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    Clinical Trial Results:
    PALbociclib CoLlaborative Adjuvant Study: A randomized phase III trial of Palbociclib with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy alone for hormone receptor positive (HR+) / human epidermal growth factor receptor 2 (HER2)-negative early breast cancer

    Summary
    EudraCT number
    2014-005181-30
    Trial protocol
    AT   ES   IE   HU   PT   DE   SE   NL   BE   PL   GB   IT  
    Global end of trial date

    Results information
    Results version number
    v1(current)
    This version publication date
    11 Jan 2022
    First version publication date
    11 Jan 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    AFT-05/ABCSG-42/BIG_14-03
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02513394
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    IND number: 126003
    Sponsors
    Sponsor organisation name
    ABCSG GmbH
    Sponsor organisation address
    Nußdorfer Platz 8/12, Vienna, Austria, 1190
    Public contact
    Trial Office (Studienzentrale), Austrian Breast & Colorectal Cancer Study Group (ABCSG) , +43 14089230, info@abcsg.at
    Scientific contact
    Prof. Michael Gnant , Austrian Breast & Colorectal Cancer Study Group (ABCSG) , +43 14089230, info@abcsg.at
    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
    20 Nov 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Nov 2020
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To compare invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC).
    Protection of trial subjects
    A dedicated IDMC was established to regularly review patient safety data and provide recommendations to the Steering Committee during the active treatment phase. In addition, dedicated Medical Monitors are assigend for ongoing support to safeguard patient safety and well being by providing immediate assistance on any clinical / medical questions. The study specific Informed Consent Forms include language on patient advocacy, available 24/7 contacts and patient cards were provided to participants, containing important contact details. During the COVID-19 pandemic, additional measures have been set-up to allow for high quality patient care despite fewer on-site visits or restrictions in clinic routine (e.g. direct IP shipments to patients where needed, safety assessments by the sponsors, study PIs and drug provider to provide further guidance on assessments, vaccinations etc.).
    Background therapy
    Background therapy (endocrine therapy) as NIMP: According to the EU Guidance for IMP & NIMP (Annex 2, section 2a) the agents to be used are authorized products and a particular brand is not defined in the study protocol. Locally obtained commercial supply will be administered to the patients at the discretion of the principal investigator as well as according to standard institutional or regional practice. - Tamoxifen - Non-steroidal aromatase-inhibitors (anastrozole, letrozole) - Steroidal aromatase inhibitor (exemestane) - LHRH agonists in combination with tamoxifen or AI No additional information is required.
    Evidence for comparator
    Yes
    Actual start date of recruitment
    01 Sep 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Scientific research
    Long term follow-up duration
    8 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 27
    Country: Number of subjects enrolled
    Poland: 115
    Country: Number of subjects enrolled
    Portugal: 84
    Country: Number of subjects enrolled
    Spain: 1136
    Country: Number of subjects enrolled
    Sweden: 43
    Country: Number of subjects enrolled
    United Kingdom: 213
    Country: Number of subjects enrolled
    Austria: 479
    Country: Number of subjects enrolled
    Belgium: 134
    Country: Number of subjects enrolled
    Germany: 138
    Country: Number of subjects enrolled
    Hungary: 173
    Country: Number of subjects enrolled
    Ireland: 148
    Country: Number of subjects enrolled
    Italy: 117
    Country: Number of subjects enrolled
    Australia: 484
    Country: Number of subjects enrolled
    Canada: 194
    Country: Number of subjects enrolled
    Israel: 51
    Country: Number of subjects enrolled
    Japan: 45
    Country: Number of subjects enrolled
    Korea, Republic of: 33
    Country: Number of subjects enrolled
    Mexico: 37
    Country: Number of subjects enrolled
    Switzerland: 150
    Country: Number of subjects enrolled
    Taiwan: 42
    Country: Number of subjects enrolled
    United States: 2845
    Worldwide total number of subjects
    6688
    EEA total number of subjects
    2594
    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)
    5421
    From 65 to 84 years
    1251
    85 years and over
    16

    Subject disposition

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    Recruitment
    Recruitment details
    Recruitment period started on 1-Sep-2015 and a global enrollment of 4.600 patients within 3 years was planned. Throughout the study, sample size was increased to 5.600 patients and the recruitment period concluded on 30-Nov-2018. IxRS patient management system was used and patients were randomized 1:1 into one of the two treatment arms.

    Pre-assignment
    Screening details
    Eligibility was carefully assessed by study sites, based on the protocol specified inclusion and exclusion criteria, local screening logs were kept at study sites. Patients were entered into the IxRS system upon screening (to allow for patient ID assignment prior to randomization, in order to label and track the mandatory biospecimen accordingly).

    Pre-assignment period milestones
    Number of subjects started
    6688
    Number of subjects completed
    5761

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Consent withdrawn by subject: 35
    Reason: Number of subjects
    declined to participate: 259
    Reason: Number of subjects
    not meeting inclusion criteria: 466
    Reason: Number of subjects
    Other: 167
    Period 1
    Period 1 title
    overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Palbociclib plus endocrine therapy
    Arm description
    palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years
    Arm type
    Experimental

    Investigational medicinal product name
    Palbociclib
    Investigational medicinal product code
    PD-0332991-00
    Other name
    Ibrance, PD-332,991
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    125mg orally once daily, day 1 to day 21 followed by 7 days off treatment in a 28-day cycle for a total of 2 years

    Investigational medicinal product name
    Palbociclib
    Investigational medicinal product code
    PD-0332991-00
    Other name
    Ibrance, PD-332,991
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    100mg orally once daily, day 1 to day 21 followed bby 7 days off. Only be administrated in case of first dose reduction (Level -1) from 125mg to 100mg due to toxicity, dose interruption or cycle delay when treatment is resumed.

    Investigational medicinal product name
    Palbociclib
    Investigational medicinal product code
    PD-0332991-00
    Other name
    Ibrance, PD-332,991
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    75mg orally once daily, day 1 to day 21 followed by 7 days off. Only be administrated in case of second dose reduction (Level -2) from initally 125mg to 100mg to final 75mg due to toxicity, dose interruption or cycle delay when treatment is resumed.

    Arm title
    Endocrine therapy
    Arm description
    standard adjuvant endocrine therapy for a duration of at least 5 years
    Arm type
    NIMP background treatment

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1 [1]
    Palbociclib plus endocrine therapy Endocrine therapy
    Started
    2884
    2877
    Completed
    2475
    2507
    Not completed
    409
    370
         Adverse event, serious fatal
    100
    76
         Consent withdrawn by subject
    289
    285
         Other
    13
    7
         Lost to follow-up
    7
    2
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Several patients started (hence, were enrolled) but didn't complete the pre-assignment period due to reasons given in the pre-assignment section.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Palbociclib plus endocrine therapy
    Reporting group description
    palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years

    Reporting group title
    Endocrine therapy
    Reporting group description
    standard adjuvant endocrine therapy for a duration of at least 5 years

    Reporting group values
    Palbociclib plus endocrine therapy Endocrine therapy Total
    Number of subjects
    2884 2877 5761
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    2397 2385 4782
        From 65-84 years
    482 488 970
        85 years and over
    5 4 9
    Age continuous
    Units: years
        median (full range (min-max))
    52 (25 to 90) 52 (22 to 85) -
    Gender categorical
    Units: Subjects
        Female
    2867 2858 5725
        Male
    17 19 36
    Anatomic stage
    Units: Subjects
        I/IIA
    513 519 1032
        IIB/III
    2370 2358 4728
        Unknown
    1 0 1
    T-stage
    Assessed by pathological staging or by clinical staging if pre-operative therapy was given with the higher stage presented in this table
    Units: Subjects
        T0/T1/Tis/TX
    558 501 1059
        T2
    1603 1636 3239
        T3/T4
    722 740 1462
        Unknown
    1 0 1
    N-stage
    Units: Subjects
        N0
    365 385 750
        N1
    1431 1411 2842
        N2
    700 709 1409
        N3
    386 372 758
        NX
    1 0 1
        Unknown
    1 0 1
    Tumor grade
    Units: Subjects
        G1/G2
    1926 1971 3897
        G3
    836 769 1605
        GX
    118 137 255
        Unknown
    4 0 4
    Neo/adjuvant chemotherapy
    Units: Subjects
        No
    499 507 1006
        Yes
    2384 2370 4754
        Unknown
    1 0 1
    Menopausal status
    Units: Subjects
        Postmenopausal
    1562 1534 3096
        Premenopausal (including perimenopausal)
    1303 1323 2626
        Not applicable (male patient)
    17 19 36
        Unknown
    2 1 3

    End points

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    End points reporting groups
    Reporting group title
    Palbociclib plus endocrine therapy
    Reporting group description
    palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years

    Reporting group title
    Endocrine therapy
    Reporting group description
    standard adjuvant endocrine therapy for a duration of at least 5 years

    Subject analysis set title
    ITT
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    The ITT population was comprised of all randomized patients, including those who did not start palbociclib or endocrine treatment. This population provided the basis for the main efficacy analyses. Randomized patients consisted of all patients who have given their written informed consent and for whom there was confirmation of successful allocation of a randomization number through the IxRS. Patients who withdrew informed consent for all follow-up and for all data collected until the time of withdrawal were excluded from all analyses. Patients were analysed according to the treatment group to which they were randomized.

    Subject analysis set title
    Safety
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    For the purposes of evaluating and monitoring AEs and patient safety, the SAF population was defined as all randomized patients, excluding those who did not start palbociclib or endocrine treatment, i.e. as-treated. Patients were analysed according to the treatment actually received. Randomized patients who wrongly received IP palbociclib at any time point were included in the SAF population as palbociclib patients (Arm A). Patients randomized to the palbociclib arm, who never received palbociclib, but received endocrine therapy, were included in the SAF population as endocrine therapy patients (Arm B). Randomized patients for whom it is unclear (due to missing or inconsistent data entry) whether they took treatment were included in the SAF population as treated according to their randomized arm.

    Primary: iDFS

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    End point title
    iDFS
    End point description
    The primary endpoint was invasive disease free survival (iDFS), using STEEP criteria defined as the time from randomization to the date of first event (plus one day): local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second primary invasive cancer of non-breast origin or death from any cause. Surviving patients who are event-free were censored at: the date of last disease assessment, or withdrawal of consent to be followed, whichever occurs first. Survival rate estimates at 4 years with 2-sided 95% confidence intervals were calculated by Kaplan-Meier method.
    End point type
    Primary
    End point timeframe
    Until the date of awareness of the 469th event
    End point values
    Palbociclib plus endocrine therapy Endocrine therapy
    Number of subjects analysed
    2884
    2877
    Units: percent
        number (confidence interval 95%)
    84.2 (81.0 to 87.0)
    84.5 (81.4 to 87.2)
    Statistical analysis title
    Primary endpoint analysis
    Statistical analysis description
    Results were compared between treatment arms by Log-rank tests. Hazard ratios with 2-sided 95% CIs were calculated via stratified Cox proportional hazards regression models.
    Comparison groups
    Palbociclib plus endocrine therapy v Endocrine therapy
    Number of subjects included in analysis
    5761
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.65
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.81
         upper limit
    1.14

    Secondary: iBCFS

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    End point title
    iBCFS
    End point description
    Invasive breast cancer free survival (iBCFS) - hence, iDFS excluding second primary invasive cancers of non-breast origin - was defined as the time from randomization to the date of the first event (plus one day): local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence or death from any cause. Patients with second primary invasive cancers of non-breast origin will continue to be followed for iDFS. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, whichever occurs first. Survival rate estimates at 4 years with 2-sided 95% confidence intervals were calculated by Kaplan-Meier method.
    End point type
    Secondary
    End point timeframe
    Until the date of awareness of the 469th event
    End point values
    Palbociclib plus endocrine therapy Endocrine therapy
    Number of subjects analysed
    2884
    2877
    Units: percent
        number (confidence interval 95%)
    85.4 (82.1 to 88.1)
    86.0 (82.9 to 88.6)
    Statistical analysis title
    Secondary endpoint analysis - iBCFS
    Statistical analysis description
    Hazard ratios with 2-sided 95% CIs were calculated via stratified Cox proportional hazards regression models.
    Comparison groups
    Palbociclib plus endocrine therapy v Endocrine therapy
    Number of subjects included in analysis
    5761
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.82
         upper limit
    1.19

    Secondary: LRRFS

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    End point title
    LRRFS
    End point description
    Loco-regional recurrence free survival (LRRFS), was defined as the time from randomization to the date of the first event (plus one day): local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer or death from any cause. Patients with second primary invasive cancers of non-breast origin or distant recurrence were censored at the date of diagnosis. Surviving patients who were event-free were censored at: the date of last disease assessment, or withdrawal of consent to be followed, whichever occurs first. Survival rate estimates at 4 years with 2-sided 95% confidence intervals were calculated by Kaplan-Meier method.
    End point type
    Secondary
    End point timeframe
    Until the date of awareness of the 469th event
    End point values
    Palbociclib plus endocrine therapy Endocrine therapy
    Number of subjects analysed
    2884
    2877
    Units: percent
        number (confidence interval 95%)
    96.8 (94.4 to 98.2)
    95.4 (92.6 to 97.2)
    Statistical analysis title
    Secondary endpoint analysis - LRRFS
    Statistical analysis description
    Hazard ratios with 2-sided 95% CIs were calculated via stratified Cox proportional hazards regression models.
    Comparison groups
    Palbociclib plus endocrine therapy v Endocrine therapy
    Number of subjects included in analysis
    5761
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.57
         upper limit
    1.23

    Secondary: DRFS

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    End point title
    DRFS
    End point description
    Distant recurrence free survival (DRFS), was defined according to STEEP criteria as the time from randomization to the date of the first event: distant recurrence or death from any cause. Patients with a locoregional recurrence, contralateral invasive breast cancer or second primary invasive cancer of non-breast origin were continued to be followed for DRFS. Surviving patients who were event-free were censored at: the date of last disease assessment, or withdrawal of consent to be followed, whichever occurs first. Survival rate estimates at 4 years with 2-sided 95% confidence intervals were calculated by Kaplan-Meier method.
    End point type
    Secondary
    End point timeframe
    Until the date of awareness of the 469th event
    End point values
    Palbociclib plus endocrine therapy Endocrine therapy
    Number of subjects analysed
    2884
    2877
    Units: percent
        number (confidence interval 95%)
    86.2 (82.9 to 88.8)
    87.8 (84.9 to 90.2)
    Statistical analysis title
    Secondary endpoint analysis - DRFS
    Statistical analysis description
    Hazard ratios with 2-sided 95% CIs were calculated via stratified Cox proportional hazards regression models.
    Comparison groups
    Palbociclib plus endocrine therapy v Endocrine therapy
    Number of subjects included in analysis
    5761
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.87
         upper limit
    1.28

    Secondary: OS

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    End point title
    OS
    End point description
    Overall survival (OS), was defined according to STEEP criteria as the composite of: death from any cause. The time period between randomization and death from any cause was observed. Surviving patients who were event-free were censored at: the date of last contact (including patient’s status and patient’s end of study information) or withdrawal of consent to be followed, whichever occurs first. Survival rate estimates at 4 years with 2-sided 95% confidence intervals were calculated by Kaplan-Meier method.
    End point type
    Secondary
    End point timeframe
    Until the date of awareness of the 469th event
    End point values
    Palbociclib plus endocrine therapy Endocrine therapy
    Number of subjects analysed
    2884
    2877
    Units: percent
        number (confidence interval 95%)
    93.8 (91.9 to 95.3)
    95.2 (93.2 to 96.6)
    Statistical analysis title
    Secondary endpoint analysis - OS
    Statistical analysis description
    Hazard ratios with 2-sided 95% CIs were calculated via stratified Cox proportional hazards regression models.
    Comparison groups
    Palbociclib plus endocrine therapy v Endocrine therapy
    Number of subjects included in analysis
    5761
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.32
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.98
         upper limit
    1.78

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Start: date of informed consent form signature; End: 30 to 42 days after a patients' final treatment which is defined as the end of the Treatment Phase of the study. This would be approximately 2 years post-randomization, plus an additional 30-42 days.
    Adverse event reporting additional description
    Screening Phase: only AEs deemed to be serious (SAEs) and related to protocol mandated and not routinely performed procedures have to be reported; Follow up: SAEs deemed to be related to IP treatment have to be reported
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Palbociclib plus endocrine therapy
    Reporting group description
    -

    Reporting group title
    Endocrine therapy
    Reporting group description
    -

    Serious adverse events
    Palbociclib plus endocrine therapy Endocrine therapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    369 / 2841 (12.99%)
    229 / 2902 (7.89%)
         number of deaths (all causes)
    100
    76
         number of deaths resulting from adverse events
    14
    10
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
    Additional description: Acute myeloid leukaemia
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute promyelocytic leukaemia
    Additional description: Acute promyelocytic leukaemia
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma pancreas
    Additional description: Adenocarcinoma pancreas
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    B-cell small lymphocytic lymphoma
    Additional description: B-cell small lymphocytic lymphoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
    Additional description: Basal cell carcinoma
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign breast neoplasm
    Additional description: Benign breast neoplasm
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder neoplasm
    Additional description: Bladder neoplasm
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer metastatic
    Additional description: Breast cancer metastatic
         subjects affected / exposed
    2 / 2841 (0.07%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Breast cancer recurrent
    Additional description: Breast cancer recurrent
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cervix carcinoma
    Additional description: Cervix carcinoma
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervix carcinoma stage 0
    Additional description: Cervix carcinoma stage 0
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
    Additional description: Colon cancer
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial adenocarcinoma
    Additional description: Endometrial adenocarcinoma
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraductal papillary-mucinous carcinoma of pancreas
    Additional description: Intraductal papillary-mucinous carcinoma of pancreas
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm malignant
    Additional description: Lung neoplasm malignant
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphoma
    Additional description: Lymphoma
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphoplasmacytoid lymphoma/immunocytoma
    Additional description: Lymphoplasmacytoid lymphoma/immunocytoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
    Additional description: Malignant melanoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma in situ
    Additional description: Malignant melanoma in situ
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic malignant melanoma
    Additional description: Metastatic malignant melanoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian adenoma
    Additional description: Ovarian adenoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cell carcinoma
    Additional description: Renal cell carcinoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salivary gland adenoma
    Additional description: Salivary gland adenoma
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Second primary malignancy
    Additional description: Second primary malignancy
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Small cell carcinoma
    Additional description: Small cell carcinoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
    Additional description: Squamous cell carcinoma
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of the tongue
    Additional description: Squamous cell carcinoma of the tongue
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid adenoma
    Additional description: Thyroid adenoma
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
    Additional description: Uterine leiomyoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyosarcoma
    Additional description: Uterine leiomyosarcoma
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uveal melanoma
    Additional description: Uveal melanoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
    Additional description: Deep vein thrombosis
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Axillary vein thrombosis
    Additional description: Axillary vein thrombosis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism
    Additional description: Embolism
         subjects affected / exposed
    4 / 2841 (0.14%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
    Additional description: Hypertensive crisis
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
    Additional description: Hypotension
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphoedema
    Additional description: Lymphoedema
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
    Additional description: Peripheral ischaemia
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (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
    Additional description: Capsular contracture associated with breast implant
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest discomfort
    Additional description: Chest discomfort
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
    Additional description: Chest pain
         subjects affected / exposed
    3 / 2841 (0.11%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
    Additional description: Death
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Disease progression
    Additional description: Disease progression
         subjects affected / exposed
    1 / 2841 (0.04%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Disease recurrence
    Additional description: Disease recurrence
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Dysplasia
    Additional description: Dysplasia
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
    Additional description: Fatigue
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothermia
    Additional description: Hypothermia
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Impaired healing
    Additional description: Impaired healing
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Implant site fibrosis
    Additional description: Implant site fibrosis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza like illness
    Additional description: Influenza like illness
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion site extravasation
    Additional description: Infusion site extravasation
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
    Additional description: Non-cardiac chest pain
         subjects affected / exposed
    4 / 2841 (0.14%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
    Additional description: Pyrexia
         subjects affected / exposed
    3 / 2841 (0.11%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
    Additional description: Anaphylactic reaction
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Adnexa uteri cyst
    Additional description: Adnexa uteri cyst
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast calcifications
    Additional description: Breast calcifications
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cyst
    Additional description: Breast cyst
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast haematoma
    Additional description: Breast haematoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast necrosis
    Additional description: Breast necrosis
         subjects affected / exposed
    1 / 2841 (0.04%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast swelling
    Additional description: Breast swelling
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical cyst
    Additional description: Cervical cyst
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial disorder
    Additional description: Endometrial disorder
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial hyperplasia
    Additional description: Endometrial hyperplasia
         subjects affected / exposed
    1 / 2841 (0.04%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial hypertrophy
    Additional description: Endometrial hypertrophy
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial thickening
    Additional description: Endometrial thickening
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometriosis
    Additional description: Endometriosis
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst
    Additional description: Ovarian cyst
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine polyp
    Additional description: Uterine polyp
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine prolapse
    Additional description: Uterine prolapse
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haematoma
    Additional description: Vaginal haematoma
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal prolapse
    Additional description: Vaginal prolapse
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
    Additional description: Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
    Additional description: Asthma
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
    Additional description: Acute respiratory failure
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
    Additional description: Bronchospasm
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma-chronic obstructive pulmonary disease overlap syndrome
    Additional description: Asthma-chronic obstructive pulmonary disease overlap syndrome
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
    Additional description: Dyspnoea
         subjects affected / exposed
    2 / 2841 (0.07%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
    Additional description: Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
    Additional description: Hypoxia
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal stenosis
    Additional description: Laryngeal stenosis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
    Additional description: Pleurisy
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
    Additional description: Pleural effusion
         subjects affected / exposed
    2 / 2841 (0.07%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
    Additional description: Pulmonary embolism
         subjects affected / exposed
    13 / 2841 (0.46%)
    5 / 2902 (0.17%)
         occurrences causally related to treatment / all
    3 / 13
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
    Additional description: Pneumonitis
         subjects affected / exposed
    4 / 2841 (0.14%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary fibrosis
    Additional description: Pulmonary fibrosis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary haemorrhage
    Additional description: Pulmonary haemorrhage
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
    Additional description: Pulmonary oedema
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sarcoidosis
    Additional description: Pulmonary sarcoidosis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory disorder
    Additional description: Respiratory disorder
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
    Additional description: Respiratory failure
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vocal cord dysfunction
    Additional description: Vocal cord dysfunction
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vocal cord polyp
    Additional description: Vocal cord polyp
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol use disorder
    Additional description: Alcohol use disorder
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol abuse
    Additional description: Alcohol abuse
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol withdrawal syndrome
    Additional description: Alcohol withdrawal syndrome
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
    Additional description: Anxiety
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
    Additional description: Confusional state
         subjects affected / exposed
    3 / 2841 (0.11%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delusion
    Additional description: Delusion
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
    Additional description: Depression
         subjects affected / exposed
    3 / 2841 (0.11%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug abuse
    Additional description: Drug abuse
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mania
    Additional description: Mania
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental disorder
    Additional description: Mental disorder
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
    Additional description: Mental status changes
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Panic attack
    Additional description: Panic attack
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paranoia
    Additional description: Paranoia
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychotic disorder
    Additional description: Psychotic disorder
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
    Additional description: Suicidal ideation
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
    Additional description: Suicide attempt
         subjects affected / exposed
    0 / 2841 (0.00%)
    3 / 2902 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device breakage
    Additional description: Device breakage
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device dislocation
    Additional description: Device dislocation
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device leakage
    Additional description: Device leakage
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
    Additional description: Alanine aminotransferase increased
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
    Additional description: Blood bilirubin increased
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test increased
    Additional description: Liver function test increased
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
    Additional description: Neutrophil count decreased
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
    Additional description: Troponin increased
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
    Additional description: White blood cell count decreased
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence
    Additional description: Abdominal wound dehiscence
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol poisoning
    Additional description: Alcohol poisoning
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Animal bite
    Additional description: Animal bite
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
    Additional description: Ankle fracture
         subjects affected / exposed
    3 / 2841 (0.11%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain contusion
    Additional description: Brain contusion
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast procedural complication
    Additional description: Breast procedural complication
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
    Additional description: Clavicle fracture
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
    Additional description: Concussion
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
    Additional description: Craniocerebral injury
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
    Additional description: Fall
         subjects affected / exposed
    3 / 2841 (0.11%)
    3 / 2902 (0.10%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
    Additional description: Head injury
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
    Additional description: Hip fracture
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
    Additional description: Humerus fracture
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
    Additional description: Limb injury
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
    Additional description: Lower limb fracture
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
    Additional description: Meniscus injury
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Open fracture
    Additional description: Open fracture
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematoma
    Additional description: Post procedural haematoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound complication
    Additional description: Postoperative wound complication
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Procedural complication
    Additional description: Procedural complication
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation pneumonitis
    Additional description: Radiation pneumonitis
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
    Additional description: Radius fracture
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
    Additional description: Rib fracture
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
    Additional description: Seroma
         subjects affected / exposed
    3 / 2841 (0.11%)
    4 / 2902 (0.14%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin flap necrosis
    Additional description: Skin flap necrosis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
    Additional description: Spinal fracture
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sternal fracture
    Additional description: Sternal fracture
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
    Additional description: Subdural haematoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thermal burn
    Additional description: Thermal burn
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic vertebral fracture
    Additional description: Thoracic vertebral fracture
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
    Additional description: Upper limb fracture
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal cuff dehiscence
    Additional description: Vaginal cuff dehiscence
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular access site thrombosis
    Additional description: Vascular access site thrombosis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound complication
    Additional description: Wound complication
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound dehiscence
    Additional description: Wound dehiscence
         subjects affected / exposed
    9 / 2841 (0.32%)
    5 / 2902 (0.17%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
    Additional description: Wrist fracture
         subjects affected / exposed
    3 / 2841 (0.11%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Atrial septal defect
    Additional description: Atrial septal defect
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gene mutation
    Additional description: Gene mutation
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
    Additional description: Acute coronary syndrome
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
    Additional description: Acute myocardial infarction
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
    Additional description: Angina pectoris
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriospasm coronary
    Additional description: Arteriospasm coronary
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
    Additional description: Atrial fibrillation
         subjects affected / exposed
    2 / 2841 (0.07%)
    4 / 2902 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block
    Additional description: Atrioventricular block
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
    Additional description: Atrioventricular block complete
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
    Additional description: Cardiac arrest
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure
    Additional description: Cardiac failure
         subjects affected / exposed
    2 / 2841 (0.07%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure acute
    Additional description: Cardiac failure acute
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
    Additional description: Cardiac failure congestive
         subjects affected / exposed
    2 / 2841 (0.07%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac ventricular thrombosis
    Additional description: Cardiac ventricular thrombosis
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiomyopathy
    Additional description: Cardiomyopathy
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
    Additional description: Coronary artery disease
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Extrasystoles
    Additional description: Extrasystoles
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular failure
    Additional description: Left ventricular failure
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
    Additional description: Myocardial ischaemia
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Palpitations
    Additional description: Palpitations
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus bradycardia
    Additional description: Sinus bradycardia
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress cardiomyopathy
    Additional description: Stress cardiomyopathy
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
    Additional description: Supraventricular tachycardia
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Ageusia
    Additional description: Ageusia
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aphasia
    Additional description: Aphasia
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carpal tunnel syndrome
    Additional description: Carpal tunnel syndrome
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
    Additional description: Carotid artery stenosis
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
    Additional description: Cerebral infarction
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral ischaemia
    Additional description: Cerebral ischaemia
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
    Additional description: Dizziness
         subjects affected / exposed
    2 / 2841 (0.07%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
    Additional description: Cerebrovascular accident
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
    Additional description: Encephalopathy
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Facial paralysis
    Additional description: Facial paralysis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
    Additional description: Epilepsy
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
    Additional description: Headache
         subjects affected / exposed
    3 / 2841 (0.11%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
    Additional description: Haemorrhage intracranial
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    IIIrd nerve disorder
    Additional description: IIIrd nerve disorder
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intercostal neuralgia
    Additional description: Intercostal neuralgia
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
    Additional description: Ischaemic stroke
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myasthenia gravis
    Additional description: Myasthenia gravis
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
    Additional description: Paraesthesia
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
    Additional description: Presyncope
         subjects affected / exposed
    3 / 2841 (0.11%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ruptured cerebral aneurysm
    Additional description: Ruptured cerebral aneurysm
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Subarachnoid haemorrhage
    Additional description: Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
    Additional description: Syncope
         subjects affected / exposed
    2 / 2841 (0.07%)
    4 / 2902 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
    Additional description: Transient ischaemic attack
         subjects affected / exposed
    2 / 2841 (0.07%)
    3 / 2902 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VIth nerve paralysis
    Additional description: VIth nerve paralysis
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo CNS origin
    Additional description: Vertigo CNS origin
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
    Additional description: Anaemia
         subjects affected / exposed
    3 / 2841 (0.11%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia macrocytic
    Additional description: Anaemia macrocytic
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
    Additional description: Febrile neutropenia
         subjects affected / exposed
    13 / 2841 (0.46%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    13 / 13
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
    Additional description: Leukocytosis
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenitis
    Additional description: Lymphadenitis
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
    Additional description: Neutropenia
         subjects affected / exposed
    4 / 2841 (0.14%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
    Additional description: Pancytopenia
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic infarction
    Additional description: Splenic infarction
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness unilateral
    Additional description: Deafness unilateral
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo
    Additional description: Vertigo
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertigo positional
    Additional description: Vertigo positional
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
    Additional description: Cataract
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diplopia
    Additional description: Diplopia
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eyelid function disorder
    Additional description: Eyelid function disorder
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Maculopathy
    Additional description: Maculopathy
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
    Additional description: Abdominal hernia
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
    Additional description: Abdominal pain
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
    Additional description: Abdominal pain upper
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
    Additional description: Colitis ischaemic
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
    Additional description: Colitis
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
    Additional description: Diarrhoea
         subjects affected / exposed
    2 / 2841 (0.07%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
    Additional description: Duodenal ulcer
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
    Additional description: Duodenitis
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
    Additional description: Enteritis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
    Additional description: Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
    Additional description: Ileus
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
    Additional description: Intestinal obstruction
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal perforation
    Additional description: Intestinal perforation
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intussusception
    Additional description: Intussusception
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
    Additional description: Large intestine perforation
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
    Additional description: Large intestine polyp
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
    Additional description: Nausea
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic colitis
    Additional description: Neutropenic colitis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedematous pancreatitis
    Additional description: Oedematous pancreatitis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
    Additional description: Oesophagitis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
    Additional description: Pancreatitis
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal perforation
    Additional description: Peritoneal perforation
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
    Additional description: Small intestinal obstruction
         subjects affected / exposed
    2 / 2841 (0.07%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Volvulus of small bowel
    Additional description: Volvulus of small bowel
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
    Additional description: Vomiting
         subjects affected / exposed
    2 / 2841 (0.07%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Acute hepatic failure
    Additional description: Acute hepatic failure
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bile duct stone
    Additional description: Bile duct stone
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
    Additional description: Cholangitis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
    Additional description: Cholecystitis
         subjects affected / exposed
    3 / 2841 (0.11%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
    Additional description: Cholecystitis acute
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
    Additional description: Cholelithiasis
         subjects affected / exposed
    4 / 2841 (0.14%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-induced liver injury
    Additional description: Drug-induced liver injury
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
    Additional description: Hepatic failure
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatitis acute
    Additional description: Hepatitis acute
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Keloid scar
    Additional description: Keloid scar
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin necrosis
    Additional description: Skin necrosis
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria
    Additional description: Urticaria
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
    Additional description: Acute kidney injury
         subjects affected / exposed
    4 / 2841 (0.14%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
    Additional description: Chronic kidney disease
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
    Additional description: Nephrolithiasis
         subjects affected / exposed
    1 / 2841 (0.04%)
    4 / 2902 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
    Additional description: Renal colic
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcapsular renal haematoma
    Additional description: Subcapsular renal haematoma
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric obstruction
    Additional description: Ureteric obstruction
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric stenosis
    Additional description: Ureteric stenosis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
    Additional description: Ureterolithiasis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
    Additional description: Goitre
         subjects affected / exposed
    3 / 2841 (0.11%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperparathyroidism
    Additional description: Hyperparathyroidism
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypothyroidism
    Additional description: Hypothyroidism
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
    Additional description: Arthralgia
         subjects affected / exposed
    1 / 2841 (0.04%)
    4 / 2902 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
    Additional description: Arthritis
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
    Additional description: Back pain
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flank pain
    Additional description: Flank pain
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot deformity
    Additional description: Foot deformity
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemarthrosis
    Additional description: Haemarthrosis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
    Additional description: Intervertebral disc protrusion
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint range of motion decreased
    Additional description: Joint range of motion decreased
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
    Additional description: Osteoarthritis
         subjects affected / exposed
    1 / 2841 (0.04%)
    3 / 2902 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
    Additional description: Pain in extremity
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
    Additional description: Rotator cuff syndrome
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue necrosis
    Additional description: Soft tissue necrosis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal synovial cyst
    Additional description: Spinal synovial cyst
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendonitis
    Additional description: Tendonitis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
    Additional description: Anal abscess
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anorectal infection
    Additional description: Anorectal infection
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendiceal abscess
    Additional description: Appendiceal abscess
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
    Additional description: Appendicitis
         subjects affected / exposed
    3 / 2841 (0.11%)
    5 / 2902 (0.17%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis perforated
    Additional description: Appendicitis perforated
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial infection
    Additional description: Bacterial infection
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast abscess
    Additional description: Breast abscess
         subjects affected / exposed
    2 / 2841 (0.07%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cellulitis
    Additional description: Breast cellulitis
         subjects affected / exposed
    16 / 2841 (0.56%)
    10 / 2902 (0.34%)
         occurrences causally related to treatment / all
    7 / 17
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
    Additional description: Bronchitis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
    Additional description: COVID-19 pneumonia
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Campylobacter infection
    Additional description: Campylobacter infection
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
    Additional description: Cellulitis
         subjects affected / exposed
    24 / 2841 (0.84%)
    9 / 2902 (0.31%)
         occurrences causally related to treatment / all
    9 / 26
    0 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
    Additional description: Cystitis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (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
    Additional description: Device related infection
         subjects affected / exposed
    2 / 2841 (0.07%)
    4 / 2902 (0.14%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated varicella zoster virus infection
    Additional description: Disseminated varicella zoster virus infection
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
    Additional description: Diverticulitis
         subjects affected / exposed
    0 / 2841 (0.00%)
    3 / 2902 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
    Additional description: Erysipelas
         subjects affected / exposed
    5 / 2841 (0.18%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelothrix sepsis
    Additional description: Erysipelothrix sepsis
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia pyelonephritis
    Additional description: Escherichia pyelonephritis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
    Additional description: Escherichia sepsis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
    Additional description: Gastroenteritis
         subjects affected / exposed
    4 / 2841 (0.14%)
    3 / 2902 (0.10%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis norovirus
    Additional description: Gastroenteritis norovirus
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
    Additional description: Gastroenteritis viral
         subjects affected / exposed
    4 / 2841 (0.14%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
    Additional description: Herpes zoster
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected seroma
    Additional description: Infected seroma
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
    Additional description: Infection
         subjects affected / exposed
    2 / 2841 (0.07%)
    3 / 2902 (0.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
    Additional description: Influenza
         subjects affected / exposed
    16 / 2841 (0.56%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    3 / 16
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngitis
    Additional description: Laryngitis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Listeria sepsis
    Additional description: Listeria sepsis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Localised infection
    Additional description: Localised infection
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (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
    Additional description: Lower respiratory tract infection
         subjects affected / exposed
    2 / 2841 (0.07%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mastitis
    Additional description: Mastitis
         subjects affected / exposed
    13 / 2841 (0.46%)
    10 / 2902 (0.34%)
         occurrences causally related to treatment / all
    5 / 14
    0 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paronychia
    Additional description: Paronychia
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic inflammatory disease
    Additional description: Pelvic inflammatory disease
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
    Additional description: Peritonitis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
    Additional description: Pneumonia
         subjects affected / exposed
    16 / 2841 (0.56%)
    7 / 2902 (0.24%)
         occurrences causally related to treatment / all
    10 / 18
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Postoperative wound infection
    Additional description: Postoperative wound infection
         subjects affected / exposed
    1 / 2841 (0.04%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
    Additional description: Pyelonephritis
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
    Additional description: Pyelonephritis acute
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
    Additional description: Respiratory tract infection
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
    Additional description: Sepsis
         subjects affected / exposed
    8 / 2841 (0.28%)
    3 / 2902 (0.10%)
         occurrences causally related to treatment / all
    4 / 9
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
    Additional description: Septic shock
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
    Additional description: Sinusitis
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin infection
    Additional description: Skin infection
         subjects affected / exposed
    8 / 2841 (0.28%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    3 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Soft tissue infection
    Additional description: Soft tissue infection
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
    Additional description: Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
    Additional description: Staphylococcal infection
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
    Additional description: Upper respiratory tract infection
         subjects affected / exposed
    2 / 2841 (0.07%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
    Additional description: Urinary tract infection
         subjects affected / exposed
    8 / 2841 (0.28%)
    3 / 2902 (0.10%)
         occurrences causally related to treatment / all
    2 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
    Additional description: Urosepsis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular device infection
    Additional description: Vascular device infection
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular neuronitis
    Additional description: Vestibular neuronitis
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
    Additional description: Viral infection
         subjects affected / exposed
    4 / 2841 (0.14%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral labyrinthitis
    Additional description: Viral labyrinthitis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral pericarditis
    Additional description: Viral pericarditis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulvovaginal candidiasis
    Additional description: Vulvovaginal candidiasis
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound abscess
    Additional description: Wound abscess
         subjects affected / exposed
    2 / 2841 (0.07%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
    Additional description: Wound infection
         subjects affected / exposed
    3 / 2841 (0.11%)
    4 / 2902 (0.14%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
    Additional description: Dehydration
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
    Additional description: Hypercalcaemia
         subjects affected / exposed
    1 / 2841 (0.04%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypoglycaemia
    Additional description: Hypoglycaemia
         subjects affected / exposed
    1 / 2841 (0.04%)
    0 / 2902 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
    Additional description: Hypokalaemia
         subjects affected / exposed
    0 / 2841 (0.00%)
    1 / 2902 (0.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
    Additional description: Hyponatraemia
         subjects affected / exposed
    0 / 2841 (0.00%)
    2 / 2902 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Palbociclib plus endocrine therapy Endocrine therapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2824 / 2841 (99.40%)
    2600 / 2902 (89.59%)
    Vascular disorders
    Hot flush
    Additional description: Hot flush
         subjects affected / exposed
    703 / 2841 (24.74%)
    849 / 2902 (29.26%)
         occurrences all number
    888
    1066
    Hypertension
    Additional description: Hypertension
         subjects affected / exposed
    205 / 2841 (7.22%)
    227 / 2902 (7.82%)
         occurrences all number
    363
    382
    Lymphoedema
    Additional description: Lymphoedema
         subjects affected / exposed
    337 / 2841 (11.86%)
    268 / 2902 (9.24%)
         occurrences all number
    396
    303
    General disorders and administration site conditions
    Asthenia
    Additional description: Asthenia
         subjects affected / exposed
    274 / 2841 (9.64%)
    153 / 2902 (5.27%)
         occurrences all number
    468
    193
    Fatigue
    Additional description: Fatigue
         subjects affected / exposed
    1163 / 2841 (40.94%)
    560 / 2902 (19.30%)
         occurrences all number
    1869
    714
    Influenza like illness
    Additional description: Influenza like illness
         subjects affected / exposed
    166 / 2841 (5.84%)
    90 / 2902 (3.10%)
         occurrences all number
    205
    108
    Mucosal inflammation
    Additional description: Mucosal inflammation
         subjects affected / exposed
    206 / 2841 (7.25%)
    10 / 2902 (0.34%)
         occurrences all number
    362
    10
    Oedema peripheral
    Additional description: Oedema peripheral
         subjects affected / exposed
    178 / 2841 (6.27%)
    121 / 2902 (4.17%)
         occurrences all number
    218
    137
    Pyrexia
    Additional description: Pyrexia
         subjects affected / exposed
    205 / 2841 (7.22%)
    83 / 2902 (2.86%)
         occurrences all number
    251
    92
    Reproductive system and breast disorders
    Breast pain
    Additional description: Breast pain
         subjects affected / exposed
    145 / 2841 (5.10%)
    158 / 2902 (5.44%)
         occurrences all number
    163
    186
    Vulvovaginal dryness
    Additional description: Vulvovaginal dryness
         subjects affected / exposed
    182 / 2841 (6.41%)
    213 / 2902 (7.34%)
         occurrences all number
    211
    254
    Respiratory, thoracic and mediastinal disorders
    Cough
    Additional description: Cough
         subjects affected / exposed
    416 / 2841 (14.64%)
    222 / 2902 (7.65%)
         occurrences all number
    543
    256
    Dyspnoea
    Additional description: Dyspnoea
         subjects affected / exposed
    197 / 2841 (6.93%)
    130 / 2902 (4.48%)
         occurrences all number
    247
    144
    Oropharyngeal pain
    Additional description: Oropharyngeal pain
         subjects affected / exposed
    155 / 2841 (5.46%)
    60 / 2902 (2.07%)
         occurrences all number
    169
    65
    Psychiatric disorders
    Anxiety
    Additional description: Anxiety
         subjects affected / exposed
    157 / 2841 (5.53%)
    143 / 2902 (4.93%)
         occurrences all number
    184
    168
    Depression
    Additional description: Depression
         subjects affected / exposed
    156 / 2841 (5.49%)
    150 / 2902 (5.17%)
         occurrences all number
    191
    175
    Insomnia
    Additional description: Insomnia
         subjects affected / exposed
    383 / 2841 (13.48%)
    357 / 2902 (12.30%)
         occurrences all number
    468
    418
    Investigations
    Aspartate aminotransferase increased
    Additional description: Aspartate aminotransferase increased
         subjects affected / exposed
    210 / 2841 (7.39%)
    114 / 2902 (3.93%)
         occurrences all number
    288
    151
    Alanine aminotransferase increased
    Additional description: Alanine aminotransferase increased
         subjects affected / exposed
    212 / 2841 (7.46%)
    138 / 2902 (4.76%)
         occurrences all number
    345
    175
    Lymphocyte count decreased
    Additional description: Lymphocyte count decreased
         subjects affected / exposed
    317 / 2841 (11.16%)
    100 / 2902 (3.45%)
         occurrences all number
    926
    161
    Neutrophil count decreased
    Additional description: Neutrophil count decreased
         subjects affected / exposed
    1344 / 2841 (47.31%)
    67 / 2902 (2.31%)
         occurrences all number
    6144
    109
    Platelet count decreased
    Additional description: Platelet count decreased
         subjects affected / exposed
    436 / 2841 (15.35%)
    35 / 2902 (1.21%)
         occurrences all number
    850
    50
    White blood cell count decreased
    Additional description: White blood cell count decreased
         subjects affected / exposed
    1187 / 2841 (41.78%)
    155 / 2902 (5.34%)
         occurrences all number
    5122
    242
    Nervous system disorders
    Headache
    Additional description: Headache
         subjects affected / exposed
    445 / 2841 (15.66%)
    338 / 2902 (11.65%)
         occurrences all number
    590
    405
    Dizziness
    Additional description: Dizziness
         subjects affected / exposed
    248 / 2841 (8.73%)
    169 / 2902 (5.82%)
         occurrences all number
    306
    190
    Neuropathy peripheral
    Additional description: Neuropathy peripheral
         subjects affected / exposed
    148 / 2841 (5.21%)
    102 / 2902 (3.51%)
         occurrences all number
    186
    121
    Blood and lymphatic system disorders
    Anaemia
    Additional description: Anaemia
         subjects affected / exposed
    634 / 2841 (22.32%)
    147 / 2902 (5.07%)
         occurrences all number
    1161
    211
    Neutropenia
    Additional description: Neutropenia
         subjects affected / exposed
    1126 / 2841 (39.63%)
    76 / 2902 (2.62%)
         occurrences all number
    5383
    112
    Leukopenia
    Additional description: Leukopenia
         subjects affected / exposed
    397 / 2841 (13.97%)
    64 / 2902 (2.21%)
         occurrences all number
    1798
    98
    Thrombocytopenia
    Additional description: Thrombocytopenia
         subjects affected / exposed
    195 / 2841 (6.86%)
    15 / 2902 (0.52%)
         occurrences all number
    403
    18
    Gastrointestinal disorders
    Abdominal pain
    Additional description: Abdominal pain
         subjects affected / exposed
    153 / 2841 (5.39%)
    110 / 2902 (3.79%)
         occurrences all number
    190
    134
    Constipation
    Additional description: Constipation
         subjects affected / exposed
    395 / 2841 (13.90%)
    172 / 2902 (5.93%)
         occurrences all number
    485
    190
    Nausea
    Additional description: Nausea
         subjects affected / exposed
    552 / 2841 (19.43%)
    241 / 2902 (8.30%)
         occurrences all number
    735
    294
    Diarrhoea
    Additional description: Diarrhoea
         subjects affected / exposed
    475 / 2841 (16.72%)
    150 / 2902 (5.17%)
         occurrences all number
    682
    194
    Vomiting
    Additional description: Vomiting
         subjects affected / exposed
    219 / 2841 (7.71%)
    91 / 2902 (3.14%)
         occurrences all number
    278
    120
    Stomatitis
    Additional description: Stomatitis
         subjects affected / exposed
    280 / 2841 (9.86%)
    21 / 2902 (0.72%)
         occurrences all number
    428
    23
    Skin and subcutaneous tissue disorders
    Alopecia
    Additional description: Alopecia
         subjects affected / exposed
    511 / 2841 (17.99%)
    149 / 2902 (5.13%)
         occurrences all number
    559
    163
    Dry skin
    Additional description: Dry skin
         subjects affected / exposed
    153 / 2841 (5.39%)
    56 / 2902 (1.93%)
         occurrences all number
    178
    67
    Pruritus
    Additional description: Pruritus
         subjects affected / exposed
    183 / 2841 (6.44%)
    95 / 2902 (3.27%)
         occurrences all number
    222
    105
    Rash
    Additional description: Rash
         subjects affected / exposed
    229 / 2841 (8.06%)
    90 / 2902 (3.10%)
         occurrences all number
    288
    102
    Musculoskeletal and connective tissue disorders
    Arthralgia
    Additional description: Arthralgia
         subjects affected / exposed
    1087 / 2841 (38.26%)
    1305 / 2902 (44.97%)
         occurrences all number
    1650
    2034
    Back pain
    Additional description: Back pain
         subjects affected / exposed
    311 / 2841 (10.95%)
    287 / 2902 (9.89%)
         occurrences all number
    369
    346
    Muscle spasms
    Additional description: Muscle spasms
         subjects affected / exposed
    193 / 2841 (6.79%)
    124 / 2902 (4.27%)
         occurrences all number
    229
    131
    Myalgia
    Additional description: Myalgia
         subjects affected / exposed
    250 / 2841 (8.80%)
    235 / 2902 (8.10%)
         occurrences all number
    315
    276
    Pain in extremity
    Additional description: Pain in extremity
         subjects affected / exposed
    265 / 2841 (9.33%)
    280 / 2902 (9.65%)
         occurrences all number
    346
    349
    Infections and infestations
    Nasopharyngitis
    Additional description: Nasopharyngitis
         subjects affected / exposed
    210 / 2841 (7.39%)
    127 / 2902 (4.38%)
         occurrences all number
    275
    157
    Upper respiratory tract infection
    Additional description: Upper respiratory tract infection
         subjects affected / exposed
    304 / 2841 (10.70%)
    185 / 2902 (6.37%)
         occurrences all number
    390
    229
    Urinary tract infection
    Additional description: Urinary tract infection
         subjects affected / exposed
    234 / 2841 (8.24%)
    145 / 2902 (5.00%)
         occurrences all number
    320
    204
    Metabolism and nutrition disorders
    Decreased appetite
    Additional description: Decreased appetite
         subjects affected / exposed
    151 / 2841 (5.32%)
    73 / 2902 (2.52%)
         occurrences all number
    176
    87

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Aug 2015
    Updates to clarifiy endpoints, analyses and concomitant medication. Updated description of recurrences, duration of disease monitoring and diagnosis. Adminisatrative updates and wordsmithing.
    04 Apr 2018
    Sample size increase, updates to timepoints of sample collection and in regards to updated IB. Updates to clarify eligibility criteria, administrative updates and wordsmithing.
    23 Dec 2020
    Updates to implement results of second interim analysis, measures during COVID-19 pandemic to safeguard patient safety and data integrity and additional biosample collection 7 and 10 years post-randomization. Updates to clarify statistical endpoints, administrative changes and wordsmithing.

    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.
    Limitation of an unblinded design.

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/33460574
    For support, Contact us.
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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