to treatment / all
    0 / 29
    0 / 33
         deaths causally related to treatment / all
    0 / 28
    0 / 29
    Neoplasm Progression
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metastases to Lymph Nodes
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian Cancer
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour Associated Fever
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug Hypersensitivity
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest Pain
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Condition Aggravated
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease Progression
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    General Physical Health Deterioration
         subjects affected / exposed
    5 / 405 (1.23%)
    4 / 404 (0.99%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Fatigue
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised Oedema
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal Inflammation
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple Organ Dysfunction Syndrome
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    8 / 405 (1.98%)
    8 / 404 (1.98%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional State
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Female Genital Tract Fistula
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Hip Fracture
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pubis Fracture
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Glomerular Filtration Rate Decreased
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General Physical Condition Abnormal
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood Bilirubin Increased
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration Bronchial
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Platelet Count Decreased
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial Fibrillation
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular Tachycardia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial Effusion
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary Artery Disease
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiotoxicity
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    3 / 405 (0.74%)
    5 / 404 (1.24%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Acute Respiratory Failure
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngospasm
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural Effusion
         subjects affected / exposed
    3 / 405 (0.74%)
    3 / 404 (0.74%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Distress
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Failure
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 405 (0.74%)
    3 / 404 (0.74%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 405 (0.25%)
    3 / 404 (0.74%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile Neutropenia
         subjects affected / exposed
    6 / 405 (1.48%)
    4 / 404 (0.99%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (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
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient Global Amnesia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle Contractions Involuntary
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal Pain
         subjects affected / exposed
    5 / 405 (1.23%)
    3 / 404 (0.74%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Constipation
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (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 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 405 (0.49%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal Obstruction
         subjects affected / exposed
    3 / 405 (0.74%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 405 (0.25%)
    4 / 404 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastrointestinal Disorder
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal Perforation
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Intestinal Infarction
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal Toxicity
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal Obstruction
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nausea
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal Obstruction
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Intestinal Ischaemia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 405 (0.49%)
    3 / 404 (0.74%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small Intestinal Obstruction
         subjects affected / exposed
    3 / 405 (0.74%)
    3 / 404 (0.74%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute Kidney Injury
         subjects affected / exposed
    3 / 405 (0.74%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal Failure
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile Duct Obstruction
         subjects affected / exposed
    1 / 405 (0.25%)
    3 / 404 (0.74%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Jaundice
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Decubitus Ulcer
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug Eruption
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash Macular
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         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 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal Pain
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle Tightness
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular Weakness
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological Fracture
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Inappropriate Antidiuretic Hormone Secretion
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    3 / 405 (0.74%)
    5 / 404 (1.24%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased Appetite
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic Ketoacidosis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrolyte Imbalance
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to Thrive
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Feeding Intolerance
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal Sepsis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess Limb
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal Abscess
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atypical Pneumonia
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary Sepsis
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    3 / 405 (0.74%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis Infective
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium Difficile Colitis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device Related Infection
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile Infection
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella Sepsis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower Respiratory Tract Infection
         subjects affected / exposed
    0 / 405 (0.00%)
    3 / 404 (0.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis Viral
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic Sepsis
         subjects affected / exposed
    0 / 405 (0.00%)
    3 / 404 (0.74%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung Infection
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Oral Candidiasis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia Bacterial
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Tract Infection
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    6 / 405 (1.48%)
    4 / 404 (0.99%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Pneumonia
         subjects affected / exposed
    10 / 405 (2.47%)
    4 / 404 (0.99%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic Shock
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Urinary Tract Infection
         subjects affected / exposed
    3 / 405 (0.74%)
    2 / 404 (0.50%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Rivaroxaban 10 mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    221 / 405 (54.57%)
    225 / 404 (55.69%)
    Vascular disorders
    Hyperaemia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Haematoma
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Flushing
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Hot Flush
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Hypotension
         subjects affected / exposed
    3 / 405 (0.74%)
    6 / 404 (1.49%)
         occurrences all number
    3
    6
    Pallor
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Peripheral Coldness
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Peripheral Vascular Disorder
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Hypertension
         subjects affected / exposed
    6 / 405 (1.48%)
    8 / 404 (1.98%)
         occurrences all number
    7
    9
    Phlebitis
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    4
    1
    Varicose Vein
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Phlebitis Superficial
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Surgical and medical procedures
    Thrombosis Prophylaxis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Tooth Extraction
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant Neoplasm Progression
         subjects affected / exposed
    7 / 405 (1.73%)
    4 / 404 (0.99%)
         occurrences all number
    7
    5
    Brain Cancer Metastatic
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Cancer Pain
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    2
    Metastases to Central Nervous System
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Testicular Neoplasm
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Tumour Pain
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Immune system disorders
    Food Allergy
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Drug Hypersensitivity
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Seasonal Allergy
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Chest Pain
         subjects affected / exposed
    4 / 405 (0.99%)
    1 / 404 (0.25%)
         occurrences all number
    4
    1
    Asthenia
         subjects affected / exposed
    16 / 405 (3.95%)
    19 / 404 (4.70%)
         occurrences all number
    18
    38
    Extravasation
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Chills
         subjects affected / exposed
    2 / 405 (0.49%)
    2 / 404 (0.50%)
         occurrences all number
    2
    2
    Gait Disturbance
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Fatigue
         subjects affected / exposed
    44 / 405 (10.86%)
    32 / 404 (7.92%)
         occurrences all number
    55
    41
    Feeling Cold
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Induration
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    General Physical Health Deterioration
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Inflammation
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Influenza Like Illness
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Localised Oedema
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Mucosal Dryness
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Malaise
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    2
    Mucosal Inflammation
         subjects affected / exposed
    8 / 405 (1.98%)
    5 / 404 (1.24%)
         occurrences all number
    10
    5
    Non-Cardiac Chest Pain
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Oedema
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Oedema Peripheral
         subjects affected / exposed
    9 / 405 (2.22%)
    19 / 404 (4.70%)
         occurrences all number
    10
    23
    Pain
         subjects affected / exposed
    6 / 405 (1.48%)
    7 / 404 (1.73%)
         occurrences all number
    6
    8
    Peripheral Swelling
         subjects affected / exposed
    0 / 405 (0.00%)
    4 / 404 (0.99%)
         occurrences all number
    0
    5
    Performance Status Decreased
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    9 / 405 (2.22%)
    16 / 404 (3.96%)
         occurrences all number
    12
    19
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    4 / 405 (0.99%)
    3 / 404 (0.74%)
         occurrences all number
    4
    3
    Confusional State
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Irritability
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Mood Swings
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Insomnia
         subjects affected / exposed
    8 / 405 (1.98%)
    5 / 404 (1.24%)
         occurrences all number
    8
    5
    Depression
         subjects affected / exposed
    2 / 405 (0.49%)
    4 / 404 (0.99%)
         occurrences all number
    2
    4
    Sleep Disorder
         subjects affected / exposed
    2 / 405 (0.49%)
    4 / 404 (0.99%)
         occurrences all number
    2
    4
    Stress
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Restlessness
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Reproductive system and breast disorders
    Genital Pain
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Prostatitis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Vaginal Discharge
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Pelvic Pain
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Face Injury
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Fall
         subjects affected / exposed
    2 / 405 (0.49%)
    3 / 404 (0.74%)
         occurrences all number
    2
    3
    Contusion
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Limb Injury
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Head Injury
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Procedural Headache
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Lumbar Vertebral Fracture
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Radiation Injury
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Radiation Skin Injury
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    2
    Scar
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Scratch
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Thermal Burn
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    2
    Tooth Fracture
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    9 / 405 (2.22%)
    10 / 404 (2.48%)
         occurrences all number
    14
    12
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    6 / 405 (1.48%)
    12 / 404 (2.97%)
         occurrences all number
    11
    15
    Bilirubin Conjugated Decreased
         subjects affected / exposed
    4 / 405 (0.99%)
    10 / 404 (2.48%)
         occurrences all number
    4
    10
    Blood Albumin Decreased
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Blood Alkaline Phosphatase Increased
         subjects affected / exposed
    6 / 405 (1.48%)
    6 / 404 (1.49%)
         occurrences all number
    6
    6
    Blood Alkaline Phosphatase Decreased
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Blood Bilirubin Decreased
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Blood Bicarbonate Increased
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Blood Calcium Increased
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Blood Calcium Decreased
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Blood Bilirubin Increased
         subjects affected / exposed
    1 / 405 (0.25%)
    6 / 404 (1.49%)
         occurrences all number
    1
    7
    Blood Creatinine Decreased
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Blood Chloride Decreased
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Blood Creatinine Increased
         subjects affected / exposed
    3 / 405 (0.74%)
    2 / 404 (0.50%)
         occurrences all number
    3
    2
    Blood Glucose Decreased
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Blood Glucose Increased
         subjects affected / exposed
    5 / 405 (1.23%)
    12 / 404 (2.97%)
         occurrences all number
    5
    14
    Blood Potassium Decreased
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences all number
    2
    1
    Blood Potassium Increased
         subjects affected / exposed
    2 / 405 (0.49%)
    6 / 404 (1.49%)
         occurrences all number
    2
    6
    Blood Sodium Decreased
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Blood Urea Increased
         subjects affected / exposed
    0 / 405 (0.00%)
    4 / 404 (0.99%)
         occurrences all number
    0
    4
    Blood Sodium Increased
         subjects affected / exposed
    0 / 405 (0.00%)
    3 / 404 (0.74%)
         occurrences all number
    0
    3
    Blood Uric Acid Increased
         subjects affected / exposed
    3 / 405 (0.74%)
    1 / 404 (0.25%)
         occurrences all number
    3
    2
    C-Reactive Protein Increased
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Creatinine Renal Clearance Decreased
         subjects affected / exposed
    3 / 405 (0.74%)
    8 / 404 (1.98%)
         occurrences all number
    4
    8
    Creatinine Renal Clearance Increased
         subjects affected / exposed
    4 / 405 (0.99%)
    4 / 404 (0.99%)
         occurrences all number
    4
    5
    Gamma-Glutamyltransferase Increased
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences all number
    2
    1
    Haematocrit Decreased
         subjects affected / exposed
    5 / 405 (1.23%)
    0 / 404 (0.00%)
         occurrences all number
    5
    0
    Hepatic Enzyme Increased
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Haemoglobin Decreased
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Lymphocyte Count Decreased
         subjects affected / exposed
    5 / 405 (1.23%)
    7 / 404 (1.73%)
         occurrences all number
    7
    9
    Lymphocyte Count Increased
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    2
    Monocyte Count Decreased
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Monocyte Count Increased
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    2
    Neutrophil Count Decreased
         subjects affected / exposed
    4 / 405 (0.99%)
    10 / 404 (2.48%)
         occurrences all number
    6
    11
    Neutrophil Count Increased
         subjects affected / exposed
    2 / 405 (0.49%)
    2 / 404 (0.50%)
         occurrences all number
    2
    2
    Platelet Count Decreased
         subjects affected / exposed
    4 / 405 (0.99%)
    10 / 404 (2.48%)
         occurrences all number
    4
    17
    Platelet Count Increased
         subjects affected / exposed
    6 / 405 (1.48%)
    4 / 404 (0.99%)
         occurrences all number
    6
    4
    Protein Total Decreased
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Red Blood Cell Count Decreased
         subjects affected / exposed
    7 / 405 (1.73%)
    5 / 404 (1.24%)
         occurrences all number
    7
    5
    Transaminases Increased
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences all number
    2
    3
    Vascular Resistance Systemic Increased
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Vitamin B12 Decreased
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Troponin Increased
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Weight Increased
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Weight Decreased
         subjects affected / exposed
    10 / 405 (2.47%)
    9 / 404 (2.23%)
         occurrences all number
    10
    10
    White Blood Cell Count Increased
         subjects affected / exposed
    3 / 405 (0.74%)
    4 / 404 (0.99%)
         occurrences all number
    3
    4
    White Blood Cell Count Decreased
         subjects affected / exposed
    6 / 405 (1.48%)
    9 / 404 (2.23%)
         occurrences all number
    8
    10
    Cardiac disorders
    Angina Pectoris
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences all number
    2
    1
    Arrhythmia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Atrial Fibrillation
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Bradycardia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Left Ventricular Hypertrophy
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Cardiovascular Disorder
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Cardiac Failure Congestive
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Myocardial Ischaemia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Palpitations
         subjects affected / exposed
    0 / 405 (0.00%)
    3 / 404 (0.74%)
         occurrences all number
    0
    3
    Supraventricular Extrasystoles
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Tachycardia
         subjects affected / exposed
    2 / 405 (0.49%)
    3 / 404 (0.74%)
         occurrences all number
    2
    3
    Sinus Tachycardia
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Bronchopneumopathy
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Cough
         subjects affected / exposed
    9 / 405 (2.22%)
    14 / 404 (3.47%)
         occurrences all number
    9
    17
    Chylothorax
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    2
    Dyspnoea
         subjects affected / exposed
    17 / 405 (4.20%)
    9 / 404 (2.23%)
         occurrences all number
    19
    11
    Dyspnoea Exertional
         subjects affected / exposed
    0 / 405 (0.00%)
    4 / 404 (0.99%)
         occurrences all number
    0
    4
    Dysaesthesia Pharynx
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Dysphonia
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Epistaxis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Mediastinal Shift
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Lung Disorder
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Hypoxia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Hiccups
         subjects affected / exposed
    2 / 405 (0.49%)
    2 / 404 (0.50%)
         occurrences all number
    2
    2
    Nasal Dryness
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Oropharyngeal Pain
         subjects affected / exposed
    4 / 405 (0.99%)
    3 / 404 (0.74%)
         occurrences all number
    4
    3
    Pleural Effusion
         subjects affected / exposed
    2 / 405 (0.49%)
    3 / 404 (0.74%)
         occurrences all number
    3
    3
    Pleural Thickening
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Nasal Congestion
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Productive Cough
         subjects affected / exposed
    0 / 405 (0.00%)
    7 / 404 (1.73%)
         occurrences all number
    0
    7
    Respiratory Disorder
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Respiratory Tract Congestion
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Rhinitis Allergic
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Sinus Congestion
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Upper-Airway Cough Syndrome
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Wheezing
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences all number
    2
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    46 / 405 (11.36%)
    59 / 404 (14.60%)
         occurrences all number
    56
    75
    Anaemia Macrocytic
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Haemorrhagic Diathesis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Febrile Bone Marrow Aplasia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Hypocoagulable State
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Hypochromic Anaemia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Increased Tendency to Bruise
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Leukocytosis
         subjects affected / exposed
    2 / 405 (0.49%)
    2 / 404 (0.50%)
         occurrences all number
    3
    2
    Iron Deficiency Anaemia
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences all number
    4
    1
    Leukopenia
         subjects affected / exposed
    7 / 405 (1.73%)
    11 / 404 (2.72%)
         occurrences all number
    11
    22
    Lymphadenopathy
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Pancytopenia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Lymphopenia
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Neutropenia
         subjects affected / exposed
    25 / 405 (6.17%)
    24 / 404 (5.94%)
         occurrences all number
    33
    43
    Splenic Infarction
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    12 / 405 (2.96%)
    19 / 404 (4.70%)
         occurrences all number
    14
    30
    Thrombocytosis
         subjects affected / exposed
    1 / 405 (0.25%)
    6 / 404 (1.49%)
         occurrences all number
    1
    6
    Nervous system disorders
    Anosmia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Ageusia
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Ataxia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Balance Disorder
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Coordination Abnormal
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Depressed Level of Consciousness
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Dizziness
         subjects affected / exposed
    2 / 405 (0.49%)
    4 / 404 (0.99%)
         occurrences all number
    2
    4
    Dysaesthesia
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    2
    1
    Encephalopathy
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Dysgeusia
         subjects affected / exposed
    5 / 405 (1.23%)
    3 / 404 (0.74%)
         occurrences all number
    6
    3
    Headache
         subjects affected / exposed
    5 / 405 (1.23%)
    6 / 404 (1.49%)
         occurrences all number
    5
    6
    Hypoaesthesia
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    3
    Hypotonia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Memory Impairment
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Epilepsy
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Neuralgia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Neuropathy Peripheral
         subjects affected / exposed
    16 / 405 (3.95%)
    12 / 404 (2.97%)
         occurrences all number
    17
    12
    Orthostatic Intolerance
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    2
    Migraine
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    2
    Peripheral Motor Neuropathy
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Peripheral Sensory Neuropathy
         subjects affected / exposed
    8 / 405 (1.98%)
    5 / 404 (1.24%)
         occurrences all number
    8
    8
    Polyneuropathy
         subjects affected / exposed
    7 / 405 (1.73%)
    8 / 404 (1.98%)
         occurrences all number
    9
    8
    Paraesthesia
         subjects affected / exposed
    4 / 405 (0.99%)
    18 / 404 (4.46%)
         occurrences all number
    4
    22
    Sciatica
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Psychomotor Hyperactivity
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Thermohyperaesthesia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Sinus Headache
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Seizure
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Tremor
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Eye disorders
    Blepharospasm
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Eye Discharge
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Dry Eye
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Eye Irritation
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Eye Pain
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Lacrimation Increased
         subjects affected / exposed
    3 / 405 (0.74%)
    0 / 404 (0.00%)
         occurrences all number
    3
    0
    Photopsia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Vision Blurred
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    2
    Visual Impairment
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Hypoacusis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Deafness
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Tinnitus
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Vertigo
         subjects affected / exposed
    2 / 405 (0.49%)
    3 / 404 (0.74%)
         occurrences all number
    2
    3
    Gastrointestinal disorders
    Abdominal Discomfort
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Abdominal Distension
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences all number
    2
    1
    Abdominal Pain Lower
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Abdominal Pain
         subjects affected / exposed
    14 / 405 (3.46%)
    14 / 404 (3.47%)
         occurrences all number
    14
    15
    Abdominal Pain Upper
         subjects affected / exposed
    7 / 405 (1.73%)
    6 / 404 (1.49%)
         occurrences all number
    8
    8
    Abdominal Rigidity
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Anal Incontinence
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    2
    Aphthous Ulcer
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Ascites
         subjects affected / exposed
    1 / 405 (0.25%)
    4 / 404 (0.99%)
         occurrences all number
    1
    4
    Cheilitis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    29 / 405 (7.16%)
    12 / 404 (2.97%)
         occurrences all number
    30
    12
    Dental Pulp Disorder
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    34 / 405 (8.40%)
    36 / 404 (8.91%)
         occurrences all number
    40
    44
    Dry Mouth
         subjects affected / exposed
    4 / 405 (0.99%)
    2 / 404 (0.50%)
         occurrences all number
    4
    2
    Dyspepsia
         subjects affected / exposed
    8 / 405 (1.98%)
    5 / 404 (1.24%)
         occurrences all number
    9
    5
    Flatulence
         subjects affected / exposed
    2 / 405 (0.49%)
    3 / 404 (0.74%)
         occurrences all number
    2
    3
    Dysphagia
         subjects affected / exposed
    3 / 405 (0.74%)
    2 / 404 (0.50%)
         occurrences all number
    3
    2
    Gastritis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    5 / 405 (1.23%)
    2 / 404 (0.50%)
         occurrences all number
    5
    2
    Gastrointestinal Pain
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Nausea
         subjects affected / exposed
    55 / 405 (13.58%)
    55 / 404 (13.61%)
         occurrences all number
    78
    63
    Oesophageal Compression
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Oesophageal Spasm
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Oesophagitis
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    3
    Proctalgia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Oral Pain
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Pancreatic Failure
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Stomatitis
         subjects affected / exposed
    8 / 405 (1.98%)
    7 / 404 (1.73%)
         occurrences all number
    8
    8
    Rectal Prolapse
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Tongue Coated
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Vomiting
         subjects affected / exposed
    28 / 405 (6.91%)
    17 / 404 (4.21%)
         occurrences all number
    32
    18
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    0 / 405 (0.00%)
    4 / 404 (0.99%)
         occurrences all number
    0
    4
    Bladder Spasm
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Hypertonic Bladder
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Dysuria
         subjects affected / exposed
    0 / 405 (0.00%)
    5 / 404 (1.24%)
         occurrences all number
    0
    5
    Kidney Congestion
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Nephrolithiasis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Renal Failure
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Pollakiuria
         subjects affected / exposed
    3 / 405 (0.74%)
    2 / 404 (0.50%)
         occurrences all number
    3
    2
    Nephropathy Toxic
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Renal Cyst
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Renal Infarct
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Urinary Incontinence
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    2
    Urinary Tract Pain
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Urinary Retention
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Cholestasis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Hepatitis Toxic
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Hepatic Steatosis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Hepatotoxicity
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Hepatocellular Injury
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Liver Injury
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Jaundice
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Dermatitis Acneiform
         subjects affected / exposed
    1 / 405 (0.25%)
    3 / 404 (0.74%)
         occurrences all number
    1
    3
    Decubitus Ulcer
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Butterfly Rash
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Blister
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Alopecia
         subjects affected / exposed
    14 / 405 (3.46%)
    12 / 404 (2.97%)
         occurrences all number
    14
    12
    Ecchymosis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Dermatitis Exfoliative Generalised
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Dry Skin
         subjects affected / exposed
    4 / 405 (0.99%)
    0 / 404 (0.00%)
         occurrences all number
    4
    0
    Dermatitis Allergic
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Nail Disorder
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Nail Discolouration
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Lividity
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Erythema
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Hyperhidrosis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Palmar-Plantar Erythrodysaesthesia Syndrome
         subjects affected / exposed
    10 / 405 (2.47%)
    9 / 404 (2.23%)
         occurrences all number
    10
    9
    Pain of Skin
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Night Sweats
         subjects affected / exposed
    2 / 405 (0.49%)
    5 / 404 (1.24%)
         occurrences all number
    2
    6
    Nail Dystrophy
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Pruritus
         subjects affected / exposed
    4 / 405 (0.99%)
    3 / 404 (0.74%)
         occurrences all number
    4
    3
    Rash
         subjects affected / exposed
    5 / 405 (1.23%)
    7 / 404 (1.73%)
         occurrences all number
    5
    7
    Rash Generalised
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Rash Maculo-Papular
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Photosensitivity Reaction
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Skin Irritation
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Rash Pruritic
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Seborrhoea
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Skin Exfoliation
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Solar Dermatitis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Skin Mass
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Skin Reaction
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Skin Lesion
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    2
    Yellow Skin
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Product issues
    Thrombosis in Device
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    10 / 405 (2.47%)
    1 / 404 (0.25%)
         occurrences all number
    12
    1
    Bone Pain
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Back Pain
         subjects affected / exposed
    5 / 405 (1.23%)
    6 / 404 (1.49%)
         occurrences all number
    5
    6
    Hypercreatinaemia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Flank Pain
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Joint Swelling
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Muscle Mass
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Muscle Spasms
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Muscle Tightness
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Muscular Weakness
         subjects affected / exposed
    2 / 405 (0.49%)
    5 / 404 (1.24%)
         occurrences all number
    2
    7
    Musculoskeletal Pain
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Myalgia
         subjects affected / exposed
    3 / 405 (0.74%)
    2 / 404 (0.50%)
         occurrences all number
    3
    2
    Musculoskeletal Chest Pain
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    2
    Osteoarthritis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Pain in Extremity
         subjects affected / exposed
    6 / 405 (1.48%)
    8 / 404 (1.98%)
         occurrences all number
    6
    9
    Pain in Jaw
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Spinal Pain
         subjects affected / exposed
    2 / 405 (0.49%)
    2 / 404 (0.50%)
         occurrences all number
    2
    2
    Endocrine disorders
    Hypercalcaemia of Malignancy
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Hypothyroidism
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Abnormal Loss of Weight
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Decreased Appetite
         subjects affected / exposed
    21 / 405 (5.19%)
    25 / 404 (6.19%)
         occurrences all number
    23
    30
    Dehydration
         subjects affected / exposed
    9 / 405 (2.22%)
    7 / 404 (1.73%)
         occurrences all number
    10
    8
    Diabetes Mellitus
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Electrolyte Depletion
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Folate Deficiency
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences all number
    2
    1
    Fluid Retention
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Hypercalcaemia
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    3
    0
    Gout
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Hyperglycaemia
         subjects affected / exposed
    5 / 405 (1.23%)
    1 / 404 (0.25%)
         occurrences all number
    6
    1
    Hyperlipidaemia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Hyperuricaemia
         subjects affected / exposed
    2 / 405 (0.49%)
    2 / 404 (0.50%)
         occurrences all number
    2
    2
    Hypocalcaemia
         subjects affected / exposed
    6 / 405 (1.48%)
    2 / 404 (0.50%)
         occurrences all number
    7
    2
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Hypokalaemia
         subjects affected / exposed
    18 / 405 (4.44%)
    10 / 404 (2.48%)
         occurrences all number
    21
    11
    Hypomagnesaemia
         subjects affected / exposed
    11 / 405 (2.72%)
    4 / 404 (0.99%)
         occurrences all number
    11
    4
    Hypoglycaemia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Hypophosphataemia
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Hyponatraemia
         subjects affected / exposed
    4 / 405 (0.99%)
    3 / 404 (0.74%)
         occurrences all number
    4
    3
    Iron Deficiency
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Lactic Acidosis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Hypovolaemia
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Malnutrition
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Metabolic Acidosis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Protein Deficiency
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Type 2 Diabetes Mellitus
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Vitamin B12 Deficiency
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Vitamin D Deficiency
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences all number
    2
    1
    Infections and infestations
    Abscess
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Abscess Limb
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Angular Cheilitis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Biliary Sepsis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Bronchitis
         subjects affected / exposed
    1 / 405 (0.25%)
    5 / 404 (1.24%)
         occurrences all number
    1
    6
    Candida Infection
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Clostridium Difficile Colitis
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Catheter Site Infection
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Cellulitis
         subjects affected / exposed
    2 / 405 (0.49%)
    2 / 404 (0.50%)
         occurrences all number
    3
    2
    Clostridium Difficile Infection
         subjects affected / exposed
    1 / 405 (0.25%)
    1 / 404 (0.25%)
         occurrences all number
    1
    1
    Coccidioidomycosis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    3 / 405 (0.74%)
    0 / 404 (0.00%)
         occurrences all number
    3
    0
    Ear Infection
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Device Related Infection
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Folliculitis
         subjects affected / exposed
    4 / 405 (0.99%)
    0 / 404 (0.00%)
         occurrences all number
    4
    0
    Fungal Infection
         subjects affected / exposed
    0 / 405 (0.00%)
    2 / 404 (0.50%)
         occurrences all number
    0
    3
    Fungal Skin Infection
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Furuncle
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis Viral
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Influenza
         subjects affected / exposed
    2 / 405 (0.49%)
    1 / 404 (0.25%)
         occurrences all number
    2
    1
    Genital Infection Fungal
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    3 / 405 (0.74%)
    2 / 404 (0.50%)
         occurrences all number
    3
    2
    Oesophageal Candidiasis
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Oral Candidiasis
         subjects affected / exposed
    2 / 405 (0.49%)
    0 / 404 (0.00%)
         occurrences all number
    2
    0
    Oral Fungal Infection
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Oral Herpes
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Oral Infection
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Perirectal Abscess
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Pharyngitis Streptococcal
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Paronychia
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Pneumonia
         subjects affected / exposed
    1 / 405 (0.25%)
    3 / 404 (0.74%)
         occurrences all number
    1
    3
    Pneumonia Bacterial
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Pulpitis Dental
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Pyelonephritis Chronic
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Postoperative Wound Infection
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Respiratory Tract Infection
         subjects affected / exposed
    3 / 405 (0.74%)
    0 / 404 (0.00%)
         occurrences all number
    3
    0
    Rhinitis
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Rhinovirus Infection
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Sepsis
         subjects affected / exposed
    1 / 405 (0.25%)
    2 / 404 (0.50%)
         occurrences all number
    1
    2
    Septic Shock
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0
    Spinal Cord Infection
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Sinusitis
         subjects affected / exposed
    1 / 405 (0.25%)
    4 / 404 (0.99%)
         occurrences all number
    1
    4
    Tooth Infection
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Upper Respiratory Tract Infection
         subjects affected / exposed
    4 / 405 (0.99%)
    4 / 404 (0.99%)
         occurrences all number
    4
    4
    Urinary Tract Infection
         subjects affected / exposed
    6 / 405 (1.48%)
    6 / 404 (1.49%)
         occurrences all number
    6
    9
    Urinary Tract Infection Bacterial
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Viral Infection
         subjects affected / exposed
    0 / 405 (0.00%)
    1 / 404 (0.25%)
         occurrences all number
    0
    1
    Vulvovaginal Mycotic Infection
         subjects affected / exposed
    1 / 405 (0.25%)
    0 / 404 (0.00%)
         occurrences all number
    1
    0

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Feb 2018
    This amendment included an increase in the planned enrollment to approximately 800 subjects to account for the high subject discontinuation rate, the addition of symptomatic lower extremity distal DVT to the primary efficacy composite endpoint and secondary efficacy composite endpoint, clarifications to the statistical analysis methods, corrections to the efficacy evaluations, outcomes, and endpoints (that is, symptomatic proximal upper extremity DVT was corrected to symptomatic upper extremity DVT and non-fatal PE was corrected to symptomatic non-fatal PE), and minor editorial changes.

    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
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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