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    Clinical Trial Results:
    A Multicenter Phase III Randomized Trial of Adjuvant Therapy for Patients With HER2-Positive Node-Positive or High Risk Node-Negative Breast Cancer Comparing Chemotherapy Plus Trastuzumab With Chemotherapy Plus Trastuzumab Plus Bevacizumab

    Summary
    EudraCT number
    		 2007-005182-35
    Trial protocol
    		 DE   FR   GB   IE   LV   ES   BE   AT   SK   CZ   HU   PT   EE   SE   SI   IT   BG   GR  
    Global end of trial date
    17 Apr 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    05 Feb 2016
    First version publication date
    05 Feb 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    BO20906
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00625898
    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
    10 Jul 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Apr 2014
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    This is an international, multi-center, open-label, randomized Phase III trial of adjuvant therapy for participants with HER2-positive node-positive or high risk node-negative breast cancer to determine whether the addition of bevacizumab of two designated regimens of chemotherapy plus trastuzumab (TCHB→HB; THB→FEC→HB) improves efficacy and safety of two designated regimen of chemotherapy plus trastuzumab (TCH→H; TH→FEC→H). TCHB→HB = docetaxel (T), carboplatin (C), trastuzumab (H), bevacizumab (B) followed by trastuzumab (T) and bevacizumab (B). THB→FEC→HB = THB followed by 5-fluorouracil (F), epirubicin (E), and cyclophosphamide (C) followed by HB. TCH→H = TCH followed by H. TH→FEC→H = TH followed by FEC followed by H.
    Protection of trial subjects
    Study BO20906 was conducted in accordance with the principles of the Declaration of Helsinki, and in accordance with the protocol, Good Clinical Practice Guidelines, and applicable regulatory requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 May 2008
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 10
    Country: Number of subjects enrolled
    Australia: 76
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 25
    Country: Number of subjects enrolled
    Brazil: 79
    Country: Number of subjects enrolled
    Canada: 268
    Country: Number of subjects enrolled
    China: 147
    Country: Number of subjects enrolled
    Croatia: 19
    Country: Number of subjects enrolled
    Egypt: 12
    Country: Number of subjects enrolled
    Hong Kong: 15
    Country: Number of subjects enrolled
    Israel: 44
    Country: Number of subjects enrolled
    Korea, Republic of: 328
    Country: Number of subjects enrolled
    Mexico: 10
    Country: Number of subjects enrolled
    Peru: 34
    Country: Number of subjects enrolled
    Philippines: 39
    Country: Number of subjects enrolled
    Romania: 31
    Country: Number of subjects enrolled
    Russian Federation: 82
    Country: Number of subjects enrolled
    Serbia: 10
    Country: Number of subjects enrolled
    South Africa: 19
    Country: Number of subjects enrolled
    Taiwan: 48
    Country: Number of subjects enrolled
    Thailand: 28
    Country: Number of subjects enrolled
    United States: 984
    Country: Number of subjects enrolled
    Greece: 6
    Country: Number of subjects enrolled
    Hungary: 14
    Country: Number of subjects enrolled
    Ireland: 41
    Country: Number of subjects enrolled
    Italy: 117
    Country: Number of subjects enrolled
    Latvia: 6
    Country: Number of subjects enrolled
    Poland: 138
    Country: Number of subjects enrolled
    Portugal: 3
    Country: Number of subjects enrolled
    Slovenia: 3
    Country: Number of subjects enrolled
    Spain: 243
    Country: Number of subjects enrolled
    Sweden: 18
    Country: Number of subjects enrolled
    United Kingdom: 55
    Country: Number of subjects enrolled
    Austria: 62
    Country: Number of subjects enrolled
    Belgium: 59
    Country: Number of subjects enrolled
    Bulgaria: 30
    Country: Number of subjects enrolled
    Estonia: 5
    Country: Number of subjects enrolled
    France: 127
    Country: Number of subjects enrolled
    Germany: 274
    Worldwide total number of subjects
    3509
    EEA total number of subjects
    1251
    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)
    3199
    From 65 to 84 years
    310
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Prior to the screening evaluation, participants were informed of the nature of the study drug, intended purpose, possible benefits, and possible adverse experiences. Participants were screened by central testing for resected node-positive or high risk node-negative invasive breast cancer HER2-positive and randomized.

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Chemotherapy + Trastuzumab
    Arm description
    		 Non-anthracycline based regimen (Group 1A TCH→H): participants received 6 cycles of docetaxel 75 milligrams per square meter (mg/m^2) intravenously (IV) along with carboplatin 6 milligrams per milliliter per minute (mg/mL/min) area under the curve (AUC) IV, every three weeks (q3w) plus (+) trastuzumab (first dose: 8 milligrams per kilogram [mg/kg] IV and then 6 mg/kg IV) followed by trastuzumab alone (6 mg/kg) every 3 weeks to complete one year of therapy. Anthracycline based regimen (Group 2A: TH→FEC→H): participants received 3 cycles q3w of trastuzumab (first dose: 8 mg/kg Cycle 1 and 6 mg/kg Doses 2 and 3) and docetaxel 100 mg/m^2 IV followed by 3 cycles q3w of 5-Fluorouracil (5-FU) 600 mg/m^2 IV push; epirubicin 90 mg/m^2 IV; cyclophosphamide 600 mg/m^2 IV and then trastuzumab alone (Dose 4: 8 mg/kg Cycle 1 and then 6 mg/kg) q3w to complete one year of therapy.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants in non-Anthracycline based regimen (TCH→H) received 75 mg/m^2 docetaxel IV over 60 minutes, q3w for 6 cycles. Participants in anthracycline based regimen (TH→FEC→H) received 100 mg/m^2 docetaxelIV over 60 minutes, q3w for 3 cycles.

    Investigational medicinal product name
    5-Fluorouracil (5-FU)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants in Anthracycline based regimen(TH→FEC→H) received 600 mg/m^2 IV push 5-FU, q3w for 3 cycles.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants in non-anthracycline based regimen (TCH→H) received AUC 6 mg/mL/min IV carboplatin over 30 to 60 minutes, q3w for 6 cycles.

    Investigational medicinal product name
    Trastuzumab
    Investigational medicinal product code
    Other name
    Herceptin
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received trastuzumab (first dose: 8 mg/kg IV and then 6 mg/kg) IV q3w to complete one year of therapy in non-anthracycline based regimen (TCH→H). In anthracycline based regimen (TH→FEC→H), participants received 3 cycles of trastuzumab (first dose: 8 mg/kg Cycle 1 and 6 mg/kg Doses 2 and 3) and then after the completion of FEC regimen, participant received trastuzumab (Dose 4: 8 mg/kg Cycle 1 and then 6 mg/kg) q3w to complete one year on therapy.

    Investigational medicinal product name
    Epirubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants in anthracycline based regimen (TH→FEC→H) received 90 mg/m^2 IV epirubicin, q3w for 3 cycles.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants in anthracycline based regimen (TH→FEC→H) received 600 mg/m^2 IV cyclophosphamide, q3w for 3 cycles.

    Arm title
    		 Chemotherapy + Trastuzumab + Bevacizumab
    Arm description
    		 Non-anthracycline based regimen (Group 1B:TCHB→HB): Participants received 6 cycles of docetaxel 75 mg/m^2 IV along with carboplatin 6 mg/mL/min AUC IV, q3w + trastuzumab (8 mg/kg IV in Cycle 1 and then 6 mg/kg IV) and bevacizumab (15 mg/kg IV) followed by trastuzumab (6 mg/kg) +bevacizumab (15 mg/kg IV) every 3 weeks to complete one year of therapy. Anthracycline based regimen (Group 2B: THB→FEC→HB): Participants received 3 cycles of q3w of trastuzumab (first dose: 8 mg/kg Cycle 1 and 6 mg/kg Doses 2 and 3), bevacizumab 15 mg/kg IV, and docetaxel 100 mg/m^2 IV followed by 3 cycles q3w of 5-FU 600 mg/m^2 IV push; epirubicin 90 mg/m^2 IV; cyclophosphamide 600 mg/m^2 IV and then trastuzumab (Dose 4: 8 mg/kg Cycle 1 and 6 mg/kg) and bevacizumab (15 mg/kg IV) every 3 weeks to complete one year of therapy.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants in non-Anthracycline based regimen (TCH→H) received 75 mg/m^2 docetaxel IV over 60 minutes, q3w for 6 cycles. Participants in anthracycline based regimen (TH→FEC→H) received 100 mg/m^2 docetaxelIV over 60 minutes, q3w for 3 cycles.

    Investigational medicinal product name
    5-Fluorouracil (5-FU)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants in Anthracycline based regimen(TH→FEC→H) received 600 mg/m^2 IV push 5-FU, q3w for 3 cycles.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants in non-anthracycline based regimen (TCH→H) received AUC 6 mg/mL/min IV carboplatin over 30 to 60 minutes, q3w for 6 cycles.

    Investigational medicinal product name
    Trastuzumab
    Investigational medicinal product code
    Other name
    Herceptin
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received trastuzumab (first dose: 8 mg/kg IV and then 6 mg/kg) IV q3w to complete one year of therapy in non-anthracycline based regimen (TCH→H). In anthracycline based regimen (TH→FEC→H), participants received 3 cycles of trastuzumab (first dose: 8 mg/kg Cycle 1 and 6 mg/kg Doses 2 and 3) and then after the completion of FEC regimen, participant received trastuzumab (Dose 4: 8 mg/kg Cycle 1 and then 6 mg/kg) q3w to complete one year on therapy.

    Investigational medicinal product name
    Epirubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants in anthracycline based regimen (TH→FEC→H) received 90 mg/m^2 IV epirubicin, q3w for 3 cycles.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants in anthracycline based regimen (TH→FEC→H) received 600 mg/m^2 IV cyclophosphamide, q3w for 3 cycles.

    Investigational medicinal product name
    Bevacizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received 15 mg/kg of bevacizumab IV q3w every 3 weeks to complete one year of therapy q3w for 17 cycles in non-anthracycline based regimen(TCHB→HB). In anthracycline based regimen (THB→FEC→HB), participants received 3 cycles of bevacizumab IV 15 mg/kg and then after the completion of FEC regimen, participants received bevacizumab IV 15 mg/kg every 3 weeks to complete one year on therapy.

    Number of subjects in period 1
    		Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Started
    1757
    1752
    Treated
    1740
    1732
    Assigned treatment received
    1739
    1721
    Incorrect treatment received
    1
    11
    Completed
    0
    0
    Not completed
    1757
    1752
         Participants died
    78
    70
         Lost to follow-up
    116
    154
         Alive in follow-up
    1563
    1528

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Chemotherapy + Trastuzumab
    Reporting group description
    		 Non-anthracycline based regimen (Group 1A TCH→H): participants received 6 cycles of docetaxel 75 milligrams per square meter (mg/m^2) intravenously (IV) along with carboplatin 6 milligrams per milliliter per minute (mg/mL/min) area under the curve (AUC) IV, every three weeks (q3w) plus (+) trastuzumab (first dose: 8 milligrams per kilogram [mg/kg] IV and then 6 mg/kg IV) followed by trastuzumab alone (6 mg/kg) every 3 weeks to complete one year of therapy. Anthracycline based regimen (Group 2A: TH→FEC→H): participants received 3 cycles q3w of trastuzumab (first dose: 8 mg/kg Cycle 1 and 6 mg/kg Doses 2 and 3) and docetaxel 100 mg/m^2 IV followed by 3 cycles q3w of 5-Fluorouracil (5-FU) 600 mg/m^2 IV push; epirubicin 90 mg/m^2 IV; cyclophosphamide 600 mg/m^2 IV and then trastuzumab alone (Dose 4: 8 mg/kg Cycle 1 and then 6 mg/kg) q3w to complete one year of therapy.

    Reporting group title
    Chemotherapy + Trastuzumab + Bevacizumab
    Reporting group description
    		 Non-anthracycline based regimen (Group 1B:TCHB→HB): Participants received 6 cycles of docetaxel 75 mg/m^2 IV along with carboplatin 6 mg/mL/min AUC IV, q3w + trastuzumab (8 mg/kg IV in Cycle 1 and then 6 mg/kg IV) and bevacizumab (15 mg/kg IV) followed by trastuzumab (6 mg/kg) +bevacizumab (15 mg/kg IV) every 3 weeks to complete one year of therapy. Anthracycline based regimen (Group 2B: THB→FEC→HB): Participants received 3 cycles of q3w of trastuzumab (first dose: 8 mg/kg Cycle 1 and 6 mg/kg Doses 2 and 3), bevacizumab 15 mg/kg IV, and docetaxel 100 mg/m^2 IV followed by 3 cycles q3w of 5-FU 600 mg/m^2 IV push; epirubicin 90 mg/m^2 IV; cyclophosphamide 600 mg/m^2 IV and then trastuzumab (Dose 4: 8 mg/kg Cycle 1 and 6 mg/kg) and bevacizumab (15 mg/kg IV) every 3 weeks to complete one year of therapy.

    Reporting group values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab Total
    Number of subjects
    		 1757 1752 3509
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 50.7 ± 10 50.8 ± 10.25 -
    Gender categorical
    Units: Subjects
        Female
    		 1757 1752 3509
        Male
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Chemotherapy + Trastuzumab
    Reporting group description
    		 Non-anthracycline based regimen (Group 1A TCH→H): participants received 6 cycles of docetaxel 75 milligrams per square meter (mg/m^2) intravenously (IV) along with carboplatin 6 milligrams per milliliter per minute (mg/mL/min) area under the curve (AUC) IV, every three weeks (q3w) plus (+) trastuzumab (first dose: 8 milligrams per kilogram [mg/kg] IV and then 6 mg/kg IV) followed by trastuzumab alone (6 mg/kg) every 3 weeks to complete one year of therapy. Anthracycline based regimen (Group 2A: TH→FEC→H): participants received 3 cycles q3w of trastuzumab (first dose: 8 mg/kg Cycle 1 and 6 mg/kg Doses 2 and 3) and docetaxel 100 mg/m^2 IV followed by 3 cycles q3w of 5-Fluorouracil (5-FU) 600 mg/m^2 IV push; epirubicin 90 mg/m^2 IV; cyclophosphamide 600 mg/m^2 IV and then trastuzumab alone (Dose 4: 8 mg/kg Cycle 1 and then 6 mg/kg) q3w to complete one year of therapy.

    Reporting group title
    Chemotherapy + Trastuzumab + Bevacizumab
    Reporting group description
    		 Non-anthracycline based regimen (Group 1B:TCHB→HB): Participants received 6 cycles of docetaxel 75 mg/m^2 IV along with carboplatin 6 mg/mL/min AUC IV, q3w + trastuzumab (8 mg/kg IV in Cycle 1 and then 6 mg/kg IV) and bevacizumab (15 mg/kg IV) followed by trastuzumab (6 mg/kg) +bevacizumab (15 mg/kg IV) every 3 weeks to complete one year of therapy. Anthracycline based regimen (Group 2B: THB→FEC→HB): Participants received 3 cycles of q3w of trastuzumab (first dose: 8 mg/kg Cycle 1 and 6 mg/kg Doses 2 and 3), bevacizumab 15 mg/kg IV, and docetaxel 100 mg/m^2 IV followed by 3 cycles q3w of 5-FU 600 mg/m^2 IV push; epirubicin 90 mg/m^2 IV; cyclophosphamide 600 mg/m^2 IV and then trastuzumab (Dose 4: 8 mg/kg Cycle 1 and 6 mg/kg) and bevacizumab (15 mg/kg IV) every 3 weeks to complete one year of therapy.

    Primary: Invasive Disease-Free Survival (IDFS) Time

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    End point title
    		 Invasive Disease-Free Survival (IDFS) Time
    End point description
    IDFS was defined as the time from randomization to local recurrence following mastectomy, invasive local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, invasive contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix, colon carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. '9999' for median, '999' and '99999' for lower and upper range of 95% confidence interval (CI), respectively in results field signifies 'Not Available'; the median and 95% CI were not reached as majority of participants were censored. Intent-to-treat population (ITT) was defined as all participants who were randomized to study treatment irrespective of exposure to the assigned study treatment.
    End point type
    Primary
    End point timeframe
    Every 12 months during targeted therapy and from completion of targeted therapy through Year 10 (until data cutoff: 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1757
    1752
    Units: Months
        median (confidence interval 95%)
    9999 (999 to 99999)
    9999 (999 to 99999)
    Statistical analysis title
    		 IDFS Time
    Comparison groups
    Chemotherapy + Trastuzumab + Bevacizumab v Chemotherapy + Trastuzumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.961
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.25

    Primary: Percentage of Participants With IDFS Events

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    End point title
    		 Percentage of Participants With IDFS Events [1]
    End point description
    IDFS was defined as the time from randomization to local recurrence following mastectomy, invasive local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, invasive contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix, colon carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. ITT population was defined as all participants who were randomized to study treatment irrespective of exposure to the assigned study treatment.
    End point type
    Primary
    End point timeframe
    Every 12 months during targeted therapy and from completion of targeted therapy through Year 10 (until data cutoff: 17 April 2014)
    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: No statistical analysis was performed for the percentage of participants with an event.
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1757
    1752
    Units: Percentage of participants
    number (not applicable)
        Percentage of Participants with Events
    8.3
    8.4
    No statistical analyses for this end point

    Secondary: Disease-Free Survival (DFS) Time

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    End point title
    		 Disease-Free Survival (DFS) Time
    End point description
    DFS was defined as the time from randomization to local recurrence following mastectomy, local recurrence in the ipsilateral breast following lumpectomy (invasive or non-invasive), regional recurrence, distant recurrence, contralateral breast cancer (invasive or non-invasive), second primary cancer (other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix, colon carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. ITT population was defined as all participants who were randomized to study treatment irrespective of exposure to the assigned study treatment. '9999' for median, '999' and '99999' for lower and upper range of 95% CI, respectively in results field signifies 'Not Available'; the median and 95% CI were not reached as majority of participants were censored.
    End point type
    Secondary
    End point timeframe
    Every 12 months during targeted therapy and from completion of targeted therapy through Year 10 (until data cutoff: 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1757
    1752
    Units: Months
        median (confidence interval 95%)
    9999 (999 to 99999)
    9999 (999 to 99999)
    Statistical analysis title
    		 DFS Time
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8402
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.29

    Secondary: Percentage of Participants With DFS Event

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    End point title
    		 Percentage of Participants With DFS Event
    End point description
    DFS was defined as the time from randomization to local recurrence following mastectomy, local recurrence in the ipsilateral breast following lumpectomy (invasive or non-invasive), regional recurrence, distant recurrence, contralateral breast cancer (invasive or non-invasive), second primary cancer (other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix, colon carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. ITT population was defined as all participants who were randomized to study treatment irrespective of exposure to the assigned study treatment.
    End point type
    Secondary
    End point timeframe
    Every 12 months during targeted therapy and from completion of targeted therapy through Year 10 (until data cutoff: 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1757
    1752
    Units: Percentage of participants
        number (not applicable)
    8.3
    8.6
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) Time

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    End point title
    		 Overall Survival (OS) Time
    End point description
    OS was defined as the time from randomization to death from any cause. Participants without an event at the time of the clinical cutoff were censored at the last date the participant was known to be alive. ITT population was defined as all participants who were randomized to study treatment irrespective of exposure to the assigned study treatment. '9999' for median, '999' and '99999' for lower and upper range of 95% CI, respectively in results field signifies 'Not Available'; because the median and 95% CI was not reached as majority of participants were censored.
    End point type
    Secondary
    End point timeframe
    Cycles 1-17, then every 6 months until Year 6 and every 12 months through year 10 (until cutoff: 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1757
    1752
    Units: Months
        median (confidence interval 95%)
    9999 (999 to 99999)
    9999 (999 to 99999)
    Statistical analysis title
    		 OS Time
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5147
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 1.28

    Secondary: Percentage of Participants Who Died

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    End point title
    		 Percentage of Participants Who Died
    End point description
    OS was defined as the time from randomization to death from any cause. Participants without an event at the time of the clinical cutoff were censored at the last date the participant was known to be alive. ITT population was defined as all participants who were randomized to study treatment irrespective of exposure to the assigned study treatment.
    End point type
    Secondary
    End point timeframe
    Cycles 1-17, then every 6 months until Year 6 and every 12 months through year 10 (until cutoff: 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1757
    1752
    Units: Percentage of participants
        number (not applicable)
    3.5
    3.1
    No statistical analyses for this end point

    Secondary: Recurrence-Free Interval (RFI) Time

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    End point title
    		 Recurrence-Free Interval (RFI) Time
    End point description
    RFI was defined as the time from randomization until local, regional, or distant recurrence. Participants without an event at the time of the clinical cutoff were censored at the last date the participant was known to be event free. ITT population was defined as all participants who were randomized to study treatment irrespective of exposure to the assigned study treatment. '99999' for median, '999' and '99999' for lower and upper range of 95% CI, respectively in results field signifies 'Not Available'; because the median and 95% CI was not reached as majority of participants were censored.
    End point type
    Secondary
    End point timeframe
    Every 12 months during targeted therapy and from completion of targeted therapy through Year 10 (until data cutoff: 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1757
    1752
    Units: Months
        median (confidence interval 95%)
    9999 (999 to 99999)
    9999 (999 to 99999)
    Statistical analysis title
    		 RFI Time
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4331
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.43

    Secondary: Percentage of Participants With Local, Regional, or Distant Recurrence

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    End point title
    		 Percentage of Participants With Local, Regional, or Distant Recurrence
    End point description
    RFI was defined as the time from randomization until local, regional, or distant recurrence. Participants without an event at the time of the clinical cutoff were censored at the last date the participant was known to be event free. ITT population was defined as all participants who were randomized to study treatment irrespective of exposure to the assigned study treatment.
    End point type
    Secondary
    End point timeframe
    Every 12 months during targeted therapy and from completion of targeted therapy through Year 10 (until data cutoff: 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1757
    1752
    Units: Percentage of participants
        number (not applicable)
    6.3
    7.1
    No statistical analyses for this end point

    Secondary: Distant Recurrence-Free Interval (DRFI) Time

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    End point title
    		 Distant Recurrence-Free Interval (DRFI) Time
    End point description
    DRFI was defined as the time from randomization until distant disease recurrence only. Participants without an event at the time of the clinical cutoff were censored at the last date the participant was known to be event free. ITT population was defined as all participants who were randomized to study treatment irrespective of exposure to the assigned study treatment. '9999' for median, '999' and '99999' for lower and upper range of 95% CI, respectively in results field signifies 'Not Available'; because the median and 95% CI was not reached as majority of participants were censored.
    End point type
    Secondary
    End point timeframe
    Every 12 months during targeted therapy and from completion of targeted therapy through Year 10 (until data cutoff: 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1757
    1752
    Units: Months
        median (confidence interval 95%)
    9999 (999 to 99999)
    9999 (999 to 99999)
    Statistical analysis title
    		 DRFI Time
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5829
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 1.43

    Secondary: Percentage of Participants With Distant Recurrence

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    End point title
    		 Percentage of Participants With Distant Recurrence
    End point description
    DRFI was defined as the time from randomization until distant disease recurrence only. Participants without an event at the time of the clinical cutoff were censored at the last date the participant was known to be event free. ITT population was defined as all participants who were randomized to study treatment irrespective of exposure to the assigned study treatment.
    End point type
    Secondary
    End point timeframe
    Every 12 months during targeted therapy and from completion of targeted therapy through Year 10 (until data cutoff: 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1757
    1752
    Units: Percentage of participants
    number (not applicable)
        Percentage of Participants with Events
    5.4
    5.9
        Percentage of Participants without Events
    94.6
    94.1
    No statistical analyses for this end point

    Secondary: IDFS by Treatment and Biomarker Levels

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    End point title
    		 IDFS by Treatment and Biomarker Levels
    End point description
    IDFS was defined as the time from randomization to local recurrence following mastectomy, invasive local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, invasive contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix, colon carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. The baseline sample median biomarker concentration was used as the cut point to group participants as high (greater than median) versus low (less than or equal to median) levels of concentration. The Biomarker Evaluable Protein Plasma Population (BEP) was defined as all participants in the ITT population who received any component of study medication and had a baseline biomarker sample available for analysis. '9999' for median, '999' and '99999' for lower and upper range of
    End point type
    Secondary
    End point timeframe
    Every 12 months during targeted therapy and from completion of targeted therapy through Year 10 (until data cutoff: 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1757
    1752
    Units: Months
    median (confidence interval 95%)
        E-selectin (High level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        E-selectin (Low level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Intercellular cell adhesion molecule 1(High level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Intercellular cell adhesion molecule 1 (Low level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Interleukin-8 (High level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Interleukin-8 (Low level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Platelet-derived growth factor-C (High level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Platelet-derived growth factor-C (Low level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Placental growth factor (High level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Placental growth factor (Low level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Vascular endothelial growth factor-A (High level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Vascular endothelial growth factor-A (Low level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Vascular endothelial growth factor-C (High level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Vascular endothelial growth factor-C (Low level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        VEFGR-1 (High level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        VEFGR-1 (Low level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        VEFGR-2 (High level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        VEFGR-2 (Low level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        VEFGR-3 (High level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        VEFGR-3 (Low level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Basic fibroblast growth factor (High level)
    9999 (999 to 99999)
    9999 (999 to 99999)
        Basic fibroblast growth factor (Low level)
    9999 (999 to 99999)
    9999 (999 to 99999)
    Statistical analysis title
    		 E-selectin (High level)
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0328
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.05
         upper limit
    		 6.22
    Statistical analysis title
    		 E-selectin (Low level)
    Statistical analysis description
    Number of participants for this analysis were 149 and 155 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9234
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 2.61
    Statistical analysis title
    		 Intercellular cell adhesion molecule 1(High level)
    Statistical analysis description
    Number of participants for this analysis were 156 and 147 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2161
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 3.74
    Statistical analysis title
    		 Intercellular cell adhesion molecule 1(Low level)
    Statistical analysis description
    Number of participants for this analysis were 149 and 155 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2397
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 4.95
    Statistical analysis title
    		 Interleukin-8 (High level)
    Statistical analysis description
    Number of participants for this analysis were 235 and 230 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7089
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 1.76
    Statistical analysis title
    		 Interleukin-8 (Low level)
    Statistical analysis description
    Number of participants for this analysis were 235 and 232 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3652
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 2.7
    Statistical analysis title
    		 Platelet-derived growth factor-C (High level)
    Statistical analysis description
    Number of participants for this analysis were 234 and 235 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8598
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 2.26
    Statistical analysis title
    		 Platelet-derived growth factor-C (Low level)
    Statistical analysis description
    Number of participants for this analysis were 239 and 230 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.593
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 2.23
    Statistical analysis title
    		 Placental growth factor (High level)
    Statistical analysis description
    Number of participants for this analysis were 126 and 119 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0994
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.82
         upper limit
    		 6.77
    Statistical analysis title
    		 Placental growth factor (Low level)
    Statistical analysis description
    Number of participants for this analysis were 179 and 183 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5226
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 2.82
    Statistical analysis title
    		 Vascular endothelial growth factor-A (High level)
    Statistical analysis description
    Number of participants for this analysis were 242 and 220 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8603
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 2.02
    Statistical analysis title
    		 Vascular endothelial growth factor-A (Low level)
    Statistical analysis description
    Number of participants for this analysis were 226 and 237 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.548
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 2.78
    Statistical analysis title
    		 Vascular endothelial growth factor-C (High level)
    Statistical analysis description
    Number of participants for this analysis were 229 and 240 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7868
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 2.16
    Statistical analysis title
    		 Vascular endothelial growth factor-C (Low level)
    Statistical analysis description
    Number of participants for this analysis were 244 and 225 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6216
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 2.43
    Statistical analysis title
    		 VEFGR-1 (High level)
    Statistical analysis description
    Number of participants for this analysis were 210 and 211 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.446
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 2.63
    Statistical analysis title
    		 VEFGR-1 (Low level)
    Statistical analysis description
    Number of participants for this analysis were 260 and 251 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7039
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.44
         upper limit
    		 1.75
    Statistical analysis title
    		 VEFGR-2 (High level)
    Statistical analysis description
    Number of participants for this analysis were 245 and 221 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1997
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 1.28
    Statistical analysis title
    		 VEFGR-2 (Low level)
    Statistical analysis description
    Number of participants for this analysis were 225 and 241 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0383
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 4.65
    Statistical analysis title
    		 VEFGR-3 (High level)
    Statistical analysis description
    Number of participants for this analysis were 238 and 228 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5419
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 2.5
    Statistical analysis title
    		 VEFGR-3 (Low level)
    Statistical analysis description
    Number of participants for this analysis were 232 and 234 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8534
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 2.11
    Statistical analysis title
    		 Basic fibroblast growth factor (High level)
    Statistical analysis description
    Number of participants for this analysis were 235 and 231 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2761
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 1.36
    Statistical analysis title
    		 Basic fibroblast growth factor (Low level)
    Statistical analysis description
    Number of participants for this analysis were 235 and 231 for Chemotherapy + Trastuzumab and Chemotherapy + Trastuzumab + Bevacizumab, respectively instead of 3509.
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.048
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.99
         upper limit
    		 4.46

    Secondary: Percentage of Participants with Cardiac Events

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    End point title
    		 Percentage of Participants with Cardiac Events
    End point description
    The number of participants with cardiac toxicity was defined as those who had cardiac events of North Hampton Youth Association (NHYA) III and IV of left ventricular dysfunction (LVD) and/or who had definite or probable cardiac death. Other cardiac events included Grade 3 or 4 cardiac ischemia/infarction and Grade 3 systolic or diastolic dysfunction with NYHA Class II symptoms. The safety population consisted of all participants who received any study treatment, which was defined as at least one full or partial dose of bevacizumab, trastuzumab, docetaxel, carboplatin, or FEC.
    End point type
    Secondary
    End point timeframe
    Within 3 days before each chemotherapy cycle from Cycle 2, 2-3 weeks after last chemotherapy dose during targeted therapy, every 6, 12 months from completion of targeted therapy through Year 5 and Years 6, respectively (until data cutoff 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1750
    1722
    Units: Percentage of participants
    number (confidence interval 95%)
        Percentage of Participants with Events
    25.5 (23 to 28)
    51.3 (49 to 54)
    Statistical analysis title
    		 Percentage of Participants With Cardiac Events
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3472
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 < 0.0001
    Method
    		 Fisher exact
    Confidence interval

    Secondary: IDFS Within Chemotherapy Cohorts

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    End point title
    		 IDFS Within Chemotherapy Cohorts
    End point description
    IDFS was defined as the time from randomization to local recurrence following mastectomy, invasive local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, invasive contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix, colon carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. IDFS was identified within chemotherapy cohort of docetaxel/carboplatin plus trastuzumab with or without bevacizumab and of docetaxel plus trastuzumab given with or without bevacizumab followed by 5-FU, epirubicin, cyclophosphamide (FEC). ITT population was defined as all participants who were randomized to study treatment irrespective of exposure to the assigned study treatment.
    End point type
    Secondary
    End point timeframe
    Every 12 months during targeted therapy and from completion of targeted therapy through Year 10 (until data cutoff: 17 April 2014)
    End point values
    		 Chemotherapy + Trastuzumab Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects analysed
    1606 [2]
    1605 [3]
    Units: Months
    median (confidence interval 95%)
        Docetaxel+Carboplatin+Trastuzumab; n=1606,1605
    9999 (999 to 99999)
    9999 (999 to 99999)
        Docetaxel+Trastuzumab+FEC; n=134,127
    9999 (999 to 99999)
    9999 (999 to 99999)
    Notes
    [2] - n (number) = participants analyzed at specified time for this endpoint.
    [3] - n (number) = participants analyzed at specified time for this endpoint.
    Statistical analysis title
    		 Non-Antracycline based regimen
    Comparison groups
    Chemotherapy + Trastuzumab v Chemotherapy + Trastuzumab + Bevacizumab
    Number of subjects included in analysis
    3211
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9354
    Method
    		 Logrank (stratified)
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 1.28
    Statistical analysis title
    		 Antracycline based regimen
    Comparison groups
    Chemotherapy + Trastuzumab + Bevacizumab v Chemotherapy + Trastuzumab
    Number of subjects included in analysis
    3211
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5164
    Method
    		 Logrank (stratified)
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 1.73

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline to the end of study (74 months)
    Adverse event reporting additional description
    The Safety Population consisted of all participants who received any study treatment, which was defined as at least one full or partial dose of bevacizumab, trastuzumab, docetaxel, carboplatin, or FEC.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Safety Cohort 1: Chemo + Trastuzumab (<18 month)
    Reporting group description
    		 Safety Cohort 1 was set up with first 300 enrolled from Group 1 (non anthracycline regimen) and the first 278 participants from Group 2 (anthracycline regimen). This reporting group included participants in Safety Cohort 1 who received chemo+trastuzumab (H) but no bevacizumab (B). Participants from Group 1 (TCH→H) received: 6 q3w cycles of docetaxel (T; 75 mg/m^2) IV+carboplatin (C;6 mg/mL/min) AUC IV, with q3w 1­year of H (8 mg/kg in Cycle 1 and then 6 mg/kg) IV. Participants from Group 2 (TH→FEC→H) received: 3 q3w cycles of H (8 mg/kg dose 1, 6 mg/kg doses 2 & 3) IV + T (100 mg/m^2 IV), then 3 q3w cycles of 5­FU (600 mg/m^2) IV + epirubicin (90 mg/m^2) IV + cyclophosphamide (600 mg/m^2) IV, and then H alone q3w (8 mg/kg dose 4, then 6 mg/kg) IV to complete 1 year of therapy. In this safety cohort, all grades of AEs until 18 months after randomization were collected and reported.

    Reporting group title
    Safety Cohort 1: Chemo + Trastuzumab + Bevacizumab (<18 month)
    Reporting group description
    		 Safety Cohort 1 was set up with the first 300 participants enrolled from Group 1 (non anthracycline regimen) and the first 278 participants from Group 2 (anthracycline regimen). This reporting group included participants in Safety Cohort 1 who received B with chemo+H. Participants from Group 1 (TCHB→HB) received: 6 q3w cycles of T (75 mg/m^2) IV + C (6 mg/mL/min) AUC IV, with q3w 1-year of H (8 mg/kg in Cycle 1 and then 6 mg/kg) IV + B (15 mg/kg) IV. Participants from Group 2 (THB→FEC→H) received: 3 q3w cycles of H (8 mg/kg dose 1, 6 mg/kg doses 2 & 3) IV + T (100 mg/m^2 IV) + B (15 mg/kg), then 3 q3w cycles of 5-FU (600 mg/m^2) IV + epirubicin (90 mg/m^2) IV + cyclophosphamide (600 mg/m^2) IV, and then q3w B (15 mg/kg) + H (8 mg/kg dose 4, then 6 mg/kg) IV to complete 1 year of therapy. In this safety cohort, all grades of AEs until 18 months after randomization were collected and are reported in this

    Reporting group title
    Safety Cohort 2: Chemo + Trastuzumab (<18 months)
    Reporting group description
    		 Safety Cohort 2 was set up with participants enrolled after the first 300 participants in each group of chemotherapy which correspond to 2931 participants from Group 1 (non anthracycline regimen [TCH→H or TCHB→HB]). This reporting group included participants in Safety Cohort 2 who received chemo+H but no B, i.e. TCH→H. Participants from Group 1 (TCH→H) received: 6 q3w cycles of T (75 mg/m^2) IV + C (6 mg/mL/min) AUC IV, with q3w 1­year of H (8 mg/kg in Cycle 1 and then 6 mg/kg) IV. In this safety cohort, until 18 months after randomization, only the following adverse events (AEs) were collected: Grade >=2 AE Special Interest (AESI); Grade 1 and 2 AEs requiring change in treatment (i.e. delay in treatment, a dose reduction, or discontinuation of one or more of the study therapy drugs); and all Grade 3 and 4 AE. And they are reported in this reporting group.

    Reporting group title
    Safety Cohort 2: Chemo + Trastuzumab + Bevacizumab(<18 months)
    Reporting group description
    		 Safety Cohort 2 was set up with participants enrolled after the first 300 participants in each group of chemotherapy which correspond to 2931 participants from Group 1 (non anthracycline regimen [TCH→H or TCHB→HB]). This reporting group included participants who received B with chemo+H, i.e. TCHB→HB. Participants from Group 1 (TCHB→HB) received: 6 q3w cycles of T (75 mg/m^2) IV + C (6 mg/mL/min) AUC IV, with q3w 1-year of H (8 mg/kg in Cycle 1 and then 6 mg/kg) IV + B (15 mg/kg) IV. In this safety cohort, until 18 months after randomization, only the following AEs were collected: Grade >=2 AESI; Grade 1 and 2 AEs requiring change in treatment (i.e. delay in treatment, a dose reduction, or discontinuation of one or more of the study therapy drugs); and all Grade 3 and 4 AE. And they are reported in this reporting group.

    Reporting group title
    Chemotherapy + Trastuzumab (>18 months)
    Reporting group description
    		 After 18 months of observation period, the AE collection requirement was the same in both Safety Cohort 1 and 2: Grade >=2 AESI and treatment related Grade 3 and 4 AEs. All collected AEs after 18 months are reported in this reporting group. This reporting group included participants in both Safety Cohort 1 and 2 who received chemo+H but no B, i.e. TCH→H and TH→FEC→H. Participants from Group 1 (TCH→H) received 6 q3w cycles of T (75 mg/m^2) IV + C (6 mg/mL/min) AUC IV, with q3w 1-year of H (8 mg/kg in Cycle 1 and then 6 mg/kg) IV. Participants from Group 2 (TH→FEC→H) received 3 q3w cycles of H (8 mg/kg dose 1, 6 mg/kg doses 2 & 3) IV + T (100 mg/m^2 IV), then 3 q3w cycles of 5-FU (600 mg/m^2) IV + epirubicin (90 mg/m^2) IV + cyclophosphamide (600 mg/m^2) IV, and then H alone q3w (8 mg/kg dose 4, then 6 mg/kg) IV to complete 1 year of therapy.

    Reporting group title
    Chemotherapy + Trastuzumab + Bevacizumab (>18 months)
    Reporting group description
    		 After 18 months observation period, the AE collection requirement was same in both Safety Cohort 1 and 2: Grade >=2 AESI and treatment related Grade 3 and 4 AEs. All collected AEs after 18 months are reported in this reporting group which included participants in Safety Cohort 1 and 2 who received B with chemo+H (TCHB→HB and THB→FEC→HB). Participants from Group 1 (TCHB→HB) received 6 q3w cycles of T (75 mg/m^2) IV + C (6 mg/mL/min) AUC IV, with q3w 1-year of H (8 mg/kg in Cycle 1 and then 6 mg/kg) IV + B (15 mg/kg) IV. Participants from Group 2 (THB→FEC→HB) received 3 q3w cycles of H (8 mg/kg dose 1, 6 mg/kg doses 2 & 3) IV + T (100 mg/m^2 IV) + B (15 mg/kg), then 3 q3w cycles of 5-FU (600 mg/m^2) IV + epirubicin (90 mg/m^2) IV + cyclophosphamide (600 mg/m^2) IV, and then q3w B (15 mg/kg) + H (8 mg/kg dose 4, then 6 mg/kg) IV to complete 1 year of therapy.

    Serious adverse events
    		 Safety Cohort 1: Chemo + Trastuzumab (<18 month) Safety Cohort 1: Chemo + Trastuzumab + Bevacizumab (<18 month) Safety Cohort 2: Chemo + Trastuzumab (<18 months) Safety Cohort 2: Chemo + Trastuzumab + Bevacizumab(<18 months) Chemotherapy + Trastuzumab (>18 months) Chemotherapy + Trastuzumab + Bevacizumab (>18 months)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    64 / 289 (22.15%)
    98 / 286 (34.27%)
    345 / 1461 (23.61%)
    474 / 1436 (33.01%)
    1 / 1750 (0.06%)
    3 / 1722 (0.17%)
         number of deaths (all causes)
    10
    15
    49
    46
    14
    14
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neurilemmoma benign
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carcinoid tumour
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibroadenoma of breast
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemangioma of liver
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 289 (0.35%)
    1 / 286 (0.35%)
    3 / 1461 (0.21%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 4
    2 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    1 / 289 (0.35%)
    1 / 286 (0.35%)
    2 / 1461 (0.14%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 2
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    4 / 1461 (0.27%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    2 / 4
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    5 / 1436 (0.35%)
    0 / 1750 (0.00%)
    1 / 1722 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    5 / 5
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subclavian vein thrombosis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoedema
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Axillary vein thrombosis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Endotracheal intubation
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 289 (0.00%)
    3 / 286 (1.05%)
    2 / 1461 (0.14%)
    7 / 1436 (0.49%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
    2 / 2
    8 / 8
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 289 (0.35%)
    1 / 286 (0.35%)
    1 / 1461 (0.07%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 289 (0.69%)
    0 / 286 (0.00%)
    7 / 1461 (0.48%)
    13 / 1436 (0.91%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    8 / 8
    8 / 13
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device breakage
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 2
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General symptom
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical device complication
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    2 / 1461 (0.14%)
    7 / 1436 (0.49%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    3 / 3
    7 / 7
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombosis in device
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    7 / 1436 (0.49%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    7 / 8
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast complication associated with device
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Discomfort
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Extravasation
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial pain
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulcer haemorrhage
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 289 (0.35%)
    2 / 286 (0.70%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 289 (0.00%)
    2 / 286 (0.70%)
    2 / 1461 (0.14%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 6
    2 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaphylactic reaction
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Adnexa uteri mass
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine haemorrhage
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast calcifications
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mammary fistula
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 289 (0.35%)
    2 / 286 (0.70%)
    0 / 1461 (0.00%)
    4 / 1436 (0.28%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 0
    1 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 289 (0.35%)
    2 / 286 (0.70%)
    3 / 1461 (0.21%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    1 / 3
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 289 (0.00%)
    2 / 286 (0.70%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    5 / 1436 (0.35%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    5 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal oedema
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal septum perforation
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    Aspiration
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphonia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperventilation
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 289 (0.35%)
    2 / 286 (0.70%)
    4 / 1461 (0.27%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 4
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute psychosis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Insomnia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mood altered
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric decompensation
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood creatinine increased
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carbon monoxide diffusing capacity decreased
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lipase
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Seroma
         subjects affected / exposed
    1 / 289 (0.35%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound complication
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia postoperative
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic haematoma
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Cerebrovascular arteriovenous malformation
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    2 / 1461 (0.14%)
    4 / 1436 (0.28%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    2 / 2
    3 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    1 / 1722 (0.06%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleuropericarditis
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    2 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac valve disease
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    1 / 1722 (0.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracardiac thrombus
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Restrictive cardiomyopathy
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Right ventricular dysfunction
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Torsade de pointes
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular arrhythmia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachyarrhythmia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    1 / 1750 (0.06%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 289 (0.00%)
    2 / 286 (0.70%)
    3 / 1461 (0.21%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    1 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    3 / 1461 (0.21%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intercostal neuralgia
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    5 / 1461 (0.34%)
    7 / 1436 (0.49%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    3 / 5
    4 / 7
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    3 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial pressure increased
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sensorimotor disorder
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    18 / 289 (6.23%)
    22 / 286 (7.69%)
    74 / 1461 (5.07%)
    120 / 1436 (8.36%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    18 / 18
    28 / 28
    79 / 79
    124 / 124
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    9 / 289 (3.11%)
    16 / 286 (5.59%)
    54 / 1461 (3.70%)
    84 / 1436 (5.85%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    9 / 9
    17 / 17
    55 / 55
    90 / 90
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    5 / 289 (1.73%)
    0 / 286 (0.00%)
    9 / 1461 (0.62%)
    7 / 1436 (0.49%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
    10 / 10
    6 / 7
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 289 (0.35%)
    2 / 286 (0.70%)
    3 / 1461 (0.21%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    3 / 3
    4 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    7 / 1461 (0.48%)
    12 / 1436 (0.84%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    7 / 7
    12 / 12
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    6 / 1436 (0.42%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    6 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Granulocytopenia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 289 (0.35%)
    1 / 286 (0.35%)
    2 / 1461 (0.14%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Corneal perforation
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dacryostenosis acquired
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eyelid function disorder
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intraocular haematoma
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oscillopsia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    9 / 289 (3.11%)
    7 / 286 (2.45%)
    24 / 1461 (1.64%)
    31 / 1436 (2.16%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    10 / 10
    7 / 8
    26 / 30
    31 / 36
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    4 / 289 (1.38%)
    3 / 286 (1.05%)
    14 / 1461 (0.96%)
    20 / 1436 (1.39%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    5 / 5
    4 / 4
    14 / 14
    20 / 23
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    3 / 289 (1.04%)
    2 / 286 (0.70%)
    6 / 1461 (0.41%)
    6 / 1436 (0.42%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 3
    7 / 7
    6 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 289 (0.00%)
    3 / 286 (1.05%)
    3 / 1461 (0.21%)
    9 / 1436 (0.63%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    2 / 3
    6 / 11
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 289 (0.00%)
    2 / 286 (0.70%)
    1 / 1461 (0.07%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 289 (0.00%)
    2 / 286 (0.70%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    2 / 1461 (0.14%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 2
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric perforation
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    4 / 1436 (0.28%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    3 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroduodenal ulcer
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal ulcer
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    2 / 1461 (0.14%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    5 / 1436 (0.35%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 2
    5 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    3 / 1461 (0.21%)
    4 / 1436 (0.28%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 3
    3 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    3 / 1461 (0.21%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    3 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal haemorrhage
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal distension
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer perforation
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal toxicity
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic colitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disease
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cold sweat
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nail disorder
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain of skin
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash generalised
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash pruritic
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash vesicular
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin atrophy
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin disorder
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin exfoliation
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 289 (0.35%)
    1 / 286 (0.35%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    2 / 289 (0.69%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus ureteric
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glomerulosclerosis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prerenal failure
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Inappropriate antidiuretic hormone secretion
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    2 / 1461 (0.14%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scleroderma
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Neutropenic infection
         subjects affected / exposed
    0 / 289 (0.00%)
    8 / 286 (2.80%)
    33 / 1461 (2.26%)
    45 / 1436 (3.13%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    8 / 8
    31 / 34
    44 / 46
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 289 (0.35%)
    6 / 286 (2.10%)
    11 / 1461 (0.75%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 6
    2 / 11
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 289 (0.69%)
    1 / 286 (0.35%)
    5 / 1461 (0.34%)
    6 / 1436 (0.42%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 6
    4 / 6
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 289 (0.35%)
    2 / 286 (0.70%)
    6 / 1461 (0.41%)
    13 / 1436 (0.91%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 6
    3 / 13
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 289 (0.00%)
    2 / 286 (0.70%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 289 (0.35%)
    1 / 286 (0.35%)
    4 / 1461 (0.27%)
    10 / 1436 (0.70%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    3 / 4
    6 / 10
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 289 (0.35%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 289 (0.35%)
    1 / 286 (0.35%)
    5 / 1461 (0.34%)
    8 / 1436 (0.56%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 1
    3 / 5
    3 / 8
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 289 (0.35%)
    1 / 286 (0.35%)
    4 / 1461 (0.27%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    2 / 4
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute tonsillitis
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    1 / 1461 (0.07%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    3 / 1461 (0.21%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    2 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    4 / 1461 (0.27%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    3 / 4
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected cyst
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Kidney infection
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mastitis
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    2 / 1461 (0.14%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 2
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    2 / 1461 (0.14%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salmonellosis
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    0 / 1461 (0.00%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    4 / 1461 (0.27%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    3 / 1461 (0.21%)
    4 / 1436 (0.28%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    4 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Infectious colitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    4 / 1436 (0.28%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    3 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    3 / 1461 (0.21%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    3 / 1461 (0.21%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blister infected
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis staphylococcal
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal sepsis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute sinusitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blastocystis infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cellulitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes virus infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paronychia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periodontitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonsillitis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia escherichia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctitis infectious
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal bacteraemia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonas infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rickettsiosis
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal skin infection
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 289 (0.69%)
    4 / 286 (1.40%)
    9 / 1461 (0.62%)
    10 / 1436 (0.70%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 4
    7 / 9
    17 / 17
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    2 / 1461 (0.14%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    2 / 4
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 289 (0.35%)
    0 / 286 (0.00%)
    3 / 1461 (0.21%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    3 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 289 (0.00%)
    1 / 286 (0.35%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    2 / 1461 (0.14%)
    5 / 1436 (0.35%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    4 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    0 / 1461 (0.00%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 289 (0.00%)
    0 / 286 (0.00%)
    1 / 1461 (0.07%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Safety Cohort 1: Chemo + Trastuzumab (<18 month) Safety Cohort 1: Chemo + Trastuzumab + Bevacizumab (<18 month) Safety Cohort 2: Chemo + Trastuzumab (<18 months) Safety Cohort 2: Chemo + Trastuzumab + Bevacizumab(<18 months) Chemotherapy + Trastuzumab (>18 months) Chemotherapy + Trastuzumab + Bevacizumab (>18 months)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    278 / 289 (96.19%)
    271 / 286 (94.76%)
    950 / 1461 (65.02%)
    989 / 1436 (68.87%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    68 / 289 (23.53%)
    58 / 286 (20.28%)
    16 / 1461 (1.10%)
    20 / 1436 (1.39%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    71
    60
    16
    21
    0
    0
    Lymphoedema
         subjects affected / exposed
    18 / 289 (6.23%)
    16 / 286 (5.59%)
    4 / 1461 (0.27%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    19
    17
    4
    3
    0
    0
    Flushing
         subjects affected / exposed
    16 / 289 (5.54%)
    11 / 286 (3.85%)
    3 / 1461 (0.21%)
    5 / 1436 (0.35%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    18
    12
    4
    5
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    147 / 289 (50.87%)
    162 / 286 (56.64%)
    128 / 1461 (8.76%)
    103 / 1436 (7.17%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    183
    184
    169
    149
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    69 / 289 (23.88%)
    85 / 286 (29.72%)
    30 / 1461 (2.05%)
    51 / 1436 (3.55%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    99
    112
    33
    57
    0
    0
    Asthenia
         subjects affected / exposed
    49 / 289 (16.96%)
    38 / 286 (13.29%)
    49 / 1461 (3.35%)
    52 / 1436 (3.62%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    78
    62
    56
    58
    0
    0
    Pyrexia
         subjects affected / exposed
    28 / 289 (9.69%)
    47 / 286 (16.43%)
    17 / 1461 (1.16%)
    18 / 1436 (1.25%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    36
    57
    18
    19
    0
    0
    Oedema peripheral
         subjects affected / exposed
    46 / 289 (15.92%)
    27 / 286 (9.44%)
    25 / 1461 (1.71%)
    4 / 1436 (0.28%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    54
    31
    27
    4
    0
    0
    Oedema
         subjects affected / exposed
    25 / 289 (8.65%)
    15 / 286 (5.24%)
    7 / 1461 (0.48%)
    0 / 1436 (0.00%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    28
    17
    7
    0
    0
    0
    Pain
         subjects affected / exposed
    20 / 289 (6.92%)
    18 / 286 (6.29%)
    8 / 1461 (0.55%)
    1 / 1436 (0.07%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    23
    19
    8
    1
    0
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    17 / 289 (5.88%)
    16 / 286 (5.59%)
    34 / 1461 (2.33%)
    31 / 1436 (2.16%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    22
    21
    41
    35
    0
    0
    Reproductive system and breast disorders
    Menstruation irregular
         subjects affected / exposed
    22 / 289 (7.61%)
    18 / 286 (6.29%)
    100 / 1461 (6.84%)
    97 / 1436 (6.75%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    23
    18
    102
    98
    0
    0
    Breast pain
         subjects affected / exposed
    12 / 289 (4.15%)
    15 / 286 (5.24%)
    2 / 1461 (0.14%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    14
    19
    2
    2
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    35 / 289 (12.11%)
    116 / 286 (40.56%)
    12 / 1461 (0.82%)
    83 / 1436 (5.78%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    36
    133
    12
    100
    0
    0
    Cough
         subjects affected / exposed
    56 / 289 (19.38%)
    49 / 286 (17.13%)
    3 / 1461 (0.21%)
    10 / 1436 (0.70%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    59
    53
    3
    11
    0
    0
    Dyspnoea
         subjects affected / exposed
    45 / 289 (15.57%)
    40 / 286 (13.99%)
    17 / 1461 (1.16%)
    12 / 1436 (0.84%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    50
    42
    18
    14
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    21 / 289 (7.27%)
    36 / 286 (12.59%)
    3 / 1461 (0.21%)
    6 / 1436 (0.42%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    27
    43
    3
    7
    0
    0
    Respiratory tract haemorrhage
         subjects affected / exposed
    3 / 289 (1.04%)
    20 / 286 (6.99%)
    0 / 1461 (0.00%)
    9 / 1436 (0.63%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    3
    24
    0
    10
    0
    0
    Dysphonia
         subjects affected / exposed
    5 / 289 (1.73%)
    17 / 286 (5.94%)
    1 / 1461 (0.07%)
    5 / 1436 (0.35%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    5
    18
    1
    6
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    61 / 289 (21.11%)
    58 / 286 (20.28%)
    13 / 1461 (0.89%)
    9 / 1436 (0.63%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    64
    64
    13
    9
    0
    0
    Anxiety
         subjects affected / exposed
    31 / 289 (10.73%)
    22 / 286 (7.69%)
    8 / 1461 (0.55%)
    5 / 1436 (0.35%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    34
    22
    8
    5
    0
    0
    Depression
         subjects affected / exposed
    23 / 289 (7.96%)
    20 / 286 (6.99%)
    6 / 1461 (0.41%)
    6 / 1436 (0.42%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    24
    21
    6
    6
    0
    0
    Investigations
    Weight decreased
         subjects affected / exposed
    15 / 289 (5.19%)
    36 / 286 (12.59%)
    2 / 1461 (0.14%)
    10 / 1436 (0.70%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    15
    37
    2
    11
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    15 / 289 (5.19%)
    17 / 286 (5.94%)
    28 / 1461 (1.92%)
    29 / 1436 (2.02%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    18
    22
    32
    35
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    16 / 289 (5.54%)
    10 / 286 (3.50%)
    22 / 1461 (1.51%)
    14 / 1436 (0.97%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    18
    12
    25
    19
    0
    0
    Injury, poisoning and procedural complications
    Radiation skin injury
         subjects affected / exposed
    39 / 289 (13.49%)
    34 / 286 (11.89%)
    8 / 1461 (0.55%)
    12 / 1436 (0.84%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    39
    36
    8
    13
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    63 / 289 (21.80%)
    90 / 286 (31.47%)
    25 / 1461 (1.71%)
    30 / 1436 (2.09%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    76
    108
    27
    34
    0
    0
    Dysgeusia
         subjects affected / exposed
    60 / 289 (20.76%)
    72 / 286 (25.17%)
    14 / 1461 (0.96%)
    6 / 1436 (0.42%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    72
    78
    15
    6
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    59 / 289 (20.42%)
    61 / 286 (21.33%)
    56 / 1461 (3.83%)
    80 / 1436 (5.57%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    68
    72
    61
    83
    0
    0
    Dizziness
         subjects affected / exposed
    46 / 289 (15.92%)
    37 / 286 (12.94%)
    15 / 1461 (1.03%)
    9 / 1436 (0.63%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    58
    48
    15
    9
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    32 / 289 (11.07%)
    31 / 286 (10.84%)
    33 / 1461 (2.26%)
    41 / 1436 (2.86%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    37
    34
    39
    44
    0
    0
    Paraesthesia
         subjects affected / exposed
    10 / 289 (3.46%)
    21 / 286 (7.34%)
    10 / 1461 (0.68%)
    11 / 1436 (0.77%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    10
    23
    11
    12
    0
    0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    103 / 289 (35.64%)
    84 / 286 (29.37%)
    343 / 1461 (23.48%)
    315 / 1436 (21.94%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    165
    113
    672
    604
    0
    0
    Anaemia
         subjects affected / exposed
    89 / 289 (30.80%)
    80 / 286 (27.97%)
    198 / 1461 (13.55%)
    127 / 1436 (8.84%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    108
    86
    218
    134
    0
    0
    Leukopenia
         subjects affected / exposed
    63 / 289 (21.80%)
    46 / 286 (16.08%)
    122 / 1461 (8.35%)
    101 / 1436 (7.03%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    106
    58
    215
    175
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    33 / 289 (11.42%)
    41 / 286 (14.34%)
    164 / 1461 (11.23%)
    135 / 1436 (9.40%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    52
    51
    227
    174
    0
    0
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    30 / 289 (10.38%)
    52 / 286 (18.18%)
    4 / 1461 (0.27%)
    14 / 1436 (0.97%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    33
    55
    7
    15
    0
    0
    Vision blurred
         subjects affected / exposed
    17 / 289 (5.88%)
    10 / 286 (3.50%)
    5 / 1461 (0.34%)
    2 / 1436 (0.14%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    17
    13
    5
    2
    0
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    179 / 289 (61.94%)
    170 / 286 (59.44%)
    104 / 1461 (7.12%)
    95 / 1436 (6.62%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    274
    248
    129
    118
    0
    0
    Diarrhoea
         subjects affected / exposed
    136 / 289 (47.06%)
    163 / 286 (56.99%)
    148 / 1461 (10.13%)
    148 / 1436 (10.31%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    180
    221
    177
    175
    0
    0
    Vomiting
         subjects affected / exposed
    90 / 289 (31.14%)
    93 / 286 (32.52%)
    61 / 1461 (4.18%)
    56 / 1436 (3.90%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    118
    119
    68
    66
    0
    0
    Constipation
         subjects affected / exposed
    87 / 289 (30.10%)
    84 / 286 (29.37%)
    25 / 1461 (1.71%)
    25 / 1436 (1.74%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    101
    96
    26
    28
    0
    0
    Stomatitis
         subjects affected / exposed
    52 / 289 (17.99%)
    77 / 286 (26.92%)
    37 / 1461 (2.53%)
    46 / 1436 (3.20%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    65
    90
    44
    53
    0
    0
    Dyspepsia
         subjects affected / exposed
    46 / 289 (15.92%)
    53 / 286 (18.53%)
    20 / 1461 (1.37%)
    13 / 1436 (0.91%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    54
    58
    21
    13
    0
    0
    Abdominal pain
         subjects affected / exposed
    32 / 289 (11.07%)
    36 / 286 (12.59%)
    24 / 1461 (1.64%)
    22 / 1436 (1.53%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    43
    50
    28
    22
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    21 / 289 (7.27%)
    26 / 286 (9.09%)
    12 / 1461 (0.82%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    26
    29
    14
    3
    0
    0
    Haemorrhoids
         subjects affected / exposed
    8 / 289 (2.77%)
    20 / 286 (6.99%)
    4 / 1461 (0.27%)
    16 / 1436 (1.11%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    9
    21
    4
    16
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    182 / 289 (62.98%)
    175 / 286 (61.19%)
    95 / 1461 (6.50%)
    91 / 1436 (6.34%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    190
    181
    97
    93
    0
    0
    Nail disorder
         subjects affected / exposed
    60 / 289 (20.76%)
    83 / 286 (29.02%)
    4 / 1461 (0.27%)
    15 / 1436 (1.04%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    61
    86
    5
    15
    0
    0
    Rash
         subjects affected / exposed
    73 / 289 (25.26%)
    59 / 286 (20.63%)
    28 / 1461 (1.92%)
    21 / 1436 (1.46%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    85
    66
    28
    23
    0
    0
    Dry skin
         subjects affected / exposed
    20 / 289 (6.92%)
    31 / 286 (10.84%)
    2 / 1461 (0.14%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    21
    33
    2
    3
    0
    0
    Pruritus
         subjects affected / exposed
    31 / 289 (10.73%)
    18 / 286 (6.29%)
    3 / 1461 (0.21%)
    4 / 1436 (0.28%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    36
    20
    3
    5
    0
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    17 / 289 (5.88%)
    23 / 286 (8.04%)
    6 / 1461 (0.41%)
    12 / 1436 (0.84%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    23
    24
    7
    13
    0
    0
    Erythema
         subjects affected / exposed
    15 / 289 (5.19%)
    15 / 286 (5.24%)
    5 / 1461 (0.34%)
    4 / 1436 (0.28%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    22
    17
    5
    5
    0
    0
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    4 / 289 (1.38%)
    39 / 286 (13.64%)
    9 / 1461 (0.62%)
    94 / 1436 (6.55%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    4
    45
    9
    111
    0
    0
    Dysuria
         subjects affected / exposed
    17 / 289 (5.88%)
    17 / 286 (5.94%)
    4 / 1461 (0.27%)
    4 / 1436 (0.28%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    20
    22
    4
    4
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    69 / 289 (23.88%)
    80 / 286 (27.97%)
    47 / 1461 (3.22%)
    56 / 1436 (3.90%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    85
    99
    55
    58
    0
    0
    Myalgia
         subjects affected / exposed
    58 / 289 (20.07%)
    67 / 286 (23.43%)
    31 / 1461 (2.12%)
    19 / 1436 (1.32%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    93
    90
    40
    21
    0
    0
    Bone pain
         subjects affected / exposed
    39 / 289 (13.49%)
    45 / 286 (15.73%)
    24 / 1461 (1.64%)
    20 / 1436 (1.39%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    49
    49
    33
    21
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    27 / 289 (9.34%)
    39 / 286 (13.64%)
    15 / 1461 (1.03%)
    31 / 1436 (2.16%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    38
    40
    16
    35
    0
    0
    Back pain
         subjects affected / exposed
    29 / 289 (10.03%)
    35 / 286 (12.24%)
    15 / 1461 (1.03%)
    10 / 1436 (0.70%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    37
    36
    15
    12
    0
    0
    Pain in extremity
         subjects affected / exposed
    21 / 289 (7.27%)
    38 / 286 (13.29%)
    4 / 1461 (0.27%)
    16 / 1436 (1.11%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    27
    42
    4
    18
    0
    0
    Muscle spasms
         subjects affected / exposed
    16 / 289 (5.54%)
    7 / 286 (2.45%)
    2 / 1461 (0.14%)
    3 / 1436 (0.21%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    18
    8
    3
    3
    0
    0
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    39 / 289 (13.49%)
    38 / 286 (13.29%)
    24 / 1461 (1.64%)
    19 / 1436 (1.32%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    46
    43
    24
    20
    0
    0
    Urinary tract infection
         subjects affected / exposed
    22 / 289 (7.61%)
    45 / 286 (15.73%)
    24 / 1461 (1.64%)
    28 / 1436 (1.95%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    24
    55
    30
    29
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    18 / 289 (6.23%)
    29 / 286 (10.14%)
    6 / 1461 (0.41%)
    10 / 1436 (0.70%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    26
    38
    6
    10
    0
    0
    Rhinitis
         subjects affected / exposed
    20 / 289 (6.92%)
    27 / 286 (9.44%)
    0 / 1461 (0.00%)
    4 / 1436 (0.28%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    20
    29
    0
    4
    0
    0
    Infection
         subjects affected / exposed
    8 / 289 (2.77%)
    15 / 286 (5.24%)
    12 / 1461 (0.82%)
    16 / 1436 (1.11%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    8
    16
    13
    19
    0
    0
    Cystitis
         subjects affected / exposed
    5 / 289 (1.73%)
    16 / 286 (5.59%)
    8 / 1461 (0.55%)
    5 / 1436 (0.35%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    11
    17
    9
    5
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    63 / 289 (21.80%)
    63 / 286 (22.03%)
    13 / 1461 (0.89%)
    16 / 1436 (1.11%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    71
    75
    16
    19
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    14 / 289 (4.84%)
    19 / 286 (6.64%)
    13 / 1461 (0.89%)
    10 / 1436 (0.70%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    16
    23
    13
    10
    0
    0
    Hypokalaemia
         subjects affected / exposed
    17 / 289 (5.88%)
    13 / 286 (4.55%)
    27 / 1461 (1.85%)
    19 / 1436 (1.32%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    18
    13
    30
    21
    0
    0
    Dehydration
         subjects affected / exposed
    13 / 289 (4.50%)
    15 / 286 (5.24%)
    4 / 1461 (0.27%)
    13 / 1436 (0.91%)
    0 / 1750 (0.00%)
    0 / 1722 (0.00%)
         occurrences all number
    17
    15
    4
    14
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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.
    The study was terminated prematurely as there were no efficacy benefits accrued to participants with use of bevacizumab and there were no new safety concerns found when examining the study data.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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