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    Clinical Trial Results:
    A Randomized, Open-Label, Phase 3 Study of Abemaciclib Combined with Standard Adjuvant Endocrine Therapy versus Standard Adjuvant Endocrine Therapy Alone in Patients with High Risk, Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer

    Summary
    EudraCT number
    		 2016-004362-26
    Trial protocol
    		 DE   NL   HU   GB   BE   DK   FI   PL   GR   AT   ES   CZ   FR   PT   IT   RO  
    Global end of trial date

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Mar 2021
    First version publication date
    31 Mar 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    I3Y-MC-JPCF
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03155997
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 16338
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    16 Mar 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Mar 2020
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, hormone receptor positive (HR+), human epidermal receptor 2 negative (HER2-), breast cancer.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    12 Jul 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 145
    Country: Number of subjects enrolled
    Australia: 217
    Country: Number of subjects enrolled
    Austria: 42
    Country: Number of subjects enrolled
    Belgium: 116
    Country: Number of subjects enrolled
    Brazil: 297
    Country: Number of subjects enrolled
    Canada: 44
    Country: Number of subjects enrolled
    China: 357
    Country: Number of subjects enrolled
    Czechia: 27
    Country: Number of subjects enrolled
    Denmark: 112
    Country: Number of subjects enrolled
    Finland: 94
    Country: Number of subjects enrolled
    France: 187
    Country: Number of subjects enrolled
    Germany: 300
    Country: Number of subjects enrolled
    Greece: 138
    Country: Number of subjects enrolled
    Hong Kong: 20
    Country: Number of subjects enrolled
    Hungary: 52
    Country: Number of subjects enrolled
    India: 112
    Country: Number of subjects enrolled
    Israel: 77
    Country: Number of subjects enrolled
    Italy: 131
    Country: Number of subjects enrolled
    Japan: 377
    Country: Number of subjects enrolled
    Mexico: 225
    Country: Number of subjects enrolled
    Netherlands: 19
    Country: Number of subjects enrolled
    New Zealand: 43
    Country: Number of subjects enrolled
    Poland: 125
    Country: Number of subjects enrolled
    Portugal: 37
    Country: Number of subjects enrolled
    Puerto Rico: 4
    Country: Number of subjects enrolled
    Romania: 113
    Country: Number of subjects enrolled
    Russian Federation: 139
    Country: Number of subjects enrolled
    Saudi Arabia: 14
    Country: Number of subjects enrolled
    Singapore: 32
    Country: Number of subjects enrolled
    South Africa: 9
    Country: Number of subjects enrolled
    Korea, Republic of: 245
    Country: Number of subjects enrolled
    Spain: 292
    Country: Number of subjects enrolled
    Sweden: 12
    Country: Number of subjects enrolled
    Taiwan: 124
    Country: Number of subjects enrolled
    Turkey: 235
    Country: Number of subjects enrolled
    Ukraine: 105
    Country: Number of subjects enrolled
    United Kingdom: 199
    Country: Number of subjects enrolled
    United States: 820
    Worldwide total number of subjects
    5637
    EEA total number of subjects
    1797
    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)
    4787
    From 65 to 84 years
    850
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Completers included participants who had recurrence disease, death due to any cause, and participants off treatment but on study follow-up.

    Pre-assignment
    Screening details
    		 No Text Available

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 150 mg Abemaciclib + Endocrine Therapy
    Arm description
    		 Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians’ choice) standard-of-care was administered according to package label until discontinuation criteria were met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    Other name
    LY2835219
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first.

    Investigational medicinal product name
    Standard Adjuvant Endocrine Therapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Oral liquid, Tablet
    Routes of administration
    Intramuscular use, Oral use, Subcutaneous use
    Dosage and administration details
    Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.

    Arm title
    		 Endocrine Therapy
    Arm description
    		 Endocrine therapy (physicians’ choice) standard-of-care was administered according to package label until discontinuation criteria were met.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Standard Adjuvant Endocrine Therapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Oral liquid, Tablet
    Routes of administration
    Intramuscular use, Oral use, Subcutaneous use
    Dosage and administration details
    Endocrine therapy (physicians' choice) standard-of-care was administered according to package label until discontinuation criteria were met.

    Number of subjects in period 1
    		150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy
    Started
    2808
    2829
    Received at least one dose of study drug
    2791
    2800
    Completed
    650
    607
    Not completed
    2158
    2222
         Missing disposition data
    -
    1
         Consent withdrawn by subject
    119
    134
         On study treatment
    2027
    2074
         Lost to follow-up
    12
    13

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    150 mg Abemaciclib + Endocrine Therapy
    Reporting group description
    		 Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians’ choice) standard-of-care was administered according to package label until discontinuation criteria were met.

    Reporting group title
    Endocrine Therapy
    Reporting group description
    		 Endocrine therapy (physicians’ choice) standard-of-care was administered according to package label until discontinuation criteria were met.

    Reporting group values
    		 150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy Total
    Number of subjects
    		 2808 2829 5637
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 52.20 ( 11.26 ) 52.10 ( 11.20 ) -
    Gender categorical
    Units: Subjects
        Female
    		 2787 2814 5601
        Male
    		 21 15 36
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 355 378 733
        Not Hispanic or Latino
    		 1734 1738 3472
        Unknown or Not Reported
    		 719 713 1432
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 64 58 122
        Asian
    		 675 669 1344
        Native Hawaiian or Other Pacific Islander
    		 3 4 7
        Black or African American
    		 57 53 110
        White
    		 1947 1978 3925
        More than one race
    		 22 25 47
        Unknown or Not Reported
    		 40 42 82
    Region of Enrollment
    Units: Subjects
        Argentina
    		 77 68 145
        Australia
    		 108 109 217
        Austria
    		 22 20 42
        Belgium
    		 65 51 116
        Brazil
    		 144 153 297
        Canada
    		 28 16 44
        China
    		 187 170 357
        Czechia
    		 15 12 27
        Denmark
    		 54 58 112
        Finland
    		 45 49 94
        France
    		 86 101 187
        Germany
    		 148 152 300
        Greece
    		 74 64 138
        Hong Kong
    		 8 12 20
        Hungary
    		 24 28 52
        India
    		 59 53 112
        Israel
    		 39 38 77
        Italy
    		 72 59 131
        Japan
    		 181 196 377
        Mexico
    		 104 121 225
        Netherlands
    		 5 14 19
        New Zealand
    		 21 22 43
        Poland
    		 65 60 125
        Portugal
    		 21 16 37
        Puerto Rico
    		 1 3 4
        Romania
    		 53 60 113
        Russia
    		 66 73 139
        Saudi Arabia
    		 5 9 14
        Singapore
    		 11 21 32
        South Africa
    		 3 6 9
        South Korea
    		 122 123 245
        Spain
    		 144 148 292
        Sweden
    		 7 5 12
        Taiwan
    		 64 60 124
        Turkey
    		 125 110 235
        Ukraine
    		 54 51 105
        United Kingdom
    		 99 100 199
        United States
    		 402 418 820

    End points

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    End points reporting groups
    Reporting group title
    150 mg Abemaciclib + Endocrine Therapy
    Reporting group description
    		 Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians’ choice) standard-of-care was administered according to package label until discontinuation criteria were met.

    Reporting group title
    Endocrine Therapy
    Reporting group description
    		 Endocrine therapy (physicians’ choice) standard-of-care was administered according to package label until discontinuation criteria were met.

    Primary: Invasive Disease Free Survival (IDFS)

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    End point title
    		 Invasive Disease Free Survival (IDFS)
    End point description
    IDFS, as defined by the STEEP System, was measured from the date of randomization to the date of first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, death attributable to any cause. Analysis Population Description: All randomized participants (including the censored participants). 2672 participants were censored in "150 mg Abemaciclib + Endocrine Therapy," 2642 participants were censored in "Endocrine Therapy."
    End point type
    Primary
    End point timeframe
    Baseline to Recurrence or Death from Any Cause (Up to 32 Months)
    End point values
    		 150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy
    Number of subjects analysed
    2808 [1]
    2829 [2]
    Units: Months
        median (confidence interval 95%)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    Notes
    [1] - 9999 = NA, There were not enough events to compute a median or 95% confidence interval.
    [2] - 9999 = NA, There were not enough events to compute a median or 95% confidence interval.
    Statistical analysis title
    		 Invasive Disease Free Survival (IDFS)
    Comparison groups
    150 mg Abemaciclib + Endocrine Therapy v Endocrine Therapy
    Number of subjects included in analysis
    5637
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.00957
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.747
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.598
         upper limit
    		 0.932

    Secondary: IDFS for Participants with Ki-67 Index ≥20%

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    End point title
    		 IDFS for Participants with Ki-67 Index ≥20%
    End point description
    Outcome data will be provided after the study is completed.
    End point type
    Secondary
    End point timeframe
    Baseline to Recurrence or Death from Any Cause (Approximately 10 Years)
    End point values
    		 150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy
    Number of subjects analysed
    0 [3]
    0 [4]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [3] - Outcome data will be provided after the study is completed.
    [4] - Outcome data will be provided after the study is completed.
    No statistical analyses for this end point

    Secondary: Distant Relapse-Free Survival (DRFS)

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    End point title
    		 Distant Relapse-Free Survival (DRFS)
    End point description
    Distant relapse-free survival is defined as the time from randomization to distant recurrence or death from any cause, whichever occurs first. Analysis Population Description: All randomized participants (including the censored participants). 2702 participants were censored in "150 mg Abemaciclib + Endocrine Therapy," 2677 participants were censored in "Endocrine Therapy."
    End point type
    Secondary
    End point timeframe
    Baseline to Distant Recurrence or Death from Any Cause (Up to 32 Months)
    End point values
    		 150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy
    Number of subjects analysed
    2808 [5]
    2829 [6]
    Units: Months
        median (confidence interval 95%)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    Notes
    [5] - 9999 = NA, There were not enough events to compute a median or 95% confidence interval.
    [6] - 9999 = NA, There were not enough events to compute a median or 95% confidence interval.
    Statistical analysis title
    		 Distant Relapse-Free Survival (DRFS)
    Comparison groups
    150 mg Abemaciclib + Endocrine Therapy v Endocrine Therapy
    Number of subjects included in analysis
    5637
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.717
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.559
         upper limit
    		 0.92

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    Outcome data will be provided after the study is completed.
    End point type
    Secondary
    End point timeframe
    Baseline to Death from Any Cause (Approximately 10 Years)
    End point values
    		 150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy
    Number of subjects analysed
    0 [7]
    0 [8]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [7] - Outcome data will be provided after the study is completed.
    [8] - Outcome data will be provided after the study is completed.
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib

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    End point title
    		 Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib [9]
    End point description
    Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib Analysis Population Description: All randomized participants who received at least one dose of Abemaciclib and had evaluable PK data.
    End point type
    Secondary
    End point timeframe
    Day 1 (2 hours post-dose), Days 30, 60, 90 post-dose
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No inferential statistics were planned for this endpoint.
    End point values
    		 150 mg Abemaciclib + Endocrine Therapy
    Number of subjects analysed
    483
    Units: Nanograms per milliliter (ng/mL)
        geometric mean (geometric coefficient of variation)
    143 ( 110 )
    No statistical analyses for this end point

    Secondary: Change from Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B)

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    End point title
    		 Change from Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B)
    End point description
    Outcome data will be provided after the study is completed.
    End point type
    Secondary
    End point timeframe
    Baseline, Follow Up (Approximately 3 Years)
    End point values
    		 150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy
    Number of subjects analysed
    0 [10]
    0 [11]
    Units: Score on a scale
        least squares mean (standard error)
    ( )
    ( )
    Notes
    [10] - Outcome data will be provided after the study is completed.
    [11] - Outcome data will be provided after the study is completed.
    No statistical analyses for this end point

    Secondary: Change from Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES)

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    End point title
    		 Change from Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES)
    End point description
    Outcome data will be provided after the study is completed.
    End point type
    Secondary
    End point timeframe
    Baseline, Follow Up (Approximately 3 Years)]
    End point values
    		 150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy
    Number of subjects analysed
    0 [12]
    0 [13]
    Units: Score on a scale
        least squares mean (standard error)
    ( )
    ( )
    Notes
    [12] - Outcome data will be provided after the study is completed.
    [13] - Outcome data will be provided after the study is completed.
    No statistical analyses for this end point

    Secondary: Change from Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)

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    End point title
    		 Change from Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
    End point description
    Outcome data will be provided after the study is completed.
    End point type
    Secondary
    End point timeframe
    Baseline, Follow Up (Approximately 3 Years)]
    End point values
    		 150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy
    Number of subjects analysed
    0 [14]
    0 [15]
    Units: Score on a scale
        least squares mean (standard error)
    ( )
    ( )
    Notes
    [14] - Outcome data will be provided after the study is completed.
    [15] - Outcome data will be provided after the study is completed.
    No statistical analyses for this end point

    Secondary: Change from Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L)

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    End point title
    		 Change from Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L)
    End point description
    Outcome data will be provided after the study is completed.
    End point type
    Secondary
    End point timeframe
    Baseline, Follow Up (Approximately 3 Years)]
    End point values
    		 150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy
    Number of subjects analysed
    0 [16]
    0 [17]
    Units: Score on a scale
        least squares mean (standard error)
    ( )
    ( )
    Notes
    [16] - Outcome data will be provided after the study is completed.
    [17] - Outcome data will be provided after the study is completed.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline Up To 32 Months
    Adverse event reporting additional description
    I3Y-MC-JPCF
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    150 mg Abemaciclib + Endocrine Therapy
    Reporting group description
    		 Participants received Abemaciclib orally at 150 milligrams (mg) twice daily with at least 6 hours between doses for up to 2 years or until evidence of disease recurrence or other discontinuation criteria were met, whichever occurs first. Endocrine therapy (physicians’ choice) standard-of-care was administered according to package label until discontinuation criteria were met.

    Reporting group title
    Endocrine Therapy
    Reporting group description
    		 Endocrine therapy (physicians’ choice) standard-of-care was administered according to package label until discontinuation criteria were met.

    Serious adverse events
    		 150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    344 / 2791 (12.33%)
    202 / 2800 (7.21%)
         number of deaths (all causes)
    38
    36
         number of deaths resulting from adverse events
    2
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    acute lymphocytic leukaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cervix carcinoma
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [1]
    0 / 2770 (0.00%)
    2 / 2785 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colon cancer
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colorectal carcinoma stage 0
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    endometrial neoplasm
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [2]
    0 / 2770 (0.00%)
    1 / 2785 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fibroadenoma of breast
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal adenocarcinoma
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malignant melanoma
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    meningioma benign
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    non-small cell lung cancer
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    papillary thyroid cancer
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thyroid adenoma
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thyroid cancer
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tumour pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    uterine leiomyoma
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [3]
    1 / 2770 (0.04%)
    2 / 2785 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    deep vein thrombosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    16 / 2791 (0.57%)
    3 / 2800 (0.11%)
         occurrences causally related to treatment / all
    12 / 17
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    embolism
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haematoma
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypertension
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    jugular vein thrombosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lymphoedema
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    5 / 2791 (0.18%)
    3 / 2800 (0.11%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peripheral artery thrombosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombophlebitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombophlebitis superficial
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (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
    capsular contracture associated with breast implant
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    chest pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 2791 (0.14%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fatigue
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    general physical health deterioration
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 2791 (0.14%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    hyperplasia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    impaired healing
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    3 / 2800 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    inflammation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    non-cardiac chest pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    7 / 2791 (0.25%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    4 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sudden death
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    anaphylactic reaction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    drug hypersensitivity
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (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
    adenomyosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [4]
    1 / 2770 (0.04%)
    0 / 2785 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast atrophy
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast calcifications
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast discharge
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast disorder
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast fibrosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast inflammation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast mass
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast necrosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast swelling
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cervical dysplasia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [5]
    2 / 2770 (0.07%)
    0 / 2785 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    endometrial disorder
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [6]
    0 / 2770 (0.00%)
    1 / 2785 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    endometrial hypertrophy
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [7]
    0 / 2770 (0.00%)
    2 / 2785 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    endometrial thickening
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [8]
    1 / 2770 (0.04%)
    1 / 2785 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    endometriosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [9]
    0 / 2770 (0.00%)
    1 / 2785 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fibrocystic breast disease
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    metrorrhagia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [10]
    0 / 2770 (0.00%)
    1 / 2785 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ovarian cyst
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [11]
    0 / 2770 (0.00%)
    3 / 2785 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pelvic haematoma
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    uterine polyp
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [12]
    2 / 2770 (0.07%)
    3 / 2785 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    asthma
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dyspnoea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypoxia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    interstitial lung disease
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    organising pneumonia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pleural effusion
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia aspiration
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    7 / 2791 (0.25%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    6 / 7
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    16 / 2791 (0.57%)
    3 / 2800 (0.11%)
         occurrences causally related to treatment / all
    14 / 16
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    respiratory failure
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    bipolar disorder
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    confusional state
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    delirium
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    depression
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mania
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mental disorder
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    psychotic disorder
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    suicide attempt
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    device failure
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    5 / 2791 (0.18%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    3 / 5
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    5 / 2791 (0.18%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    4 / 5
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    blood creatinine increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    international normalised ratio increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    occult blood
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    transaminases increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    abdominal wound dehiscence
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    alcohol poisoning
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ankle fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    3 / 2800 (0.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast procedural complication
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    clavicle fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    exposure during pregnancy
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fall
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    femoral neck fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    foot fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hip fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    humerus fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    incisional hernia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    jaw fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    joint injury
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ligament rupture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    post procedural haematoma
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    post procedural haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    postoperative adhesion
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    postoperative thoracic procedure complication
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    postoperative wound complication
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    procedural complication
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    radiation pneumonitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    radius fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rib fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    skin flap necrosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spinal fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thermal burn
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    wound complication
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    wound dehiscence
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    4 / 2800 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    wound necrosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    wrist fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    acute left ventricular failure
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    angina pectoris
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    atrial fibrillation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    6 / 2791 (0.21%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    atrioventricular block complete
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cardiac arrest
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    cardiac failure
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 2791 (0.14%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    cardiotoxicity
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    coronary artery disease
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    myocardial infarction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 2791 (0.14%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    myocardial ischaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pericarditis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sinus tachycardia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    stress cardiomyopathy
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    supraventricular tachycardia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ventricular fibrillation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    carotid artery aneurysm
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    carpal tunnel syndrome
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebral haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    cerebral infarction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebral ischaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebral venous thrombosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebrospinal fluid leakage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebrovascular accident
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    dizziness
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    extrapyramidal disorder
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    headache
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hemiparesis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ischaemic stroke
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    memory impairment
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    monoparesis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    movement disorder
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nerve compression
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neuropathy
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    presyncope
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    subarachnoid haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    syncope
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 2791 (0.14%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    trigeminal neuralgia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    8 / 2791 (0.29%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    4 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bone marrow oedema
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    disseminated intravascular coagulation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    febrile neutropenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 2791 (0.14%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    leukopenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 2791 (0.14%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lymphadenopathy mediastinal
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutropenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancytopenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombocytopenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 2791 (0.14%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    3 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    tympanic membrane perforation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vertigo
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    angle closure glaucoma
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cataract
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    eyelid ptosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    macular hole
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    macular pseudohole
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    retinal detachment
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    6 / 2791 (0.21%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    anal fissure
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    anal fistula
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    chronic gastritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    3 / 2800 (0.11%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colitis ischaemic
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dental caries
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diarrhoea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    15 / 2791 (0.54%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    13 / 18
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    enteritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    food poisoning
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastritis erosive
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal fistula
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemorrhoidal haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemorrhoids
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    inguinal hernia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intestinal obstruction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    large intestine polyp
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nausea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophagitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancreatitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    6 / 2791 (0.21%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancreatitis acute
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peritoneal adhesions
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    stomatitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    umbilical hernia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    biliary colic
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholecystitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    10 / 2791 (0.36%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    1 / 10
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholecystitis acute
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholelithiasis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    3 / 2800 (0.11%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    drug-induced liver injury
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic cirrhosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic function abnormal
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    jaundice
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    erythema
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    acute kidney injury
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 2791 (0.14%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nephrolithiasis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    renal failure
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    renal impairment
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tubulointerstitial nephritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         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
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fistula
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    flank pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intervertebral disc protrusion
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    3 / 2800 (0.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    myositis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neck pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    osteoarthritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    osteonecrosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rheumatoid arthritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rotator cuff syndrome
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spinal osteoarthritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tenosynovitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    abdominal infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    abscess
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    anal abscess
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    appendicitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    appendicitis perforated
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bacteraemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    biliary tract infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast abscess
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast cellulitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    5 / 2791 (0.18%)
    4 / 2800 (0.14%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bronchitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    campylobacter gastroenteritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    11 / 2791 (0.39%)
    9 / 2800 (0.32%)
         occurrences causally related to treatment / all
    1 / 13
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cellulitis staphylococcal
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    clostridium colitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    clostridium difficile colitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    coronavirus infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    device related infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diverticulitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    5 / 2800 (0.18%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ear infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    erysipelas
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    5 / 2791 (0.18%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    3 / 9
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    escherichia pyelonephritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    febrile infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastroenteritis clostridial
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatitis e
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    implant site infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infective pulmonary exacerbation of cystic fibrosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    influenza
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    7 / 2791 (0.25%)
    3 / 2800 (0.11%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    intervertebral discitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    laryngitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lower respiratory tract infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lymphangitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mastitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 2791 (0.11%)
    5 / 2800 (0.18%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mastoiditis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    meningitis viral
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nasopharyngitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutropenic infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    osteomyelitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peritonitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    23 / 2791 (0.82%)
    14 / 2800 (0.50%)
         occurrences causally related to treatment / all
    10 / 23
    2 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    pneumonia bacterial
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia influenzal
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia streptococcal
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    post procedural cellulitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    post procedural infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    postoperative wound infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pyelonephritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    respiratory tract infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    5 / 2791 (0.18%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    septic shock
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    skin infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    soft tissue infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tuberculosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    upper respiratory tract infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    6 / 2791 (0.21%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    3 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    12 / 2791 (0.43%)
    4 / 2800 (0.14%)
         occurrences causally related to treatment / all
    1 / 12
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urosepsis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    viral infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    wound infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 2791 (0.07%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    dehydration
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    7 / 2791 (0.25%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    5 / 9
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    food intolerance
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypercalcaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperglycaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypocalcaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypokalaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 2791 (0.14%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyponatraemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    2 / 2800 (0.07%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypophosphataemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypovolaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 2791 (0.00%)
    1 / 2800 (0.04%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    metabolic acidosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 2791 (0.04%)
    0 / 2800 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 150 mg Abemaciclib + Endocrine Therapy Endocrine Therapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2723 / 2791 (97.56%)
    2318 / 2800 (82.79%)
    Vascular disorders
    hot flush
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    393 / 2791 (14.08%)
    587 / 2800 (20.96%)
         occurrences all number
    432
    678
    hypertension
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    101 / 2791 (3.62%)
    130 / 2800 (4.64%)
         occurrences all number
    120
    158
    hypotension
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    33 / 2791 (1.18%)
    14 / 2800 (0.50%)
         occurrences all number
    33
    15
    lymphoedema
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    282 / 2791 (10.10%)
    207 / 2800 (7.39%)
         occurrences all number
    295
    225
    Surgical and medical procedures
    breast reconstruction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    28 / 2791 (1.00%)
    22 / 2800 (0.79%)
         occurrences all number
    28
    25
    General disorders and administration site conditions
    axillary pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    28 / 2791 (1.00%)
    39 / 2800 (1.39%)
         occurrences all number
    28
    41
    chest pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    35 / 2791 (1.25%)
    35 / 2800 (1.25%)
         occurrences all number
    40
    36
    chills
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    49 / 2791 (1.76%)
    18 / 2800 (0.64%)
         occurrences all number
    55
    18
    fatigue
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1073 / 2791 (38.45%)
    433 / 2800 (15.46%)
         occurrences all number
    1434
    522
    influenza like illness
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    141 / 2791 (5.05%)
    112 / 2800 (4.00%)
         occurrences all number
    180
    152
    malaise
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    88 / 2791 (3.15%)
    29 / 2800 (1.04%)
         occurrences all number
    109
    29
    mucosal inflammation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    72 / 2791 (2.58%)
    21 / 2800 (0.75%)
         occurrences all number
    90
    32
    oedema peripheral
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    169 / 2791 (6.06%)
    103 / 2800 (3.68%)
         occurrences all number
    200
    119
    pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    60 / 2791 (2.15%)
    53 / 2800 (1.89%)
         occurrences all number
    64
    58
    peripheral swelling
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    51 / 2791 (1.83%)
    53 / 2800 (1.89%)
         occurrences all number
    58
    61
    pyrexia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    227 / 2791 (8.13%)
    114 / 2800 (4.07%)
         occurrences all number
    299
    130
    Reproductive system and breast disorders
    breast pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    95 / 2791 (3.40%)
    120 / 2800 (4.29%)
         occurrences all number
    104
    133
    erectile dysfunction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [13]
    1 / 21 (4.76%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    vaginal discharge
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [14]
    26 / 2770 (0.94%)
    39 / 2785 (1.40%)
         occurrences all number
    27
    42
    vulvovaginal dryness
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [15]
    78 / 2770 (2.82%)
    117 / 2785 (4.20%)
         occurrences all number
    80
    127
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    337 / 2791 (12.07%)
    193 / 2800 (6.89%)
         occurrences all number
    407
    228
    dyspnoea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    139 / 2791 (4.98%)
    77 / 2800 (2.75%)
         occurrences all number
    154
    86
    epistaxis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    49 / 2791 (1.76%)
    8 / 2800 (0.29%)
         occurrences all number
    52
    10
    nasal congestion
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    34 / 2791 (1.22%)
    29 / 2800 (1.04%)
         occurrences all number
    37
    33
    oropharyngeal pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    115 / 2791 (4.12%)
    76 / 2800 (2.71%)
         occurrences all number
    142
    91
    pneumonitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    36 / 2791 (1.29%)
    10 / 2800 (0.36%)
         occurrences all number
    36
    10
    productive cough
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    45 / 2791 (1.61%)
    25 / 2800 (0.89%)
         occurrences all number
    53
    28
    rhinitis allergic
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    40 / 2791 (1.43%)
    40 / 2800 (1.43%)
         occurrences all number
    41
    42
    rhinorrhoea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    29 / 2791 (1.04%)
    15 / 2800 (0.54%)
         occurrences all number
    31
    16
    Psychiatric disorders
    anxiety
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    81 / 2791 (2.90%)
    113 / 2800 (4.04%)
         occurrences all number
    84
    116
    depression
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    134 / 2791 (4.80%)
    116 / 2800 (4.14%)
         occurrences all number
    142
    120
    insomnia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    208 / 2791 (7.45%)
    218 / 2800 (7.79%)
         occurrences all number
    251
    246
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    265 / 2791 (9.49%)
    119 / 2800 (4.25%)
         occurrences all number
    345
    149
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    257 / 2791 (9.21%)
    106 / 2800 (3.79%)
         occurrences all number
    323
    122
    blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    83 / 2791 (2.97%)
    47 / 2800 (1.68%)
         occurrences all number
    98
    56
    blood creatinine increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    277 / 2791 (9.92%)
    17 / 2800 (0.61%)
         occurrences all number
    396
    22
    gamma-glutamyltransferase increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    70 / 2791 (2.51%)
    24 / 2800 (0.86%)
         occurrences all number
    80
    28
    weight decreased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    79 / 2791 (2.83%)
    19 / 2800 (0.68%)
         occurrences all number
    88
    20
    weight increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    29 / 2791 (1.04%)
    46 / 2800 (1.64%)
         occurrences all number
    32
    47
    Injury, poisoning and procedural complications
    contusion
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    42 / 2791 (1.50%)
    37 / 2800 (1.32%)
         occurrences all number
    51
    38
    fall
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    52 / 2791 (1.86%)
    36 / 2800 (1.29%)
         occurrences all number
    61
    43
    procedural pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    73 / 2791 (2.62%)
    53 / 2800 (1.89%)
         occurrences all number
    78
    64
    Cardiac disorders
    palpitations
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    54 / 2791 (1.93%)
    20 / 2800 (0.71%)
         occurrences all number
    62
    22
    Nervous system disorders
    dizziness
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    274 / 2791 (9.82%)
    158 / 2800 (5.64%)
         occurrences all number
    333
    188
    dysgeusia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    103 / 2791 (3.69%)
    8 / 2800 (0.29%)
         occurrences all number
    121
    8
    headache
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    482 / 2791 (17.27%)
    359 / 2800 (12.82%)
         occurrences all number
    809
    553
    memory impairment
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    29 / 2791 (1.04%)
    22 / 2800 (0.79%)
         occurrences all number
    32
    22
    neuropathy
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    193 / 2791 (6.92%)
    203 / 2800 (7.25%)
         occurrences all number
    221
    234
    taste disorder
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    36 / 2791 (1.29%)
    4 / 2800 (0.14%)
         occurrences all number
    36
    4
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    634 / 2791 (22.72%)
    88 / 2800 (3.14%)
         occurrences all number
    862
    113
    leukopenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1026 / 2791 (36.76%)
    171 / 2800 (6.11%)
         occurrences all number
    1706
    244
    lymphopenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    372 / 2791 (13.33%)
    94 / 2800 (3.36%)
         occurrences all number
    527
    118
    neutropenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1246 / 2791 (44.64%)
    140 / 2800 (5.00%)
         occurrences all number
    2316
    214
    thrombocytopenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    341 / 2791 (12.22%)
    39 / 2800 (1.39%)
         occurrences all number
    528
    48
    Ear and labyrinth disorders
    vertigo
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    70 / 2791 (2.51%)
    47 / 2800 (1.68%)
         occurrences all number
    93
    55
    Eye disorders
    dry eye
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    71 / 2791 (2.54%)
    28 / 2800 (1.00%)
         occurrences all number
    76
    31
    lacrimation increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    137 / 2791 (4.91%)
    10 / 2800 (0.36%)
         occurrences all number
    158
    10
    vision blurred
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    46 / 2791 (1.65%)
    24 / 2800 (0.86%)
         occurrences all number
    52
    25
    Gastrointestinal disorders
    abdominal distension
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    75 / 2791 (2.69%)
    27 / 2800 (0.96%)
         occurrences all number
    90
    28
    abdominal pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    945 / 2791 (33.86%)
    226 / 2800 (8.07%)
         occurrences all number
    1974
    275
    constipation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    288 / 2791 (10.32%)
    142 / 2800 (5.07%)
         occurrences all number
    377
    161
    diarrhoea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2294 / 2791 (82.19%)
    199 / 2800 (7.11%)
         occurrences all number
    11663
    288
    dry mouth
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    94 / 2791 (3.37%)
    25 / 2800 (0.89%)
         occurrences all number
    103
    27
    dyspepsia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    205 / 2791 (7.35%)
    61 / 2800 (2.18%)
         occurrences all number
    264
    66
    flatulence
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    84 / 2791 (3.01%)
    11 / 2800 (0.39%)
         occurrences all number
    95
    12
    gastritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    58 / 2791 (2.08%)
    31 / 2800 (1.11%)
         occurrences all number
    65
    34
    gastrooesophageal reflux disease
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    74 / 2791 (2.65%)
    45 / 2800 (1.61%)
         occurrences all number
    76
    47
    haemorrhoids
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    68 / 2791 (2.44%)
    28 / 2800 (1.00%)
         occurrences all number
    82
    28
    mouth ulceration
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    39 / 2791 (1.40%)
    3 / 2800 (0.11%)
         occurrences all number
    48
    3
    nausea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    779 / 2791 (27.91%)
    222 / 2800 (7.93%)
         occurrences all number
    1203
    274
    stomatitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    154 / 2791 (5.52%)
    30 / 2800 (1.07%)
         occurrences all number
    212
    39
    toothache
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    49 / 2791 (1.76%)
    42 / 2800 (1.50%)
         occurrences all number
    55
    50
    vomiting
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    454 / 2791 (16.27%)
    117 / 2800 (4.18%)
         occurrences all number
    744
    144
    Hepatobiliary disorders
    hepatic steatosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    41 / 2791 (1.47%)
    35 / 2800 (1.25%)
         occurrences all number
    42
    35
    Skin and subcutaneous tissue disorders
    alopecia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    254 / 2791 (9.10%)
    53 / 2800 (1.89%)
         occurrences all number
    266
    53
    dermatitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    28 / 2791 (1.00%)
    11 / 2800 (0.39%)
         occurrences all number
    31
    13
    dry skin
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    102 / 2791 (3.65%)
    48 / 2800 (1.71%)
         occurrences all number
    108
    51
    eczema
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    29 / 2791 (1.04%)
    28 / 2800 (1.00%)
         occurrences all number
    32
    31
    erythema
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    38 / 2791 (1.36%)
    26 / 2800 (0.93%)
         occurrences all number
    43
    28
    hyperhidrosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    29 / 2791 (1.04%)
    32 / 2800 (1.14%)
         occurrences all number
    33
    34
    nail disorder
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    43 / 2791 (1.54%)
    4 / 2800 (0.14%)
         occurrences all number
    45
    4
    night sweats
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    40 / 2791 (1.43%)
    28 / 2800 (1.00%)
         occurrences all number
    43
    31
    onychoclasis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    46 / 2791 (1.65%)
    7 / 2800 (0.25%)
         occurrences all number
    54
    7
    pruritus
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    219 / 2791 (7.85%)
    110 / 2800 (3.93%)
         occurrences all number
    298
    121
    rash
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    272 / 2791 (9.75%)
    106 / 2800 (3.79%)
         occurrences all number
    332
    132
    Renal and urinary disorders
    dysuria
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    46 / 2791 (1.65%)
    25 / 2800 (0.89%)
         occurrences all number
    53
    29
    Endocrine disorders
    hypothyroidism
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    28 / 2791 (1.00%)
    34 / 2800 (1.21%)
         occurrences all number
    29
    34
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    571 / 2791 (20.46%)
    876 / 2800 (31.29%)
         occurrences all number
    705
    1117
    arthritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    9 / 2791 (0.32%)
    29 / 2800 (1.04%)
         occurrences all number
    10
    33
    back pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    223 / 2791 (7.99%)
    271 / 2800 (9.68%)
         occurrences all number
    277
    317
    bone pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    62 / 2791 (2.22%)
    93 / 2800 (3.32%)
         occurrences all number
    75
    102
    joint range of motion decreased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    24 / 2791 (0.86%)
    29 / 2800 (1.04%)
         occurrences all number
    35
    40
    joint stiffness
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    22 / 2791 (0.79%)
    56 / 2800 (2.00%)
         occurrences all number
    25
    59
    muscle spasms
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    134 / 2791 (4.80%)
    100 / 2800 (3.57%)
         occurrences all number
    180
    121
    muscular weakness
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    29 / 2791 (1.04%)
    16 / 2800 (0.57%)
         occurrences all number
    31
    16
    musculoskeletal chest pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    70 / 2791 (2.51%)
    72 / 2800 (2.57%)
         occurrences all number
    77
    76
    musculoskeletal pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    111 / 2791 (3.98%)
    154 / 2800 (5.50%)
         occurrences all number
    120
    170
    musculoskeletal stiffness
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    32 / 2791 (1.15%)
    33 / 2800 (1.18%)
         occurrences all number
    34
    37
    myalgia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    167 / 2791 (5.98%)
    163 / 2800 (5.82%)
         occurrences all number
    193
    185
    neck pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    48 / 2791 (1.72%)
    59 / 2800 (2.11%)
         occurrences all number
    49
    64
    osteopenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    30 / 2791 (1.07%)
    32 / 2800 (1.14%)
         occurrences all number
    30
    32
    osteoporosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    45 / 2791 (1.61%)
    71 / 2800 (2.54%)
         occurrences all number
    45
    75
    pain in extremity
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    245 / 2791 (8.78%)
    274 / 2800 (9.79%)
         occurrences all number
    292
    354
    Infections and infestations
    bronchitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    42 / 2791 (1.50%)
    40 / 2800 (1.43%)
         occurrences all number
    50
    44
    cellulitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    37 / 2791 (1.33%)
    28 / 2800 (1.00%)
         occurrences all number
    43
    31
    conjunctivitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    55 / 2791 (1.97%)
    30 / 2800 (1.07%)
         occurrences all number
    63
    34
    gastroenteritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    73 / 2791 (2.62%)
    32 / 2800 (1.14%)
         occurrences all number
    84
    36
    herpes zoster
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    34 / 2791 (1.22%)
    39 / 2800 (1.39%)
         occurrences all number
    34
    39
    influenza
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    110 / 2791 (3.94%)
    102 / 2800 (3.64%)
         occurrences all number
    139
    135
    nasopharyngitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    231 / 2791 (8.28%)
    186 / 2800 (6.64%)
         occurrences all number
    324
    285
    oral herpes
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    29 / 2791 (1.04%)
    8 / 2800 (0.29%)
         occurrences all number
    34
    9
    pharyngitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    26 / 2791 (0.93%)
    29 / 2800 (1.04%)
         occurrences all number
    29
    33
    pneumonia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    45 / 2791 (1.61%)
    19 / 2800 (0.68%)
         occurrences all number
    46
    19
    sinusitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    69 / 2791 (2.47%)
    51 / 2800 (1.82%)
         occurrences all number
    76
    67
    skin infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    33 / 2791 (1.18%)
    23 / 2800 (0.82%)
         occurrences all number
    36
    26
    upper respiratory tract infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    280 / 2791 (10.03%)
    214 / 2800 (7.64%)
         occurrences all number
    393
    323
    urinary tract infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    278 / 2791 (9.96%)
    167 / 2800 (5.96%)
         occurrences all number
    368
    235
    vaginal infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [16]
    30 / 2770 (1.08%)
    18 / 2785 (0.65%)
         occurrences all number
    37
    21
    viral infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    28 / 2791 (1.00%)
    14 / 2800 (0.50%)
         occurrences all number
    32
    15
    vulvovaginal candidiasis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [17]
    29 / 2770 (1.05%)
    20 / 2785 (0.72%)
         occurrences all number
    33
    31
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    312 / 2791 (11.18%)
    54 / 2800 (1.93%)
         occurrences all number
    352
    57
    dehydration
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    33 / 2791 (1.18%)
    7 / 2800 (0.25%)
         occurrences all number
    39
    7
    hypercalcaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    49 / 2791 (1.76%)
    32 / 2800 (1.14%)
         occurrences all number
    58
    42
    hypercholesterolaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    48 / 2791 (1.72%)
    61 / 2800 (2.18%)
         occurrences all number
    53
    67
    hyperglycaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    37 / 2791 (1.33%)
    43 / 2800 (1.54%)
         occurrences all number
    51
    53
    hypertriglyceridaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    67 / 2791 (2.40%)
    45 / 2800 (1.61%)
         occurrences all number
    82
    63
    hyperuricaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    33 / 2791 (1.18%)
    13 / 2800 (0.46%)
         occurrences all number
    44
    14
    hypoalbuminaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    30 / 2791 (1.07%)
    12 / 2800 (0.43%)
         occurrences all number
    39
    17
    hypokalaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    105 / 2791 (3.76%)
    22 / 2800 (0.79%)
         occurrences all number
    126
    31
    vitamin d deficiency
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    29 / 2791 (1.04%)
    33 / 2800 (1.18%)
         occurrences all number
    33
    37
    Notes
    [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
    [17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: There are gender specific adverse events occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Oct 2017
    Safety management updates including toxicity dose adjustment guidance for ALT increases; exclusion of participants with a history of venous thromboembolism (VTE); updates to protocol selection criteria to better align with global clinical practice
    29 Jun 2018
    Increase in sample size from 3580 to 4580 participants; exclusion of participants with inflammatory breast cancer; recurrence tissue biomarker sample changed to mandatory for participants that undergo biopsy; updated to collect SAEs in both arms regardless of causality or relatedness through year 5; added section on safety monitoring for VTE
    19 Dec 2018
    Updated the ITT population to include participants in Cohort 1 and Cohort 2; modified VTE safety monitoring language including the addition of Appendix 12 guidance for management of VTE while on study; included AST in the hepatic function safety monitoring; number of events required at final IDFS was updated from approximately 345 to approximately 390 from across Cohort 1 and Cohort 2 to yield approximately 85% statistical power
    25 Jun 2019
    Update on the timing of the efficacy interim analyses to ensure the data are sufficiently mature; added interstitial lung disease (ILD)/pneumonitis as a new adverse drug reaction; added safety monitoring guidance related to ILD/pneumonitis
    18 Sep 2019
    Changed protocol language from ‘capsules’ to ‘tablets or capsules’ to allow for supply chain planning in the event the study switches from capsules formulation to tablets

    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
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