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    Clinical Trial Results:
    A Multicenter, Phase III, Open-Label, Randomized Study in Previously Untreated Patients With Advanced Indolent Non-Hodgkin's Lymphoma Evaluating the Benefit of GA101 (RO5072759) Plus Chemotherapy Compared with Rituximab Plus Chemotherapy Followed by GA101 or Rituximab Maintenance Therapy in Responders

    Summary
    EudraCT number
    		 2010-024132-41
    Trial protocol
    		 BE   GB   CZ   SE   DE   HU   FR   ES   IT   FI  
    Global end of trial date

    Results information
    Results version number
    		 v1
    This version publication date
    16 Mar 2017
    First version publication date
    16 Mar 2017
    Other versions
    		 v2 , v3

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    BO21223
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01332968
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Study name: GALLIUM
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, 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
    Interim
    Date of interim/final analysis
    31 Jan 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Jan 2016
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of obinutuzumab (RO5072759) in combination with chemotherapy compared to rituximab (MabThera/Rituxan) with chemotherapy followed by obinutuzumab or rituximab maintenance in subjects with previously untreated advanced follicular non-Hodgkin's lymphoma.
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Jul 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy
    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
    China: 58
    Country: Number of subjects enrolled
    Japan: 129
    Country: Number of subjects enrolled
    Taiwan: 4
    Country: Number of subjects enrolled
    Czech Republic: 100
    Country: Number of subjects enrolled
    Hungary: 71
    Country: Number of subjects enrolled
    Russian Federation: 12
    Country: Number of subjects enrolled
    Canada: 138
    Country: Number of subjects enrolled
    United States: 31
    Country: Number of subjects enrolled
    Australia: 136
    Country: Number of subjects enrolled
    Israel: 6
    Country: Number of subjects enrolled
    Belgium: 35
    Country: Number of subjects enrolled
    Germany: 237
    Country: Number of subjects enrolled
    Spain: 48
    Country: Number of subjects enrolled
    Finland: 4
    Country: Number of subjects enrolled
    France: 30
    Country: Number of subjects enrolled
    United Kingdom: 293
    Country: Number of subjects enrolled
    Italy: 59
    Country: Number of subjects enrolled
    Sweden: 10
    Worldwide total number of subjects
    1401
    EEA total number of subjects
    887
    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)
    937
    From 65 to 84 years
    454
    85 years and over
    10

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Eleven patients withdrew from the study after randomization but prior to receiving study treatment.

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Rituximab+Chemotherapy – Induction
    Arm description
    		 Subjects received either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during induction period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual subject was chosen by the site prior to initiation of the study.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cyclophosphamide 750 milligrams per square metre (mg/m^2) will be administered intravenously (IV) on Day 1 of each cycle during induction period.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 50 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vincristine 1.4 mg/m^2 (maximum 2 mg) IV will be administered on Day 1 of each cycle during induction period.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Prednisone 100 mg (or equivalent prednisolone or methylprednisolone) will be administered orally on Days 1-5 of each cycle during induction period

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bendamustine 90 mg/m^2 IV infusion will be administered on Days 1 and 2 of each cycle during induction period.

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    MabThera/Rituxan
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Rituximab 375 mg/m^2 IV infusion will be administered on Day 1 of each cycle during induction period and rituximab 375 mg/m^2 every 2 months during maintenance period.

    Arm title
    		 Obinutuzumab+Chemotherapy – Induction
    Arm description
    		 Subjects received either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual subject was chosen by the site prior to initiation of the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    GA101; RO5072759
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Obinutuzumab 1000 mg IV infusion will be administered on Day 1, 8, and 15 of Cycle 1 and then on Day 1 of each subsequent cycle during induction period and obinutuzumab 1000 mg IV infusion every 2 months during maintenance period.

    Investigational medicinal product name
    Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cyclophosphamide 750 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Doxorubicin 50 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.

    Investigational medicinal product name
    Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vincristine 1.4 mg/m^2 (maximum 2 mg) IV will be administered on Day 1 of each cycle during induction period.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Prednisone 100 mg (or equivalent prednisolone or methylprednisolone) will be administered orally on Days 1-5 of each cycle during induction period

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Bendamustine 90 mg/m^2 IV infusion will be administered on Days 1 and 2 of each cycle during induction period.

    Arm title
    		 Rituximab+Chemotherapy – Maintenance
    Arm description
    		 The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received rituximab monotherapy every 2 months for 2 years during the maintenance period.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    MabThera/Rituxan
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Rituximab 375 mg/m^2 IV infusion will be administered on Day 1 of each cycle during induction period and rituximab 375 mg/m^2 every 2 months during maintenance period.

    Arm title
    		 Obinutuzumab+Chemotherapy – Maintenance
    Arm description
    		 The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received obinutuzumab monotherapy every 2 months for 2 years during the maintenance period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    GA101; RO5072759
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Obinutuzumab 1000 mg IV infusion will be administered on Day 1, 8, and 15 of Cycle 1 and then on Day 1 of each subsequent cycle during induction period and obinutuzumab 1000 mg IV infusion every 2 months during maintenance period.

    Arm title
    		 Rituximab+Chemotherapy – Observation
    Arm description
    		 The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Non-responders received no protocol specified treatment during the 2-year observation period.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    MabThera/Rituxan
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Rituximab 375 mg/m^2 IV infusion will be administered on Day 1 of each cycle during induction period and rituximab 375 mg/m^2 every 2 months during maintenance period.

    Arm title
    		 Obinutuzumab+Chemotherapy – Observation
    Arm description
    		 The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Non-responders received no protocol specified treatment during the 2-year observation period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    GA101; RO5072759
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Obinutuzumab 1000 mg IV infusion will be administered on Day 1, 8, and 15 of Cycle 1 and then on Day 1 of each subsequent cycle during induction period and obinutuzumab 1000 mg IV infusion every 2 months during maintenance period.

    Arm title
    		 Rituximab+Chemotherapy – Follow-up
    Arm description
    		 Finally, subjects were followed during a 5-year follow-up period.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    MabThera/Rituxan
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Rituximab 375 mg/m^2 IV infusion will be administered on Day 1 of each cycle during induction period and rituximab 375 mg/m^2 every 2 months during maintenance period.

    Arm title
    		 Obinutuzumab+Chemotherapy – Follow-up
    Arm description
    		 Finally, subjects were followed during a 5-year follow-up period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    GA101; RO5072759
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Obinutuzumab 1000 mg IV infusion will be administered on Day 1, 8, and 15 of Cycle 1 and then on Day 1 of each subsequent cycle during induction period and obinutuzumab 1000 mg IV infusion every 2 months during maintenance period.

    Number of subjects in period 1
    		Rituximab+Chemotherapy – Induction Obinutuzumab+Chemotherapy – Induction Rituximab+Chemotherapy – Maintenance Obinutuzumab+Chemotherapy – Maintenance Rituximab+Chemotherapy – Observation Obinutuzumab+Chemotherapy – Observation Rituximab+Chemotherapy – Follow-up Obinutuzumab+Chemotherapy – Follow-up
    Started
    699
    702
    612
    624
    12
    11
    542
    531
    Completed
    641
    646
    399
    417
    2
    2
    0
    0
    Not completed
    58
    56
    213
    207
    10
    9
    542
    531
         Physician decision
    6
    1
    14
    19
    -
    -
    -
    -
         Adverse Event
    23
    26
    50
    65
    -
    -
    -
    -
         Death
    1
    4
    5
    6
    -
    -
    38
    22
         Progressive Disease
    15
    7
    72
    39
    -
    -
    -
    -
         Other Reason
    2
    2
    4
    5
    -
    -
    -
    -
         Ongoing
    -
    -
    54
    62
    10
    8
    502
    505
         Non-compliance
    1
    -
    2
    3
    -
    1
    -
    -
         Randomised but not treated
    4
    7
    -
    -
    -
    -
    -
    -
         Withdrawal by Subject
    3
    5
    10
    5
    -
    -
    1
    2
         Lost to follow-up
    -
    -
    1
    2
    -
    -
    1
    2
         Protocol deviation
    3
    4
    1
    1
    -
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Period
    Reporting group description
    		 -

    Reporting group values
    		 Overall Period Total
    Number of subjects
    		 1401 1401
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    		 937 937
        From 65-84 years
    		 454 454
        85 years and over
    		 10 10
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 58.5 ± 11.9 -
    Gender Categorical
    Units: Subjects
        Female
    		 739 739
        Male
    		 662 662
    Age Continuous in Follicular Lymphoma Sub-Population
    Age continuous for subjects with follicular lymphoma, who encompassed the population for the primary endpoint (n=601 for each arm in the follicular lymphoma intent-to-treat population).
    Units: years
        arithmetic mean (standard deviation)
    		 57.9 ± 11.9 -
    Subject analysis sets

    Subject analysis set title
    Rituximab+Chemotherapy
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects received either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, subjects were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual subject was chosen by the site prior to initiation of the study.

    Subject analysis set title
    Obinutuzumab+Chemotherapy
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects received either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, subjects were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual subject was chosen by the site prior to initiation of the study.

    Subject analysis sets values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects
    699
    702
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    473
    464
        From 65-84 years
    221
    233
        85 years and over
    5
    5
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    58.1 ± 12.3
    58.9 ± 11.6
    Gender Categorical
    Units: Subjects
        Female
    374
    365
        Male
    325
    337
    Age Continuous in Follicular Lymphoma Sub-Population
    Age continuous for subjects with follicular lymphoma, who encompassed the population for the primary endpoint (n=601 for each arm in the follicular lymphoma intent-to-treat population).
    Units: years
        arithmetic mean (standard deviation)
    57.7 ± 12.2
    58.2 ± 11.5

    End points

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    End points reporting groups
    Reporting group title
    Rituximab+Chemotherapy – Induction
    Reporting group description
    		 Subjects received either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during induction period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual subject was chosen by the site prior to initiation of the study.

    Reporting group title
    Obinutuzumab+Chemotherapy – Induction
    Reporting group description
    		 Subjects received either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual subject was chosen by the site prior to initiation of the study.

    Reporting group title
    Rituximab+Chemotherapy – Maintenance
    Reporting group description
    		 The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received rituximab monotherapy every 2 months for 2 years during the maintenance period.

    Reporting group title
    Obinutuzumab+Chemotherapy – Maintenance
    Reporting group description
    		 The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received obinutuzumab monotherapy every 2 months for 2 years during the maintenance period.

    Reporting group title
    Rituximab+Chemotherapy – Observation
    Reporting group description
    		 The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Non-responders received no protocol specified treatment during the 2-year observation period.

    Reporting group title
    Obinutuzumab+Chemotherapy – Observation
    Reporting group description
    		 The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Non-responders received no protocol specified treatment during the 2-year observation period.

    Reporting group title
    Rituximab+Chemotherapy – Follow-up
    Reporting group description
    		 Finally, subjects were followed during a 5-year follow-up period.

    Reporting group title
    Obinutuzumab+Chemotherapy – Follow-up
    Reporting group description
    		 Finally, subjects were followed during a 5-year follow-up period.

    Subject analysis set title
    Rituximab+Chemotherapy
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects received either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, subjects were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual subject was chosen by the site prior to initiation of the study.

    Subject analysis set title
    Obinutuzumab+Chemotherapy
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subjects received either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, subjects were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual subject was chosen by the site prior to initiation of the study.

    Primary: Progression-Free Survival (PFS) in the Follicular Lymphoma Population, Investigator-Assessed

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    End point title
    		 Progression-Free Survival (PFS) in the Follicular Lymphoma Population, Investigator-Assessed
    End point description
    PFS in subjects with follicular lymphoma was defined as the time from randomisation until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimetre (cm) or >/= 50% increase in other target measurable lesions and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumour measurements were obtained by computed tomography (CT) or magnetic resonance imaging (MRI). The intent-to-treat follicular lymphoma population (FL ITT) was defined as all randomised subjects with follicular histology grouped according to treatment arm regardless of what treatments were actually received.
    End point type
    Primary
    End point timeframe
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: percentage of subjects with event
        number (not applicable)
    24
    16.8
    Statistical analysis title
    		 Rituximab versus Obinutuzumab
    Comparison groups
    Rituximab+Chemotherapy v Obinutuzumab+Chemotherapy
    Number of subjects included in analysis
    1202
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0012 [1]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 0.85
    Notes
    [1] - Stratified by chemotherapy regimen and Follicular Lymphoma International Prognostic Index (FLIPI) risk group.

    Secondary: Progression-Free Survival in the Overall Study Population, Investigator-Assessed

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    End point title
    		 Progression-Free Survival in the Overall Study Population, Investigator-Assessed
    End point description
    PFS in the overall study population was defined as the time from randomisation until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumour measurements were obtained by CT/MRI. The ITT population was defined as all randomised subjects grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    699
    702
    Units: percentage of subjects with event
        number (not applicable)
    24.5
    17.4
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS) (Overall Study Population), Assessed by Independent Review Committee (IRC)

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    End point title
    		 Progression-Free Survival (PFS) (Overall Study Population), Assessed by Independent Review Committee (IRC)
    End point description
    PFS in the overall study population was defined as the time from randomisation until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of IRC assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumour measurements were obtained by CT/MRI. The ITT population was defined as all randomised subjects grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    699
    702
    Units: percentage of subjects with event
        number (not applicable)
    21.6
    16.1
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS) (Follicular Lymphoma Population), IRC-Assessed

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    End point title
    		 Progression-Free Survival (PFS) (Follicular Lymphoma Population), IRC-Assessed
    End point description
    PFS in the subjects with follicular lymphoma was defined as the time from randomisation until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of IRC assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumour measurements were obtained by CT/MRI. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: percentage of subjects with event
        number (not applicable)
    20.8
    15.5
    No statistical analyses for this end point

    Secondary: Overall Response (Overall Study Population), Investigator-Assessed

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    End point title
    		 Overall Response (Overall Study Population), Investigator-Assessed
    End point description
    Percentage of subjects with overall response in the overall study population was defined as percentage of subjects with partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumour assessments were performed with CT/MRI with or without positron emission tomography (PET). CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%; Overall Response (OR) = CR + PR. The ITT population was defined as all randomised subjects grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of induction period (up to approximately 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    699
    702
    Units: percentage of subjects with event
    number (not applicable)
        Without PET
    86.1
    87.6
        With PET
    82.1
    85.7
    No statistical analyses for this end point

    Secondary: Overall Response (Follicular Lymphoma Population), Investigator-Assessed

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    End point title
    		 Overall Response (Follicular Lymphoma Population), Investigator-Assessed
    End point description
    Percentage of subjects with overall response in the follicular lymphoma population was defined as percentage of subjects with PR or complete response CR determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumour assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Overall Response (OR) = CR + PR. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of induction period (up to approximately 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: percentage of subjects with event
    number (not applicable)
        Without PET
    86.9
    88.5
        With PET
    81.5
    85.9
    No statistical analyses for this end point

    Secondary: Complete Response (Overall Study Population), Investigator-Assessed

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    End point title
    		 Complete Response (Overall Study Population), Investigator-Assessed
    End point description
    Complete response in the overall study population was determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions. The ITT population was defined as all randomised subjects grouped according to their randomised treatment arm regardless of what treatments were actually received. Reported is the percentage of subjects with event.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of induction period (up to approximately 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    699
    702
    Units: percentage of subjects with event
    number (not applicable)
        Without PET
    23.2
    18.9
        With PET
    57.3
    61.4
    No statistical analyses for this end point

    Secondary: Complete Response (Follicular Lymphoma Population), Investigator-Assessed

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    End point title
    		 Complete Response (Follicular Lymphoma Population), Investigator-Assessed
    End point description
    Complete response in the follicular lymphoma population was determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumour assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of induction period (up to approximately 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: percentage of subjects with event
    number (not applicable)
        Without PET
    23.8
    19.5
        With PET
    56.7
    62.3
    No statistical analyses for this end point

    Secondary: Overall Response (Overall Study Population), IRC-Assessed

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    End point title
    		 Overall Response (Overall Study Population), IRC-Assessed
    End point description
    Percentage of subjects with overall response in the overall study population was defined as percentage of subjects with PR or CR determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumour assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%; Overall Response (OR) = CR + PR. The ITT population was defined as all randomised subjects grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of induction period (up to approximately 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    699
    702
    Units: percentage of subjects with event
    number (not applicable)
        Without PET
    86.7
    89.7
        With PET
    83.3
    87.2
    No statistical analyses for this end point

    Secondary: Overall Response (Follicular Lymphoma Population), IRC-Assessed

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    End point title
    		 Overall Response (Follicular Lymphoma Population), IRC-Assessed
    End point description
    Percentage of subjects with overall response in the follicular lymphoma population was defined as percentage of subjects with PR or complete response CR determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumour assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Overall Response (OR) = CR + PR. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of induction period (up to approximately 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: percentage of subjects with event
    number (not applicable)
        Without PET
    88
    91.2
        With PET
    85.2
    88.6
    No statistical analyses for this end point

    Secondary: Complete Response (Overall Study Population), IRC-Assessed

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    End point title
    		 Complete Response (Overall Study Population), IRC-Assessed
    End point description
    Complete response in the overall study population was determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumour assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions. The ITT population was defined as all randomised subjects grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of induction period (up to approximately 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    699
    702
    Units: percentage of subjects with event
    number (not applicable)
        Without PET
    25.9
    26.9
        With PET
    59.4
    69.5
    No statistical analyses for this end point

    Secondary: Complete Response (Follicular Lymphoma Population), IRC-Assessed

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    End point title
    		 Complete Response (Follicular Lymphoma Population), IRC-Assessed
    End point description
    Complete response in the follicular lymphoma population was determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumour assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of induction period (up to approximately 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: percentage of subjects with event
    number (not applicable)
        Without PET
    26.5
    28.5
        With PET
    59.7
    71.4
    No statistical analyses for this end point

    Secondary: Overall Survival (Overall Study Population)

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    End point title
    		 Overall Survival (Overall Study Population)
    End point description
    Overall survival in the overall study population was defined as the time from the date of randomisation to the date of death from any cause. The ITT population was defined as all randomised subjects grouped according to their randomised treatment arm regardless of what treatments were actually received. Reported is the percentage of subjects with event.
    End point type
    Secondary
    End point timeframe
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    699
    702
    Units: percentage of subjects with event
        number (not applicable)
    9
    7.1
    No statistical analyses for this end point

    Secondary: Overall Survival (Follicular Lymphoma Population)

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    End point title
    		 Overall Survival (Follicular Lymphoma Population)
    End point description
    Overall survival in the follicular lymphoma population was defined as the time from the date of randomisation to the date of death from any cause. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received. Reported is the percentage of subjects with event.
    End point type
    Secondary
    End point timeframe
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: percentage of subjects with event
        number (not applicable)
    7.7
    5.8
    No statistical analyses for this end point

    Secondary: Event-Free Survival (Overall Study Population)

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    End point title
    		 Event-Free Survival (Overall Study Population)
    End point description
    Event-free survival was defined as the time from the date of randomisation to the date to disease progression/relapse, death from any cause, or initiation of a new anti-lymphoma treatment (NALT) on the basis of investigator assessment assessments with the use of Revised Response Criteria for Malignant Lymphoma. Disease progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumour measurements were obtained by CT/MRI. The ITT population was defined as all randomised subjects grouped according to their randomised treatment arm regardless of what treatments were actually received. Reported: percentage of subjects with event.
    End point type
    Secondary
    End point timeframe
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    699
    702
    Units: percentage of subjects with event
        number (not applicable)
    27
    19.7
    No statistical analyses for this end point

    Secondary: Event-Free Survival (Follicular Lymphoma Population)

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    End point title
    		 Event-Free Survival (Follicular Lymphoma Population)
    End point description
    Event-free survival: time from the date of randomisation to the date to disease progression/relapse, death from any cause, or initiation of a new anti-lymphoma treatment (NALT) on the basis of investigator assessment assessments with the use of Revised Response Criteria for Malignant Lymphoma. Disease progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumour measurements were obtained by CT/MRI. FL ITT population: all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received. Reported: percentage of subjects with event
    End point type
    Secondary
    End point timeframe
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: percentage of subjects with event
        number (not applicable)
    26.5
    18.6
    No statistical analyses for this end point

    Secondary: Disease-Free Survival (DFS) (Overall Study Population)

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    End point title
    		 Disease-Free Survival (DFS) (Overall Study Population)
    End point description
    DFS: time from the date of the first occurrence of a documented CR to the date of disease progression/ relapse, or death from any cause on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumour assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Subjects with CR within the ITT population were included in the analysis. Reported: percentage of subjects with event.
    End point type
    Secondary
    End point timeframe
    From first occurrence of documented CR to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    320
    343
    Units: percentage of subjects with event
        number (not applicable)
    12.8
    8.7
    No statistical analyses for this end point

    Secondary: Disease-Free Survival (DFS), (Follicular Lymphoma Population)

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    End point title
    		 Disease-Free Survival (DFS), (Follicular Lymphoma Population)
    End point description
    DFS: time from the date of the first occurrence of a documented CR to the date of disease progression/ relapse, or death from any cause on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumour assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Subjects with CR within the FL ITT population were included in the analysis. Reported: percentage of subjects with event.
    End point type
    Secondary
    End point timeframe
    From first occurrence of documented CR to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    281
    298
    Units: percentage of subjects with event
        number (not applicable)
    11.7
    9.1
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) (Overall Study Population), Investigator-Assessed

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    End point title
    		 Duration of Response (DOR) (Overall Study Population), Investigator-Assessed
    End point description
    DOR was defined as the time from first occurrence of a documented CR or PR to disease progression/relapse, or death from any cause. Tumour assessments by CT/MRI. CR: disappearance of all target lesions. PR: >/=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Subjects with CR or PR within the ITT population were included in the analysis. Reported is the percentage of subjects with event.
    End point type
    Secondary
    End point timeframe
    From first occurrence of documented CR or PR to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    656
    659
    Units: percentage of subjects with event
        number (not applicable)
    22.1
    15.6
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) (Follicular Lymphoma Population), Investigator-Assessed

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    End point title
    		 Duration of Response (DOR) (Follicular Lymphoma Population), Investigator-Assessed
    End point description
    DOR was defined as the time from first occurrence of a documented CR or PR to disease progression/relapse, or death from any cause. Tumour assessments by CT/MRI. CR: disappearance of all target lesions. PR: >/=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions, no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm.Subjects with CR or PR within the FL ITT population were included in the analysis. Reported is the percentage of subjects with event.
    End point type
    Secondary
    End point timeframe
    From first occurrence of documented CR or PR to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    567
    571
    Units: percentage of subjects with event
        number (not applicable)
    21.9
    15.4
    No statistical analyses for this end point

    Secondary: Time to Next Anti-Lymphoma Treatment (Overall Study Population)

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    End point title
    		 Time to Next Anti-Lymphoma Treatment (Overall Study Population)
    End point description
    Time to next anti-lymphoma treatment was defined as the time from the date of randomisation to the start date of the next anti-lymphoma treatment or death from any cause. Reported is the percentage of subjects who started next anti-lymphoma treatment. The ITT population was defined as all randomised subjects grouped according to their randomised treatment arm regardless of what treatments were actually received. Reported is the percentage of subjects with event.
    End point type
    Secondary
    End point timeframe
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    699
    702
    Units: percentage of subjects with event
        number (not applicable)
    19.7
    14.7
    No statistical analyses for this end point

    Secondary: Time to Next Anti-Lymphoma Treatment (Follicular Lymphoma Population)

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    End point title
    		 Time to Next Anti-Lymphoma Treatment (Follicular Lymphoma Population)
    End point description
    Time to next anti-lymphoma treatment was defined as the time from the date of randomisation to the start date of the next anti-lymphoma treatment or death from any cause. Reported is the percentage of subjects who started next anti-lymphoma treatment. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received. Reported is the percentage of subjects with event.
    End point type
    Secondary
    End point timeframe
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: percentage of subjects with event
        number (not applicable)
    18.5
    13.3
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Adverse Events

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    End point title
    		 Percentage of Subjects With Adverse Events
    End point description
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. The safety analysis population included all subjects who received any amount of any study drug and subjects were analysed according to the treatment received.
    End point type
    Secondary
    End point timeframe
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    692
    698
    Units: percentage of subjects
        number (not applicable)
    98.6
    99.6
    No statistical analyses for this end point

    Secondary: Change from Baseline in All Domains of FACT-G (Follicular Lymphoma Population)

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    End point title
    		 Change from Baseline in All Domains of FACT-G (Follicular Lymphoma Population)
    End point description
    FACT-G consists of the following 4 FACT-Lym sub-questionnaires: Physical Well-being (range: 0-28), Social/Family Well-being (range: 0-28), Emotional Well-being (range: 0-24) and Functional Well-being (range: 0-28). Higher scores indicate better outcomes. A positive change from baseline indicates improvement. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline (Induction Cycle 1, Day 1), end of study (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: Unitless score
    arithmetic mean (standard deviation)
        Physical Well-being (PW), Baseline (n=557, n=566)
    23.36 ± 4.77
    23.14 ± 4.85
        PW Change, Cycle 3, Day 1 (n=511,496)
    -0.91 ± 4.54
    -0.21 ± 4.59
        PW Change, End Induction (n=482, 480)
    -0.06 ± 4.83
    0.56 ± 5.14
        PW Change, Maint Month 2 (n=362, 398)
    0.83 ± 4.76
    1.42 ± 5.09
        PW Change, Maint Month 12 (n=362, 406)
    1.14 ± 4.29
    1.34 ± 4.74
        PW Change, End Maint (n=352, 370)
    0.86 ± 4.61
    1.27 ± 5.01
        Social/Family Well-being , Baseline (n=555, 563)
    22.84 ± 4.92
    23.28 ± 4.77
        S/FW Change, Cycle 3 Day 1 (n=506, 492)
    -0.52 ± 4.03
    -0.67 ± 3.92
        S/FW Change, End Induction (n=482, 475)
    -0.46 ± 4.77
    -0.56 ± 5
        S/FW Change, Maint Month 2 (n=359, 396)
    -0.39 ± 4.72
    -0.67 ± 4.68
        S/FW Change, Maint Month 12 (n=359, 403)
    -0.61 ± 5.56
    -0.97 ± 5.34
        S/FW Change, End Maint (n=352, 369)
    -0.98 ± 5.64
    -0.64 ± 5.18
        Emotional Well-being (EW), Baseline (n=556, 563)
    17.64 ± 4.19
    17.87 ± 4.13
        EW Change, Cycle 3 Day 1 (n=503, 490)
    1.49 ± 3.4
    1.35 ± 3.35
        EW Change, End Induction (n=478, 476)
    1.16 ± 3.9
    1.14 ± 3.87
        EW Change, Maint Month 2 (n=359, 396)
    1.77 ± 3.88
    1.49 ± 4.16
        EW Change, Maint Month 12 (n=360, 402)
    1.45 ± 3.92
    1.46 ± 3.88
        EW Change, End Maint (n=347, 368)
    1.37 ± 3.94
    1.49 ± 4.01
        Functional Well-being (FW), Baseline (n=556, 563)
    18.66 ± 6.19
    18.76 ± 5.98
        FW Change, Cycle 3 Day 1 (n=504, 488)
    -0.3 ± 5.3
    -0.07 ± 5.24
        FW Change, End Induction (n=480, 476)
    0.44 ± 5.63
    0.93 ± 5.85
        FW Change, Maint Month 2 (n=359, 396)
    1.04 ± 5.31
    1.25 ± 6.02
        FW Change, Maint Month 12 (n=360, 402)
    1.84 ± 5.54
    1.65 ± 5.95
        FW Change, End Maint (n=348, 369)
    1.37 ± 6.18
    1.79 ± 6.24
    No statistical analyses for this end point

    Secondary: Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population)

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    End point title
    		 Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population)
    End point description
    The FACT-Lym TOI Score for the follicular lymphoma population was derived from the following 3 individual FACT-Lym questionnaire subscale scores: Physical Well-being (range: 0-28), Functional Well-being (range: 0-28) and Lymphoma (range: 0-60). The FACT-Lym TOI Score is the sum of the 3 individual subscales (range 0-116). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline (Induction Cycle 1, Day 1), end of study (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: Unitless score
    arithmetic mean (standard deviation)
        TOI Score, Baseline (n=559, 567)
    86.61 ± 18.16
    86.94 ± 18.05
        TOI Score Change, Cycle 3 Day 1 (n=514, 497)
    0.46 ± 15.03
    2.18 ± 15.95
        TOI Score Change, End Induction (n=485, 481)
    2.91 ± 17
    4.57 ± 16.71
        TOI Score Change, Maint Month 2 (n=363, 400)
    6.22 ± 16.16
    7.17 ± 16.57
        TOI Score Change, Maint Month 12 (n=362, 408)
    7.61 ± 15.62
    7.2 ± 16.75
        TOI Score Change, End Maint (n=353, 373)
    6.52 ± 17.01
    7.57 ± 17.28
    No statistical analyses for this end point

    Secondary: Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population)

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    End point title
    		 Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population)
    End point description
    The FACT-Lym Individual Subscale Lymphoma Score for the follicular lymphoma population was derived from the Lymphoma subscale questionnaire (range: 0-60). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline (Induction Cycle 1, Day 1), end of study (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: Unitless score
    arithmetic mean (standard deviation)
        Lymphoma, Baseline (n=556, 563)
    45.01 ± 9.37
    45.54 ± 9.29
        Lymphoma Change, Cycle 3 Day 1 (n=509, 491)
    2.04 ± 7.18
    2.71 ± 7.46
        Lymphoma Change, End Induction (n=477, 478)
    2.99 ± 8.63
    3.01 ± 8.36
        Lymphoma Change, Maint Month 2 (n=360, 395)
    4.8 ± 8.29
    4.52 ± 8.32
        Lymphoma Change, Maint Month 12 (n=360, 404)
    4.93 ± 8.34
    4.27 ± 8.31
        Lymphoma Change, End Maint (n=350, 371)
    4.45 ± 8.83
    4.72 ± 8.73
    No statistical analyses for this end point

    Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population)

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    End point title
    		 Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population)
    End point description
    The FACT-Lym Total Score for the follicular lymphoma population was derived from the following 5 individual FACT-Lym questionnaire subscale scores: Physical Well-being (range: 0-28), Social/Family Well-being (range: 0-28), Emotional Well-being (range: 0-24),Functional Well-being (range: 0-28) and Lymphoma (range: 0-60). The FACT-Lym Total Score is the sum of all 5 individual subscales (range 0-168). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Baseline (Induction Cycle 1, Day 1), end of study (up to approximately 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: Unitless score
    arithmetic mean (standard deviation)
        Total Score, Baseline (n=552, 559)
    127.4 ± 22.43
    128.42 ± 22.16
        Total Score Change, Cycle 3 Day 1 (n=499, 484)
    1.98 ± 17.01
    3.21 ± 17.12
        Total Score Change, End Induction (n=471, 471)
    4.18 ± 19.75
    5.1 ± 20.03
        Total Score Change, Maint Month 2 (n=356, 392)
    8.4 ± 19.16
    8.13 ± 19.8
        Total Score Change, Maint Month 12 (n=358, 396)
    8.87 ± 19.31
    7.9 ± 19.55
        Total Score Change, End Maint (n=344, 366)
    7.48 ± 19.63
    8.83 ± 20.84
    No statistical analyses for this end point

    Secondary: Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase

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    End point title
    		 Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase
    End point description
    The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from ……to……… Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received. 9999=NE=Not estimable based on 0 or 1 subject evaluated.
    End point type
    Secondary
    End point timeframe
    Induction: Cycle 1 Day 1 (Baseline), Cycle 3 Day 1, End of Induction (up to 7 months) (1 Cycle=21 or 28 days); Maintenance: 2, 12, 25 months after Day 1 of last induction cycle (Cycle 6 or 8), Follow-up; up to data cut-off (up to 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: Unitless score
    arithmetic mean (standard deviation)
        Baseline Induction (n=558, 559)
    0.8 ± 0.24
    0.81 ± 0.21
        Change Baseline, Cycle 1 Day 1 (n=0, 0)
    9999 ± 9999
    9999 ± 9999
        Change Baseline, Cycle 3 Day 1 (n=505, 487)
    0.03 ± 0.21
    0.03 ± 0.2
        Change Baseline, Induction Completion (n=468, 466)
    0.04 ± 0.23
    0.03 ± 0.22
        Change Baseline, Maint/Obs Month 2 (n=348, 377)
    0.05 ± 0.23
    0.06 ± 0.22
        Change Baseline, Maint/Obs Month 12 (n=2, 1)
    0 ± 0
    -0.2 ± 9999
        Change Baseline, Maint/Obs Completion (n=0, 1)
    9999 ± 9999
    -0.1 ± 9999
    No statistical analyses for this end point

    Secondary: Change From Baseline in EQ-5D Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase

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    End point title
    		 Change From Baseline in EQ-5D Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase
    End point description
    The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from ……to……… Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received. 9999=NE=Not estimable based on 0 subjects evaluated.
    End point type
    Secondary
    End point timeframe
    Induction: Cycle 1 Day 1 (Baseline), Cycle 3 Day 1, End of Induction (up to 7 months) (1 Cycle=21 or 28 days); Maintenance: 2, 12, 25 months after Day 1 of last induction cycle (Cycle 6 or 8), Follow-up; up to data cut-off (up to 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: Unitless score
    arithmetic mean (standard deviation)
        Change Baseline, Maint/Obs Month 2 (n=11, 14)
    0.04 ± 0.34
    0.04 ± 0.14
        Change Baseline, Maint/Obs Month 12 (n=354, 395)
    0.06 ± 0.24
    0.06 ± 0.21
        Change Baseline, Maint/Obs Completion (n=344, 355)
    0.04 ± 0.24
    0.05 ± 0.23
    No statistical analyses for this end point

    Secondary: Change From Baseline in EQ-5D Questionnaire Summary Score (Follicular Lymphoma Population) During Follow Up Phase

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    End point title
    		 Change From Baseline in EQ-5D Questionnaire Summary Score (Follicular Lymphoma Population) During Follow Up Phase
    End point description
    The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from ……to……… Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. The FL ITT population was defined as all randomised subjects with follicular histology grouped according to their randomised treatment arm regardless of what treatments were actually received.
    End point type
    Secondary
    End point timeframe
    Induction: Cycle 1 Day 1 (Baseline), Cycle 3 Day 1, End of Induction (up to 7 months) (1 Cycle=21 or 28 days); Maintenance: 2, 12, 25 months after Day 1 of last induction cycle (Cycle 6 or 8), Follow-up; up to data cut-off (up to 4 years and 7 months)
    End point values
    		 Rituximab+Chemotherapy Obinutuzumab+Chemotherapy
    Number of subjects analysed
    601
    601
    Units: Unitless score
    arithmetic mean (standard deviation)
        Change Baseline, Follow-up Month 36 (n=149, 151)
    0.04 ± 0.23
    0.05 ± 0.25
        Change Baseline, Follow-up Month 48 (n=26, 29)
    0.07 ± 0.27
    0.08 ± 0.26
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to data cut-off (up to approximately 4 years and 7 months)
    Adverse event reporting additional description
    The safety analysis population included all subjects who received any amount of any study drug and subjects were analysed according to the treatment received.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Obinutuzumab+Chemotherapy
    Reporting group description
    		 Subjects received either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, subjects were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual subject during induction was chosen by the site prior to initiation of the study.

    Reporting group title
    Rituximab+Chemotherapy
    Reporting group description
    		 Subjects received either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period was followed by either a maintenance or observation period for responders or non-responders, respectively. Responders received rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders received no protocol specified treatment during the 2-year observation period. Finally, subjects were followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual subject during induction phase was chosen by the site prior to initiation of the study.

    Serious adverse events
    		 Obinutuzumab+Chemotherapy Rituximab+Chemotherapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    340 / 698 (48.71%)
    286 / 692 (41.33%)
         number of deaths (all causes)
    50
    63
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acoustic neuroma
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute lymphocytic leukaemia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Acute myeloid leukaemia
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Adenocarcinoma
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenoma benign
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    5 / 698 (0.72%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign neoplasm
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    4 / 698 (0.57%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cancer pain
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 698 (0.14%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Colorectal cancer
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ductal adenocarcinoma of pancreas
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Gastric cancer
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatic neoplasm
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hodgkin's disease
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hodgkin's disease nodular sclerosis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intraocular melanoma
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Keratoacanthoma
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malignant melanoma
         subjects affected / exposed
    1 / 698 (0.14%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Meningioma
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Neuroendocrine carcinoma of the skin
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Non-small cell lung cancer
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Non-small cell lung cancer stage IV
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Oestrogen receptor positive breast cancer
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    3 / 698 (0.43%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Schwannoma
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    4 / 698 (0.57%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    2 / 698 (0.29%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour flare
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulvovaginal warts
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Axillary vein thrombosis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Circulatory collapse
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 698 (0.14%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 698 (0.00%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    2 / 698 (0.29%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    7 / 698 (1.00%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    5 / 7
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Cancer surgery
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileectomy
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroidectomy
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    2 / 698 (0.29%)
    4 / 692 (0.58%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    4 / 698 (0.57%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    4 / 4
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cyst rupture
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 698 (0.14%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 2
    Device breakage
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    3 / 698 (0.43%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Hyperthermia
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ill-defined disorder
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Influenza like illness
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injection site extravasation
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    0 / 698 (0.00%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 698 (0.00%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    37 / 698 (5.30%)
    24 / 692 (3.47%)
         occurrences causally related to treatment / all
    23 / 42
    12 / 25
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stent-graft endoleak
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Allergy to anthropod bite
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic reaction
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytokine release syndrome
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypogammaglobulinaemia
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    0 / 698 (0.00%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian mass
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    1 / 698 (0.14%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal ulceration
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vulvovaginal pain
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute lung injury
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    2 / 698 (0.29%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 698 (0.14%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Cough
         subjects affected / exposed
    0 / 698 (0.00%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    10 / 698 (1.43%)
    8 / 692 (1.16%)
         occurrences causally related to treatment / all
    7 / 12
    3 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    2 / 698 (0.29%)
    4 / 692 (0.58%)
         occurrences causally related to treatment / all
    2 / 2
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung consolidation
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paranasal cyst
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal inflammation
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal paraesthesia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    5 / 698 (0.72%)
    5 / 692 (0.72%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    1 / 698 (0.14%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Productive cough
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary arterial hypertension
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    8 / 698 (1.15%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    2 / 9
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    3 / 698 (0.43%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vocal cord thickening
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol problem
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    2 / 698 (0.29%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emotional disorder
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Substance-induced psychotic disorder
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eastern cooperative oncology group performance status worsened
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accident
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anastomotic stenosis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 698 (0.14%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cartilage injury
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Compression fracture
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    3 / 698 (0.43%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 698 (0.29%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    36 / 698 (5.16%)
    18 / 692 (2.60%)
         occurrences causally related to treatment / all
    42 / 42
    20 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Medication error
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax traumatic
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seroma
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 698 (0.14%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Peroneal muscular atrophy
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    4 / 698 (0.57%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arrhytmia
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    9 / 698 (1.29%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    1 / 11
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    2 / 698 (0.29%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    2 / 3
    3 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac-respiratory arrest
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    2 / 698 (0.29%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 698 (0.00%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Myocardial ischaemia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    5 / 698 (0.72%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    5 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    3 / 698 (0.43%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    3 / 698 (0.43%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brachial plexopathy
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar syndrome
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral disorder
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebral ischaemia
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dementia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 698 (0.14%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness postural
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Epilepsy
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotonia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lethargy
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Monoparesis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorder
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuralgia
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic intolerance
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic tremor
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Presyncope
         subjects affected / exposed
    0 / 698 (0.00%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    3 / 698 (0.43%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    1 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    4 / 698 (0.57%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VIIth nerve paralysis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 698 (0.72%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    6 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Bone marrow failure
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    34 / 698 (4.87%)
    24 / 692 (3.47%)
         occurrences causally related to treatment / all
    42 / 45
    29 / 32
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolysis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Histiocytosis haematophagic
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune thrombocytopenic purpura
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    3 / 698 (0.43%)
    5 / 692 (0.72%)
         occurrences causally related to treatment / all
    2 / 3
    5 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    25 / 698 (3.58%)
    30 / 692 (4.34%)
         occurrences causally related to treatment / all
    28 / 29
    38 / 41
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenomegaly
         subjects affected / exposed
    2 / 698 (0.29%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    5 / 698 (0.72%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    12 / 12
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deaffness
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear pain
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Corneal opacity
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    10 / 698 (1.43%)
    5 / 692 (0.72%)
         occurrences causally related to treatment / all
    1 / 11
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 698 (0.00%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 698 (0.14%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    3 / 698 (0.43%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    3 / 698 (0.43%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    11 / 698 (1.58%)
    7 / 692 (1.01%)
         occurrences causally related to treatment / all
    7 / 12
    3 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterovesical fistula
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis eosinophilic
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    3 / 698 (0.43%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal villi atrophy
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mikulicz's syndrome
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mouth ulceration
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    6 / 698 (0.86%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    5 / 6
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    5 / 698 (0.72%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Vomiting
         subjects affected / exposed
    6 / 698 (0.86%)
    9 / 692 (1.30%)
         occurrences causally related to treatment / all
    4 / 6
    10 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stenosis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    2 / 698 (0.29%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    4 / 698 (0.57%)
    6 / 692 (0.87%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gallbladder pain
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis contact
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis exfoliative
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    5 / 698 (0.72%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    3 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Swelling face
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    3 / 698 (0.43%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute prerenal failure
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 698 (0.14%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal infarct
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthropathy
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    2 / 698 (0.29%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myopathy
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteitis deformans
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    2 / 698 (0.29%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    0 / 698 (0.00%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Temporomandibular joint syndrome
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemarthrosis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess intestinal
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 698 (0.14%)
    4 / 692 (0.58%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis infective
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    1 / 698 (0.14%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial tracheitis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bk virus infection
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast abscess
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    7 / 698 (1.00%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    2 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Campylobacter infection
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Catheter site cellulitis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    3 / 698 (0.43%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    1 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic sinusitis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    2 / 698 (0.29%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis enteroviral
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal infection
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epiglottitis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia infection
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    7 / 698 (1.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 7
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis Escherichia coli
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    7 / 698 (1.00%)
    8 / 692 (1.16%)
         occurrences causally related to treatment / all
    4 / 7
    4 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster disseminated
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster infection neurological
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster oticus
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected cyst
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    6 / 698 (0.86%)
    8 / 692 (1.16%)
         occurrences causally related to treatment / all
    2 / 7
    2 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    4 / 698 (0.57%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Influenza
         subjects affected / exposed
    3 / 698 (0.43%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    12 / 698 (1.72%)
    7 / 692 (1.01%)
         occurrences causally related to treatment / all
    8 / 19
    2 / 7
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Lung infection
         subjects affected / exposed
    8 / 698 (1.15%)
    6 / 692 (0.87%)
         occurrences causally related to treatment / all
    4 / 12
    6 / 6
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    Mastoiditis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis enteroviral
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal infection
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroborreliosis
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic infection
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    5 / 698 (0.72%)
    5 / 692 (0.72%)
         occurrences causally related to treatment / all
    6 / 7
    7 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Oesophageal candidiasis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal infection
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian bacterial infection
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periodontitis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal abscess
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii infection
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    42 / 698 (6.02%)
    30 / 692 (4.34%)
         occurrences causally related to treatment / all
    18 / 45
    14 / 35
         deaths causally related to treatment / all
    1 / 5
    0 / 2
    Pneumonia bacterial
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    0 / 698 (0.00%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    5 / 698 (0.72%)
    4 / 692 (0.58%)
         occurrences causally related to treatment / all
    3 / 5
    8 / 10
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Rhinitis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    13 / 698 (1.86%)
    6 / 692 (0.87%)
         occurrences causally related to treatment / all
    8 / 17
    4 / 6
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 698 (0.00%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sinusitis
         subjects affected / exposed
    1 / 698 (0.14%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis bacterial
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis fungal
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 698 (0.00%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tubo-ovarian abscess
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 698 (0.86%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    2 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    9 / 698 (1.29%)
    6 / 692 (0.87%)
         occurrences causally related to treatment / all
    2 / 9
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    3 / 698 (0.43%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    3 / 4
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 698 (0.14%)
    3 / 692 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral myositis
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    3 / 698 (0.43%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    2 / 698 (0.29%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    2 / 698 (0.29%)
    2 / 692 (0.29%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hyperglycaemia
         subjects affected / exposed
    1 / 698 (0.14%)
    0 / 692 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 698 (0.14%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    4 / 698 (0.57%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    3 / 698 (0.43%)
    1 / 692 (0.14%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Obinutuzumab+Chemotherapy Rituximab+Chemotherapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    679 / 698 (97.28%)
    663 / 692 (95.81%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    46 / 698 (6.59%)
    39 / 692 (5.64%)
         occurrences all number
    56
    40
    Hypertension
         subjects affected / exposed
    53 / 698 (7.59%)
    45 / 692 (6.50%)
         occurrences all number
    74
    61
    Hypotension
         subjects affected / exposed
    40 / 698 (5.73%)
    23 / 692 (3.32%)
         occurrences all number
    44
    26
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    32 / 698 (4.58%)
    36 / 692 (5.20%)
         occurrences all number
    38
    45
    Chest discomfort
         subjects affected / exposed
    42 / 698 (6.02%)
    37 / 692 (5.35%)
         occurrences all number
    44
    43
    Chills
         subjects affected / exposed
    120 / 698 (17.19%)
    71 / 692 (10.26%)
         occurrences all number
    162
    91
    Fatigue
         subjects affected / exposed
    259 / 698 (37.11%)
    247 / 692 (35.69%)
         occurrences all number
    374
    343
    Mucosal inflammation
         subjects affected / exposed
    30 / 698 (4.30%)
    40 / 692 (5.78%)
         occurrences all number
    35
    51
    Oedema peripheral
         subjects affected / exposed
    39 / 698 (5.59%)
    33 / 692 (4.77%)
         occurrences all number
    41
    40
    Pyrexia
         subjects affected / exposed
    187 / 698 (26.79%)
    141 / 692 (20.38%)
         occurrences all number
    245
    209
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    194 / 698 (27.79%)
    163 / 692 (23.55%)
         occurrences all number
    264
    214
    Dyspnoea
         subjects affected / exposed
    106 / 698 (15.19%)
    84 / 692 (12.14%)
         occurrences all number
    122
    97
    Oropharyngeal pain
         subjects affected / exposed
    76 / 698 (10.89%)
    69 / 692 (9.97%)
         occurrences all number
    91
    82
    Productive cough
         subjects affected / exposed
    35 / 698 (5.01%)
    27 / 692 (3.90%)
         occurrences all number
    41
    32
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    36 / 698 (5.16%)
    27 / 692 (3.90%)
         occurrences all number
    38
    29
    Insomnia
         subjects affected / exposed
    104 / 698 (14.90%)
    78 / 692 (11.27%)
         occurrences all number
    123
    88
    Investigations
    Weight decreased
         subjects affected / exposed
    33 / 698 (4.73%)
    38 / 692 (5.49%)
         occurrences all number
    35
    41
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    405 / 698 (58.02%)
    333 / 692 (48.12%)
         occurrences all number
    681
    534
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    66 / 698 (9.46%)
    49 / 692 (7.08%)
         occurrences all number
    73
    59
    Dysgeusia
         subjects affected / exposed
    60 / 698 (8.60%)
    55 / 692 (7.95%)
         occurrences all number
    72
    60
    Headache
         subjects affected / exposed
    138 / 698 (19.77%)
    114 / 692 (16.47%)
         occurrences all number
    208
    174
    Neuropathy peripheral
         subjects affected / exposed
    49 / 698 (7.02%)
    48 / 692 (6.94%)
         occurrences all number
    59
    49
    Paraesthesia
         subjects affected / exposed
    56 / 698 (8.02%)
    45 / 692 (6.50%)
         occurrences all number
    64
    60
    Peripheral sensory neuropathy
         subjects affected / exposed
    55 / 698 (7.88%)
    47 / 692 (6.79%)
         occurrences all number
    63
    50
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    65 / 698 (9.31%)
    65 / 692 (9.39%)
         occurrences all number
    77
    84
    Leukopenia
         subjects affected / exposed
    81 / 698 (11.60%)
    80 / 692 (11.56%)
         occurrences all number
    193
    234
    Neutropenia
         subjects affected / exposed
    328 / 698 (46.99%)
    285 / 692 (41.18%)
         occurrences all number
    801
    698
    Thrombocytopenia
         subjects affected / exposed
    84 / 698 (12.03%)
    48 / 692 (6.94%)
         occurrences all number
    147
    71
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    68 / 698 (9.74%)
    68 / 692 (9.83%)
         occurrences all number
    84
    83
    Abdominal pain upper
         subjects affected / exposed
    52 / 698 (7.45%)
    41 / 692 (5.92%)
         occurrences all number
    58
    45
    Constipation
         subjects affected / exposed
    239 / 698 (34.24%)
    205 / 692 (29.62%)
         occurrences all number
    307
    283
    Diarrhoea
         subjects affected / exposed
    183 / 698 (26.22%)
    150 / 692 (21.68%)
         occurrences all number
    275
    220
    Dyspepsia
         subjects affected / exposed
    59 / 698 (8.45%)
    42 / 692 (6.07%)
         occurrences all number
    74
    47
    Nausea
         subjects affected / exposed
    330 / 698 (47.28%)
    312 / 692 (45.09%)
         occurrences all number
    555
    534
    Stomatitis
         subjects affected / exposed
    53 / 698 (7.59%)
    50 / 692 (7.23%)
         occurrences all number
    71
    66
    Vomiting
         subjects affected / exposed
    160 / 698 (22.92%)
    134 / 692 (19.36%)
         occurrences all number
    208
    191
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    88 / 698 (12.61%)
    75 / 692 (10.84%)
         occurrences all number
    92
    76
    Dry skin
         subjects affected / exposed
    38 / 698 (5.44%)
    33 / 692 (4.77%)
         occurrences all number
    43
    36
    Erythema
         subjects affected / exposed
    37 / 698 (5.30%)
    32 / 692 (4.62%)
         occurrences all number
    40
    38
    Pruritus
         subjects affected / exposed
    91 / 698 (13.04%)
    89 / 692 (12.86%)
         occurrences all number
    109
    107
    Rash
         subjects affected / exposed
    113 / 698 (16.19%)
    120 / 692 (17.34%)
         occurrences all number
    142
    154
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    103 / 698 (14.76%)
    88 / 692 (12.72%)
         occurrences all number
    122
    110
    Back pain
         subjects affected / exposed
    94 / 698 (13.47%)
    108 / 692 (15.61%)
         occurrences all number
    117
    135
    Bone pain
         subjects affected / exposed
    36 / 698 (5.16%)
    37 / 692 (5.35%)
         occurrences all number
    41
    44
    Muscle spasms
         subjects affected / exposed
    37 / 698 (5.30%)
    36 / 692 (5.20%)
         occurrences all number
    42
    43
    Myalgia
         subjects affected / exposed
    47 / 698 (6.73%)
    30 / 692 (4.34%)
         occurrences all number
    54
    35
    Pain in extremity
         subjects affected / exposed
    63 / 698 (9.03%)
    56 / 692 (8.09%)
         occurrences all number
    71
    67
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    43 / 698 (6.16%)
    34 / 692 (4.91%)
         occurrences all number
    60
    44
    Herpes zoster
         subjects affected / exposed
    64 / 698 (9.17%)
    39 / 692 (5.64%)
         occurrences all number
    68
    44
    Lower respiratory tract infection
         subjects affected / exposed
    54 / 698 (7.74%)
    66 / 692 (9.54%)
         occurrences all number
    88
    91
    Nasopharyngitis
         subjects affected / exposed
    117 / 698 (16.76%)
    120 / 692 (17.34%)
         occurrences all number
    178
    183
    Oral herpes
         subjects affected / exposed
    39 / 698 (5.59%)
    36 / 692 (5.20%)
         occurrences all number
    46
    40
    Respiratory tract infection
         subjects affected / exposed
    35 / 698 (5.01%)
    31 / 692 (4.48%)
         occurrences all number
    55
    34
    Rhinitis
         subjects affected / exposed
    46 / 698 (6.59%)
    32 / 692 (4.62%)
         occurrences all number
    56
    41
    Sinusitis
         subjects affected / exposed
    67 / 698 (9.60%)
    42 / 692 (6.07%)
         occurrences all number
    90
    51
    Upper respiratory tract infection
         subjects affected / exposed
    125 / 698 (17.91%)
    119 / 692 (17.20%)
         occurrences all number
    175
    164
    Urinary tract infection
         subjects affected / exposed
    67 / 698 (9.60%)
    57 / 692 (8.24%)
         occurrences all number
    97
    84
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    87 / 698 (12.46%)
    77 / 692 (11.13%)
         occurrences all number
    102
    89
    Hypokalaemia
         subjects affected / exposed
    44 / 698 (6.30%)
    25 / 692 (3.61%)
         occurrences all number
    64
    37

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Jul 2011
    Allow for an early futility analysis of the first 170 randomized patients with follicular lymphoma based on the end-of-induction treatment complete response rates. The statistical methods sections were updated accordingly. Positron emission tomography (PET) was also made mandatory at screening and at end of induction therapy for the first 170 subjects with follicular lymphoma at all sites where PET scanners were available. The determination of minimal residual disease (MRD) based on polymerase chain reaction detection of BCL2/IgH-rearrangements within the malignant clone for all subjects with follicular lymphoma was also implemented.
    16 Jul 2012
    Implementation of a deoxyribonucleic acid (DNA) substudy in those subjects who give consent to the Roche Clinical Repository (RCR) and to DNA collection.
    28 May 2013
    Clarification of measuring and assessing the spleen and splenic response for marginal zone lymphoma (MZL) subjects.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    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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