Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44364   clinical trials with a EudraCT protocol, of which   7388   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase III Prospective, Two-Cohort Non-Randomized, Multi-Centre, Multinational, Open-Label Study to Assess the Safety of Assisted- and Self-Administered Subcutaneous Trastuzumab as Therapy in Patients With Operable HER2-Positive Early Breast Cancer (SafeHER)

    Summary
    EudraCT number
    		 2011-005328-17
    Trial protocol
    		 IE   CZ   DE   ES   FR   HU   PT   GB   NO   IT   GR   LT   PL   SI   SK   FI   BG   NL   SE  
    Global end of trial date
    19 Feb 2020

    Results information
    Results version number
    		 v2(current)
    This version publication date
    04 Mar 2021
    First version publication date
    22 Mar 2017
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MO28048
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01566721
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann- La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
    Scientific contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Jun 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Feb 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This multicenter, two-cohort, non-randomized, open-label study is designed to evaluate the safety and tolerability of assisted and self-administered subcutaneous (SC) Herceptin (trastuzumab) as adjuvant therapy in subjects with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer following tumor excision.
    Protection of trial subjects
    The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP) guidelines according to the regulations and procedures described in the protocol.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 May 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy, Safety
    Long term follow-up duration
    		 6 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Albania: 8
    Country: Number of subjects enrolled
    Algeria: 16
    Country: Number of subjects enrolled
    Argentina: 13
    Country: Number of subjects enrolled
    Australia: 54
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 5
    Country: Number of subjects enrolled
    Brazil: 31
    Country: Number of subjects enrolled
    Bulgaria: 16
    Country: Number of subjects enrolled
    Canada: 50
    Country: Number of subjects enrolled
    Chile: 25
    Country: Number of subjects enrolled
    Colombia: 6
    Country: Number of subjects enrolled
    Croatia: 7
    Country: Number of subjects enrolled
    Czechia: 68
    Country: Number of subjects enrolled
    Dominican Republic: 2
    Country: Number of subjects enrolled
    Ecuador: 13
    Country: Number of subjects enrolled
    Egypt: 34
    Country: Number of subjects enrolled
    El Salvador: 6
    Country: Number of subjects enrolled
    France: 224
    Country: Number of subjects enrolled
    Germany: 235
    Country: Number of subjects enrolled
    Greece: 64
    Country: Number of subjects enrolled
    Guatemala: 16
    Country: Number of subjects enrolled
    Hong Kong: 10
    Country: Number of subjects enrolled
    Hungary: 39
    Country: Number of subjects enrolled
    Indonesia: 61
    Country: Number of subjects enrolled
    Ireland: 26
    Country: Number of subjects enrolled
    Italy: 203
    Country: Number of subjects enrolled
    Korea, Republic of: 59
    Country: Number of subjects enrolled
    Lithuania: 12
    Country: Number of subjects enrolled
    Malaysia: 45
    Country: Number of subjects enrolled
    Mexico: 52
    Country: Number of subjects enrolled
    Morocco: 8
    Country: Number of subjects enrolled
    Netherlands: 81
    Country: Number of subjects enrolled
    New Zealand: 10
    Country: Number of subjects enrolled
    Norway: 29
    Country: Number of subjects enrolled
    Pakistan: 46
    Country: Number of subjects enrolled
    Panama: 8
    Country: Number of subjects enrolled
    Peru: 26
    Country: Number of subjects enrolled
    Philippines: 48
    Country: Number of subjects enrolled
    Poland: 48
    Country: Number of subjects enrolled
    Portugal: 26
    Country: Number of subjects enrolled
    Romania: 43
    Country: Number of subjects enrolled
    Russian Federation: 82
    Country: Number of subjects enrolled
    Saudi Arabia: 3
    Country: Number of subjects enrolled
    Serbia: 23
    Country: Number of subjects enrolled
    Singapore: 8
    Country: Number of subjects enrolled
    Slovakia: 19
    Country: Number of subjects enrolled
    Slovenia: 5
    Country: Number of subjects enrolled
    South Africa: 17
    Country: Number of subjects enrolled
    Spain: 161
    Country: Number of subjects enrolled
    Sweden: 15
    Country: Number of subjects enrolled
    Switzerland: 40
    Country: Number of subjects enrolled
    Taiwan: 32
    Country: Number of subjects enrolled
    Thailand: 28
    Country: Number of subjects enrolled
    Turkey: 47
    Country: Number of subjects enrolled
    Ukraine: 17
    Country: Number of subjects enrolled
    United Arab Emirates: 5
    Country: Number of subjects enrolled
    United Kingdom: 283
    Country: Number of subjects enrolled
    Uruguay: 3
    Country: Number of subjects enrolled
    Venezuela, Bolivarian Republic of: 5
    Country: Number of subjects enrolled
    Vietnam: 11
    Worldwide total number of subjects
    2577
    EEA total number of subjects
    1321
    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)
    2090
    From 65 to 84 years
    483
    85 years and over
    4

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 In this international study, 2577 subjects were enrolled at 49 academic centers throughout North America, Europe, the Middle East, and South America.

    Pre-assignment
    Screening details
    		 Of the 2984 subjects screened, a total of 2577 subjects were enrolled into the trial, and 2573 subjects received at least one dose of study treatment. 4 Subjects were not included in the Safety Follow-Up (SFU) ITT due to the lack of Principal Investigator signatures.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    From Baseline to Safety Follow-up Period (Up to 6 Years)

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort A: SC Herceptin by Needle/Syringe
    Arm description
    		 Subjects received SC Herceptin by an assisted administration as 600 milligrams (mg) every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Herceptin
    Investigational medicinal product code
    Other name
    Trastuzumab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Herceptin was given as 600 mg SC (into thigh) on Day 1 of each 3-week cycle for up to 18 cycles. Safety Follow-up Period up to approximately 6 years.

    Arm title
    		 Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Arm description
    		 Subjects received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by a healthcare professional (HCP). Subsequent doses were self-administered by subjects who were willing and judged competent by the HCP.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Herceptin
    Investigational medicinal product code
    Other name
    Trastuzumab
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Herceptin was given as 600 mg SC (into thigh) on Day 1 of each 3-week cycle for up to 18 cycles. Safety Follow-up Period, up to approximately 6 years.

    Number of subjects in period 1
    		Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Started
    1867
    710
    Completed Treatment (ITT)
    1670
    652
    Started Safety Follow-up (ITT)
    1865
    708
    Completed
    1318
    501
    Not completed
    549
    209
         Physician decision
    6
    4
         Disease progression /disease recurrence
    223
    90
         Erroneous reporting or late reporting
    2
    -
         Sponsor decision
    1
    -
         Missing
    7
    2
         Site closure
    2
    3
         Consent withdrawn by subject
    155
    49
         Adverse event, non-fatal
    8
    4
         Death
    28
    4
         Non-compliance
    7
    3
         Lost to follow-up
    101
    48
         Investigator signature missing
    2
    2
         Protocol deviation
    7
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort A: SC Herceptin by Needle/Syringe
    Reporting group description
    		 Subjects received SC Herceptin by an assisted administration as 600 milligrams (mg) every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe.

    Reporting group title
    Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Reporting group description
    		 Subjects received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by a healthcare professional (HCP). Subsequent doses were self-administered by subjects who were willing and judged competent by the HCP.

    Reporting group values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID) Total
    Number of subjects
    		 1867 710
    Age categorical
    From total 2577 subjects, 4 subjects did not receive the study treatment, therefore 2573 subjects were included Baseline Characteristics.
    Units: Years
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 54 ( 12.01 ) 53 ( 11.32 ) -
    Gender categorical
    Units: Subjects
        Female
    		 1863 710 2573
        Male
    		 4 0 4

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cohort A: SC Herceptin by Needle/Syringe
    Reporting group description
    		 Subjects received SC Herceptin by an assisted administration as 600 milligrams (mg) every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe.

    Reporting group title
    Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Reporting group description
    		 Subjects received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by a healthcare professional (HCP). Subsequent doses were self-administered by subjects who were willing and judged competent by the HCP.

    Primary: Percentage of Subjects With At Least 1 Adverse Event (AE) During the Treatment Period

    		 Close Top of page
    End point title
    		 Percentage of Subjects With At Least 1 Adverse Event (AE) During the Treatment Period [1]
    End point description
    Subjects were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a subjects administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. The percentage of subjects with at least 1 AE during the treatment period (regardless of severity or seriousness) was reported. Safety Population: All enrolled subjects who received at least one dose of study medication according to assigned treatment.
    End point type
    Primary
    End point timeframe
    From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    1864
    709
    Units: Percentage of Subjects
        number (not applicable)
    88.6
    89
    No statistical analyses for this end point

    Primary: Percentage of Subjects With a Grade 3 or Higher AE During the Treatment Period

    		 Close Top of page
    End point title
    		 Percentage of Subjects With a Grade 3 or Higher AE During the Treatment Period [2]
    End point description
    Subjects were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a subject administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. AEs were graded according to National Cancer Institute Common Terminology Criteria Version 4.0. Grade 3 AEs were those considered severe or medically significant but not immediately life-threatening. Grade 4 AEs were those considered life-threatening and/or for which urgent intervention was indicated. Grade 5 AEs were those resulting in death. The percentage of subjects with a Grade 3 or higher (i.e., Grade 3 to 5) AE during the treatment period was reported. Safety Population.
    End point type
    Primary
    End point timeframe
    From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    1864
    709
    Units: Percentage of Subjects
        number (confidence interval 95%)
    24 (22.1 to 26)
    21 (18.1 to 24.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Treatment Interruption Due to an AE

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Treatment Interruption Due to an AE [3]
    End point description
    Subjects were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. The percentage of subjects with SC Herceptin treatment interrupted to assess or treat AEs was reported. Safety Population.
    End point type
    Primary
    End point timeframe
    From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    1864
    709
    Units: Percentage of Subjects
        number (not applicable)
    9.8
    10.4
    No statistical analyses for this end point

    Primary: Number of Herceptin Cycles Received

    		 Close Top of page
    End point title
    		 Number of Herceptin Cycles Received [4]
    End point description
    Participants were planned to receive a total of 18 cycles of SC Herceptin. The median number of cycles actually received was reported. Safety Population. The endpoint also included an analysis of a subgroup of participants from Cohort B who received doses of self-administered SC Herceptin via SID.
    End point type
    Primary
    End point timeframe
    From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    1864
    709
    Units: cycles
        median (full range (min-max))
    18 (1 to 19)
    18 (1 to 18)
    No statistical analyses for this end point

    Primary: Percentage of Subjects by Total Number of Herceptin Cycles Received

    		 Close Top of page
    End point title
    		 Percentage of Subjects by Total Number of Herceptin Cycles Received [5]
    End point description
    Participants were planned to receive a total of 18 cycles of SC Herceptin. The percentage of subjects was reported by the total number of cycles actually received. Because the data are presented non-cumulatively, this table reflects subjects distribution by the highest number of cycles received. Safety Population. The endpoint also included an analysis of a subgroup of subjects from Cohort B who received doses of self-administered SC Herceptin via SID.
    End point type
    Primary
    End point timeframe
    From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    1864
    709
    Units: Percentage of Subjects
    number (not applicable)
        1 Cycle Received
    1
    0.8
        2 Cycles Received
    0.5
    0.4
        3 Cycles Received
    0.5
    0.1
        4 Cycles Received
    1.2
    0.7
        5 Cycles Received
    0.8
    0.6
        6 Cycles Received
    0.5
    0.1
        7 Cycles Received
    0.7
    0.8
        8 Cycles Received
    0.9
    0.3
        9 Cycles Received
    0.2
    0.6
        10 Cycles Received
    0.3
    0.1
        11 Cycles Received
    0.4
    0.3
        12 Cycles Received
    0.9
    0.8
        13 Cycles Received
    0.2
    0
        14 Cycles Received
    0.5
    0.6
        15 Cycles Received
    0.5
    0.4
        16 Cycles Received
    0.6
    0.3
        17 Cycles Received
    1
    1.1
        18 Cycles Received
    89.2
    91.8
        19 Cycles Received
    0.2
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects Who Received Concomitant Cancer Therapy

    		 Close Top of page
    End point title
    		 Percentage of Subjects Who Received Concomitant Cancer Therapy [6]
    End point description
    Concomitant cancer treatment included chemotherapy, radiotherapy, and hormone therapy administered during the study. The percentage of subjects who received any of these concomitant therapies was reported. Safety Population.
    End point type
    Primary
    End point timeframe
    From Baseline to data cutoff of 10 March 2015 (up to approximately 3 years)
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    1864
    709
    Units: Percentage of Subjects
    number (not applicable)
        Chemotherapy
    63.9
    58.2
        Radiotherapy
    48.5
    51.3
        Hormone Therapy
    50.4
    51.3
    No statistical analyses for this end point

    Primary: Percentage of Subjects Who Received Concomitant Non-Cancer Therapy

    		 Close Top of page
    End point title
    		 Percentage of Subjects Who Received Concomitant Non-Cancer Therapy [7]
    End point description
    Concomitant non-cancer treatment included any pharmacologic interventions administered during the study other than chemotherapy, radiotherapy, or hormone therapy. The percentage of subjects who received any concomitant non-cancer therapies was reported. Safety Population.
    End point type
    Primary
    End point timeframe
    From Baseline to data cutoff of 10 March 2015 (up to approximately 3 years)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics was planned to be reported in the endpoint.
    End point values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    1864
    709
    Units: Percentage of Subjects
        number (not applicable)
    89.1
    89.7
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Died by Data Cutoff of 10 March 2015

    		 Close Top of page
    End point title
    		 Percentage of Subjects Who Died by Data Cutoff of 10 March 2015
    End point description
    The subjects of subjects who died from any cause was reported. ITT Population: All subjects enrolled into the study regardless of whether treatment was received.
    End point type
    Secondary
    End point timeframe
    From Baseline to time of event (maximum follow-up approximately 3 years as of data cutoff of 10 March 2015)
    End point values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    1864
    709
    Units: Percentage of Subjects
        number (not applicable)
    1.5
    0.8
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Died from Baseline to Safety Follow-up Period

    		 Close Top of page
    End point title
    		 Percentage of Subjects Who Died from Baseline to Safety Follow-up Period
    End point description
    The percentage of subjects who died from any cause was reported. ITT Population: All subjects enrolled into the study regardless of whether treatment was received. 4 Subjects were not included in the final analyses due to the lack of Principal Investigator signatures in the subjects specific casebooks.
    End point type
    Secondary
    End point timeframe
    Safety Follow-up period, up to approximately 6 years
    End point values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    1865
    708
    Units: Percentage of Subjects
        number (not applicable)
    6.8
    7.3
    No statistical analyses for this end point

    Secondary: Percentage of Subjects by Item Response to SID Satisfaction Questionnaire

    		 Close Top of page
    End point title
    		 Percentage of Subjects by Item Response to SID Satisfaction Questionnaire [8]
    End point description
    The SID satisfaction questionnaire was administered twice during study and asked subjects to respond to five statements using a Likert scale from "Strongly Disagree" to "Strongly Agree". Questionnaire items were: "I felt comfortable injecting the study drug by myself" (Comfortable), "The SID was convenient and easy to use" (Easy to Use), "I am confident giving myself an injection in the thigh with the SID" (Confident), "Taking all things into account I find self-administration using the SID satisfactory" (Satisfactory), "If given the opportunity I would choose to continue self-injecting the study drug using the SID in the future" (Continue). Subjects could select one response per questionnaire item. The percentage of subjects was reported by response given for each item on the SID satisfaction questionnaire. Safety Population. Only those who self-administered were included. The number of subjects who responded to the questionnaire item at each assessment (n) is shown.
    End point type
    Secondary
    End point timeframe
    Cycle 4 (cycle length 3 weeks) and last safety follow-up (LSFU) (approximately 1 year)
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was provided only for those arms which were planned to be reported.
    End point values
    		 Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    709
    Units: Percentage of Subjects
    number (not applicable)
        Cycle 4: Comfortable, Strongly Disagree (n=514)
    4.7
        Cycle 4: Comfortable, Disagree (n=514)
    2.3
        Cycle 4: Comfortable, Unsure (n=514)
    4.6
        Cycle 4: Comfortable, Agree (n=514)
    41.6
        Cycle 4: Comfortable, Strongly Agree (n=514)
    43.6
        Cycle 4: Comfortable, Response Missing (n=514)
    0.2
        Cycle 4: Easy to Use, Strongly Disagree (n=514)
    3.7
        Cycle 4: Easy to Use, Disagree (n=514)
    0.6
        Cycle 4: Easy to Use, Unsure (n=514)
    1.8
        Cycle 4: Easy to Use, Agree (n=514)
    37.7
        Cycle 4: Easy to Use, Strongly Agree (n=514)
    56
        Cycle 4: Easy to Use, Response Missing (n=514)
    0.2
        Cycle 4: Confident, Strongly Disagree (n=514)
    3.9
        Cycle 4: Confident, Disagree (n=514)
    0.8
        Cycle 4: Confident, Unsure (n=514)
    7.2
        Cycle 4: Confident, Agree (n=514)
    42.8
        Cycle 4: Confident, Strongly Agree (n=514)
    45.1
        Cycle 4: Confident, Response Missing (n=514)
    0.2
        Cycle 4: Satisfactory, Strongly Disagree (n=514)
    3.9
        Cycle 4: Satisfactory, Disagree (n=514)
    0.6
        Cycle 4: Satisfactory, Unsure (n=514)
    2.7
        Cycle 4: Satisfactory, Agree (n=514)
    38.7
        Cycle 4: Satisfactory, Strongly Agree (n=514)
    53.9
        Cycle 4: Satisfactory, Response Missing (n=514)
    0.2
        Cycle 4: Continue, Strongly Disagree (n=514)
    3.9
        Cycle 4: Continue, Disagree (n=514)
    1.4
        Cycle 4: Continue, Unsure (n=514)
    5.3
        Cycle 4: Continue, Agree (n=514)
    33.5
        Cycle 4: Continue, Strongly Agree (n=514)
    55.8
        Cycle 4: Continue, Response Missing (n=514)
    0.2
        LSFU: Comfortable, Strongly Disagree (n=415)
    3.6
        LSFU: Comfortable, Disagree (n=415)
    3.1
        LSFU: Comfortable, Unsure (n=415)
    5.3
        LSFU: Comfortable, Agree (n=415)
    35.9
        LSFU: Comfortable, Strongly Agree (n=415)
    51.8
        LSFU: Comfortable, Response Missing (n=415)
    0.2
        LSFU: Easy to Use, Strongly Disagree (n=415)
    3.9
        LSFU: Easy to Use, Disagree (n=415)
    1
        LSFU: Easy to Use, Unsure (n=415)
    1.7
        LSFU: Easy to Use, Agree (n=415)
    34.9
        LSFU: Easy to Use, Strongly Agree (n=415)
    58.6
        LSFU: Easy to Use, Response Missing (n=415)
    0
        LSFU: Confident, Strongly Disagree (n=415)
    4.6
        LSFU: Confident, Disagree (n=415)
    1.2
        LSFU: Confident, Unsure (n=415)
    4.3
        LSFU: Confident, Agree (n=415)
    33.3
        LSFU: Confident, Strongly Agree (n=415)
    56.6
        LSFU: Confident, Response Missing (n=415)
    0
        LSFU: Satisfactory, Strongly Disagree (n=415)
    4.3
        LSFU: Satisfactory, Disagree (n=415)
    1.2
        LSFU: Satisfactory, Unsure (n=415)
    2.2
        LSFU: Satisfactory, Agree (n=415)
    30.8
        LSFU: Satisfactory, Strongly Agree (n=415)
    61.2
        LSFU: Satisfactory, Response Missing (n=415)
    0.2
        LSFU: Continue, Strongly Disagree (n=415)
    4.6
        LSFU: Continue, Disagree (n=415)
    1.2
        LSFU: Continue, Unsure (n=415)
    2.9
        LSFU: Continue, Agree (n=415)
    28.2
        LSFU: Continue, Strongly Agree (n=415)
    63.1
        LSFU: Continue, Response Missing (n=415)
    0
    No statistical analyses for this end point

    Secondary: Disease Free Survival Rate

    		 Close Top of page
    End point title
    		 Disease Free Survival Rate
    End point description
    ITT population in SFU, 4 Participants were not included in the final analyses due to the lack of Principal Investigator signatures in the participant specific casebooks.
    End point type
    Secondary
    End point timeframe
    From Baseline to Time of Event (Up to Approximately 6 Years)
    End point values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    1865
    708
    Units: Ratio
    number (confidence interval 95%)
        0.5 Year
    0.990 (0.984 to 0.993)
    0.987 (0.976 to 0.993)
        1 Year
    0.975 (0.967 to 0.981)
    0.976 (0.961 to 0.98)
        1.5 Year
    0.960 (0.950 to 0.968)
    0.957 (0.939 to 0.970)
        2 Years
    0.934 (0.921 to 0.944)
    0.939 (0.918 to 0.955)
        3 Years
    0.904 (0.889 to 0.917)
    0.896 (0.870 to 0.916)
        4 Years
    0.881 (0.865 to 0.896)
    0.874 (0.847 to 0.897)
        5 Years
    0.868 (0.851 to 0.883)
    0.863 (0.835 to 0.887)
        6 Years
    0.851 (0.833 to 0.867)
    0.853 (0.824 to 0.878)
    No statistical analyses for this end point

    Secondary: Overall Survival Rate

    		 Close Top of page
    End point title
    		 Overall Survival Rate
    End point description
    ITT Population. 4 Participants were not included in the final analyses due to the lack of Principal Investigator signatures in the participant specific casebooks.
    End point type
    Secondary
    End point timeframe
    From Baseline to Time of Event (Up to Approximately 6 Years)
    End point values
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Number of subjects analysed
    1865
    708
    Units: Ratio
    number (confidence interval 95%)
        0.5 Year
    0.999 (0.996 to 1.000)
    0.996 (0.987 to 0.999)
        1 year
    0.998 (0.994 to 0.999)
    0.994 (0.985 to 0.998)
        1.5 year
    0.993 (0.988 to 0.996)
    0.990 (0.979 to 0.995)
        2 Years
    0.985 (0.979 to 0.990)
    0.985 (0.973 to 0.992)
        3 Years
    0.968 (0.958 to 0.975)
    0.960 (0.942 to 0.972)
        4 Years
    0.947 (0.935 to 0.956)
    0.950 (0.931 to 0.965)
        5 Years
    0.937 (0.925 to 0.948)
    0.929 (0.907 to 0.947)
        6 Years
    0.927 (0.913 to 0.938)
    0.921 (0.897 to 0.939)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From Day 1 up to 19 cycles (approximately 1 year) for the Treatment Period. From Data Cutoff up to approximately 6 years for the Safety Follow-up Period (SFU).
    Adverse event reporting additional description
    3 AEs during treatment resulted in eventual death, under the respective AE terms in Cohort A. 1 death during treatment, captured in "Number of deaths (all causes)" in Cohort A. Remaining 2 deaths included in SFU. SFU Period: no non-SAEs occurred at 5% threshold, 4 subjects excluded due to missing Principal Investigator signature in casebooks.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Cohort A: SC Herceptin by Needle/Syringe
    Reporting group description
    		 Subjects received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe.

    Reporting group title
    Cohort A: SC Herceptin by Needle/Syringe Safety Follow-up
    Reporting group description
    		 Subjects received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe.

    Reporting group title
    Cohort B: SC Herceptin by SID Safety Follow-up
    Reporting group description
    		 Subjects received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by subjects who were willing and judged competent by the HCP.

    Reporting group title
    Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Reporting group description
    		 Subjects received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by subjects who were willing and judged competent by the HCP.

    Serious adverse events
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort A: SC Herceptin by Needle/Syringe Safety Follow-up Cohort B: SC Herceptin by SID Safety Follow-up Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    242 / 1864 (12.98%)
    202 / 1862 (10.85%)
    53 / 707 (7.50%)
    84 / 709 (11.85%)
         number of deaths (all causes)
    28
    98
    45
    6
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    2 / 709 (0.28%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign pancreatic neoplasm
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Borderline serous tumour of ovary
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 1864 (0.05%)
    15 / 1862 (0.81%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 15
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial cancer
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian fibroma
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Schwannoma
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid adenoma
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine Cancer
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary Thyroid Cancer
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian Cancer Recurrent
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian Cancer
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastatic Gastric Cancer
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung Neoplasm Malignant
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Lung Cancer Metastatic
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Carcinoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric Cancer
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of Colon
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Vulval Cancer
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid Cancer
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal Cell Carcinoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic Carcinoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Ovarian Epithelial Cancer Metastatic
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Non-Hodgkin's Lymphoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphocytic Lymphoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive Lobular Breast Carcinoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive Ductal Breast Carcinoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular Carcinoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glioma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glioblastoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial Adenocarcinoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon Cancer Metastatic
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Chondroma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast Sarcoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast Neoplasm
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder Cancer
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal Cell Carcinoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovial Sarcoma Metastatic
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Malignant Melanoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    3 / 1862 (0.16%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 1864 (0.05%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arterial stenosis
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thromboangiitis Obliterans
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicose Vein
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive Urgency
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Anembryonic Gestation
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    11 / 1864 (0.59%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    7 / 709 (0.99%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 1
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device breakage
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 1864 (0.05%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 1864 (0.00%)
    6 / 1862 (0.32%)
    1 / 707 (0.14%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 6
    0 / 1
    0 / 1
    Device defective
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden Death
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    2 / 709 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaphylactic Shock
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Uterine polyp
         subjects affected / exposed
    2 / 1864 (0.11%)
    3 / 1862 (0.16%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast fibrosis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial hypertrophy
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    1 / 1864 (0.05%)
    2 / 1862 (0.11%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postmenopausal haemorrhage
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine haemorrhage
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast Necrosis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast Calcifications
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial Hyperplasia
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical Dysplasia
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibrocystic Breast Disease
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal Haemorrhage
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    2 / 1864 (0.11%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 1864 (0.11%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 1864 (0.00%)
    4 / 1862 (0.21%)
    1 / 707 (0.14%)
    2 / 709 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Organising pneumonia
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Painful respiration
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstructive Airways Disorder
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural Effusion
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Sarcoidosis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 1864 (0.05%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Panic attack
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Ejection fraction decreased
         subjects affected / exposed
    3 / 1864 (0.16%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood urea increased
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Radiation pneumonitis
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture displacement
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 1864 (0.05%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic arthropathy
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pubis Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower Limb Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foreign Body Aspiration
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    2 / 707 (0.28%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic Vertebral Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post Procedural Haematoma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint Dislocation
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incisional Hernia
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head Injury
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral Injury
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intentional Overdose
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal Compression Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral Neck Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    3 / 1862 (0.16%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle Fracture
         subjects affected / exposed
    0 / 1864 (0.00%)
    3 / 1862 (0.16%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure congestive
         subjects affected / exposed
    10 / 1864 (0.54%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    9 / 10
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 1864 (0.11%)
    6 / 1862 (0.32%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 1864 (0.05%)
    3 / 1862 (0.16%)
    3 / 707 (0.42%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracardiac Thrombus
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial Infarction
         subjects affected / exposed
    0 / 1864 (0.00%)
    6 / 1862 (0.32%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute Coronary Syndrome
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina Pectoris
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis Coronary Artery
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Atrial Flutter
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial Tachycardia
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac Hypertrophy
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardio-Respiratory Arrest
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 1864 (0.11%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 1864 (0.05%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carotid sinus syndrome
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 1864 (0.05%)
    2 / 1862 (0.11%)
    2 / 707 (0.28%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral sensorimotor neuropathy
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tension headache
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Relapsing-Remitting Multiple Sclerosis
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia Alzheimer's Type
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral Infarction
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amyotrophic Lateral Sclerosis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cerebral Haemorrhage
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cerebrovascular Disorder
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic Stroke
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    39 / 1864 (2.09%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    14 / 709 (1.97%)
         occurrences causally related to treatment / all
    5 / 39
    0 / 1
    0 / 0
    1 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    9 / 1864 (0.48%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    6 / 709 (0.85%)
         occurrences causally related to treatment / all
    0 / 11
    0 / 0
    0 / 0
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    2 / 709 (0.28%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    3 / 1864 (0.16%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thymus enlargement
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    2 / 1864 (0.11%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniere's disease
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Keratitis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    8 / 1864 (0.43%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    4 / 709 (0.56%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 0
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    5 / 1864 (0.27%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    3 / 1864 (0.16%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal discomfort
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal pain
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic colitis
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal Hernia
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal Fissure
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small Intestinal Obstruction
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum Intestinal
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Food Poisoning
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus Hernia
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal Obstruction
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper Gastrointestinal Haemorrhage
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    2 / 1864 (0.11%)
    3 / 1862 (0.16%)
    2 / 707 (0.28%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic Failure
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic Steatosis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bile Duct Obstruction
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bile Duct Stenosis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cholangitis Acute
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis bullous
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema nodosum
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic skin eruption
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient acantholytic dermatosis
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lichen Sclerosus
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary Bladder Polyp
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrotic Syndrome
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal Colic
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute Kidney Injury
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroiditis Subacute
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    2 / 1864 (0.11%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal Stenosis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scleroderma
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal Disorder
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mobility Decreased
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Exostosis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Neutropenic sepsis
         subjects affected / exposed
    9 / 1864 (0.48%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    6 / 1864 (0.32%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    5 / 1864 (0.27%)
    8 / 1862 (0.43%)
    2 / 707 (0.28%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 8
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 1864 (0.16%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    2 / 709 (0.28%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mastitis
         subjects affected / exposed
    3 / 1864 (0.16%)
    4 / 1862 (0.21%)
    0 / 707 (0.00%)
    2 / 709 (0.28%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    4 / 1864 (0.21%)
    4 / 1862 (0.21%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 1864 (0.16%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    4 / 1864 (0.21%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    2 / 1864 (0.11%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast abscess
         subjects affected / exposed
    2 / 1864 (0.11%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infectious colitis
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    2 / 1864 (0.11%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess of external auditory meatus
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendiceal abscess
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bartholin's abscess
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cellulitis
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 1864 (0.05%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal sepsis
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Lobar pneumonia
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymph node tuberculosis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningoencephalitis bacterial
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 1864 (0.05%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tracheobronchitis
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal infection
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    1 / 709 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Influenzal
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Streptococcal
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Sepsis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Post Procedural Cellulitis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Kidney Infection
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis Viral
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterobacter Sepsis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic Gangrene
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dengue Haemorrhagic Fever
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic Sinusitis
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary Tract Infection
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia Sepsis
         subjects affected / exposed
    0 / 1864 (0.00%)
    2 / 1862 (0.11%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    2 / 1864 (0.11%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 1864 (0.05%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decreased Appetite
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes Mellitus
         subjects affected / exposed
    0 / 1864 (0.00%)
    1 / 1862 (0.05%)
    0 / 707 (0.00%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 1864 (0.00%)
    0 / 1862 (0.00%)
    1 / 707 (0.14%)
    0 / 709 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort A: SC Herceptin by Needle/Syringe Cohort A: SC Herceptin by Needle/Syringe Safety Follow-up Cohort B: SC Herceptin by SID Safety Follow-up Cohort B: SC Herceptin by Single-Use Injection Device (SID)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1499 / 1864 (80.42%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    576 / 709 (81.24%)
    Investigations
    Ejection fraction decreased
         subjects affected / exposed
    80 / 1864 (4.29%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    36 / 709 (5.08%)
         occurrences all number
    85
    0
    0
    43
    Injury, poisoning and procedural complications
    Radiation skin injury
         subjects affected / exposed
    161 / 1864 (8.64%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    68 / 709 (9.59%)
         occurrences all number
    172
    0
    0
    78
    Vascular disorders
    Hot flush
         subjects affected / exposed
    164 / 1864 (8.80%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    72 / 709 (10.16%)
         occurrences all number
    179
    0
    0
    77
    Hypertension
         subjects affected / exposed
    142 / 1864 (7.62%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    35 / 709 (4.94%)
         occurrences all number
    183
    0
    0
    50
    Nervous system disorders
    Headache
         subjects affected / exposed
    228 / 1864 (12.23%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    73 / 709 (10.30%)
         occurrences all number
    344
    0
    0
    89
    Neuropathy peripheral
         subjects affected / exposed
    140 / 1864 (7.51%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    56 / 709 (7.90%)
         occurrences all number
    164
    0
    0
    65
    Paraesthesia
         subjects affected / exposed
    112 / 1864 (6.01%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    70 / 709 (9.87%)
         occurrences all number
    130
    0
    0
    87
    Dizziness
         subjects affected / exposed
    111 / 1864 (5.95%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    32 / 709 (4.51%)
         occurrences all number
    143
    0
    0
    35
    Peripheral sensory neuropathy
         subjects affected / exposed
    94 / 1864 (5.04%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    21 / 709 (2.96%)
         occurrences all number
    102
    0
    0
    25
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    381 / 1864 (20.44%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    132 / 709 (18.62%)
         occurrences all number
    496
    0
    0
    168
    Asthenia
         subjects affected / exposed
    221 / 1864 (11.86%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    85 / 709 (11.99%)
         occurrences all number
    327
    0
    0
    107
    Pyrexia
         subjects affected / exposed
    185 / 1864 (9.92%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    55 / 709 (7.76%)
         occurrences all number
    231
    0
    0
    67
    Oedema peripheral
         subjects affected / exposed
    160 / 1864 (8.58%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    45 / 709 (6.35%)
         occurrences all number
    185
    0
    0
    49
    Injection site erythema
         subjects affected / exposed
    128 / 1864 (6.87%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    52 / 709 (7.33%)
         occurrences all number
    326
    0
    0
    124
    Mucosal inflammation
         subjects affected / exposed
    105 / 1864 (5.63%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    53 / 709 (7.48%)
         occurrences all number
    126
    0
    0
    64
    Injection site pain
         subjects affected / exposed
    117 / 1864 (6.28%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    37 / 709 (5.22%)
         occurrences all number
    190
    0
    0
    107
    Injection site reaction
         subjects affected / exposed
    101 / 1864 (5.42%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    36 / 709 (5.08%)
         occurrences all number
    279
    0
    0
    58
    Pain
         subjects affected / exposed
    63 / 1864 (3.38%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    36 / 709 (5.08%)
         occurrences all number
    70
    0
    0
    41
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    130 / 1864 (6.97%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    43 / 709 (6.06%)
         occurrences all number
    159
    0
    0
    53
    Neutropenia
         subjects affected / exposed
    101 / 1864 (5.42%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    36 / 709 (5.08%)
         occurrences all number
    156
    0
    0
    45
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    380 / 1864 (20.39%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    130 / 709 (18.34%)
         occurrences all number
    540
    0
    0
    184
    Nausea
         subjects affected / exposed
    274 / 1864 (14.70%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    102 / 709 (14.39%)
         occurrences all number
    362
    0
    0
    133
    Constipation
         subjects affected / exposed
    153 / 1864 (8.21%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    62 / 709 (8.74%)
         occurrences all number
    200
    0
    0
    73
    Vomiting
         subjects affected / exposed
    129 / 1864 (6.92%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    38 / 709 (5.36%)
         occurrences all number
    160
    0
    0
    45
    Stomatitis
         subjects affected / exposed
    116 / 1864 (6.22%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    42 / 709 (5.92%)
         occurrences all number
    140
    0
    0
    47
    Abdominal pain
         subjects affected / exposed
    87 / 1864 (4.67%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    36 / 709 (5.08%)
         occurrences all number
    104
    0
    0
    45
    Dyspepsia
         subjects affected / exposed
    69 / 1864 (3.70%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    44 / 709 (6.21%)
         occurrences all number
    80
    0
    0
    50
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    190 / 1864 (10.19%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    56 / 709 (7.90%)
         occurrences all number
    223
    0
    0
    59
    Dyspnoea
         subjects affected / exposed
    115 / 1864 (6.17%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    47 / 709 (6.63%)
         occurrences all number
    126
    0
    0
    49
    Epistaxis
         subjects affected / exposed
    109 / 1864 (5.85%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    30 / 709 (4.23%)
         occurrences all number
    135
    0
    0
    35
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    177 / 1864 (9.50%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    74 / 709 (10.44%)
         occurrences all number
    251
    0
    0
    113
    Erythema
         subjects affected / exposed
    156 / 1864 (8.37%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    74 / 709 (10.44%)
         occurrences all number
    223
    0
    0
    86
    Alopecia
         subjects affected / exposed
    163 / 1864 (8.74%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    49 / 709 (6.91%)
         occurrences all number
    170
    0
    0
    50
    Pruritus
         subjects affected / exposed
    115 / 1864 (6.17%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    35 / 709 (4.94%)
         occurrences all number
    136
    0
    0
    40
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    108 / 1864 (5.79%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    50 / 709 (7.05%)
         occurrences all number
    125
    0
    0
    52
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    362 / 1864 (19.42%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    133 / 709 (18.76%)
         occurrences all number
    471
    0
    0
    160
    Myalgia
         subjects affected / exposed
    260 / 1864 (13.95%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    84 / 709 (11.85%)
         occurrences all number
    349
    0
    0
    107
    Pain in extremity
         subjects affected / exposed
    194 / 1864 (10.41%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    49 / 709 (6.91%)
         occurrences all number
    248
    0
    0
    63
    Back pain
         subjects affected / exposed
    114 / 1864 (6.12%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    42 / 709 (5.92%)
         occurrences all number
    136
    0
    0
    44
    Musculoskeletal pain
         subjects affected / exposed
    89 / 1864 (4.77%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    36 / 709 (5.08%)
         occurrences all number
    107
    0
    0
    40
    Bone pain
         subjects affected / exposed
    70 / 1864 (3.76%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    40 / 709 (5.64%)
         occurrences all number
    80
    0
    0
    53
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    146 / 1864 (7.83%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    58 / 709 (8.18%)
         occurrences all number
    190
    0
    0
    79
    Upper respiratory tract infection
         subjects affected / exposed
    113 / 1864 (6.06%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    21 / 709 (2.96%)
         occurrences all number
    132
    0
    0
    25
    Urinary tract infection
         subjects affected / exposed
    94 / 1864 (5.04%)
    0 / 1862 (0.00%)
    0 / 707 (0.00%)
    32 / 709 (4.51%)
         occurrences all number
    114
    0
    0
    43

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Nov 2012
    The amendment allowed subjects to be treated with SC Herceptin according to indication and to allow a sub-population of subjects to be enrolled to provide complementary safety data for regulatory purposes. The duration of treatment-free follow-up was extended from a minimum of 2 years to a minimum of 5 years, and the AE reporting timeframe was revised.
    18 Mar 2013
    The protocol was amended to clarify the timeframe for AE reporting as well as the definition of "treatment period". Subjects were also allowed the opportunity to self-administer SC Herceptin via SID at the discretion and supervision of the HCP.

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

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

    European Medicines Agency © 1995-Mon Oct 27 05:47:24 CET 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA