Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   44338   clinical trials with a EudraCT protocol, of which   7368   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A PHASE 3 OPEN-LABEL RANDOMIZED STUDY TO COMPARE THE EFFICACY AND SAFETY OF RITUXIMAB PLUS LENALIDOMIDE (CC-5013) VERSUS RITUXIMAB PLUS CHEMOTHERAPY FOLLOWED BY RITUXIMAB IN SUBJECTS WITH PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA. The “RELEVANCE” trial

    Summary
    EudraCT number
    		 2011-002792-42
    Trial protocol
    		 BE   IT   DE   PT   ES  
    Global end of trial date
    30 Apr 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 May 2025
    First version publication date
    15 May 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RV-FOL-GELARC-0683C / RELEVANCE
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    LYSARC
    Sponsor organisation address
    CH Lyon Sud Bâtiment 2D, Pierre Bénite, France, 69945
    Public contact
    LYSARC, LYSARC, affaires-reglementaires@lysarc.org
    Scientific contact
    LYSARC, LYSARC, affaires-reglementaires@lysarc.org
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    31 Oct 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Apr 2024
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To compare the efficacy of rituximab plus lenalidomide to rituximab plus chemotherapy followed by rituximab in patients with previously untreated follicular lymphoma.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Dec 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 581
    Country: Number of subjects enrolled
    Belgium: 65
    Country: Number of subjects enrolled
    Spain: 58
    Country: Number of subjects enrolled
    Portugal: 13
    Country: Number of subjects enrolled
    Italy: 5
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Canada: 46
    Country: Number of subjects enrolled
    United States: 221
    Country: Number of subjects enrolled
    Japan: 34
    Country: Number of subjects enrolled
    Australia: 3
    Worldwide total number of subjects
    1030
    EEA total number of subjects
    726
    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)
    701
    From 65 to 84 years
    327
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 1030 participants were randomized, 1010 were treated

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Rituximab-Lenalidomide
    Arm description
    		 Rituximab, 375 mg/m^2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles. Six cycles of lenalidomide 20 mg daily on days 2-22 every 28 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    375 mg/m^2 on days 1, 8, 15, and 22 of cycle 1; then 375 mg/m^2 on day 1 of cycles 2-6; then responders only: 375mg/m^2 every 8 weeks for 12 cycles.

    Investigational medicinal product name
    Lenalidomide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    20 mg/day on days 2-22 for 6 cycles

    Arm title
    		 Investigator Choice
    Arm description
    		 Rituximab-CHOP: with six cycles of R-CHOP in 21 day cycles followed by two 21 day cycles of 375 mg/m^2 rituximab and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles, OR Rituximab-CVP: with eight cycles of R-CVP in 21 day cycles; and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles, OR Rituximab-Bendamustine: with rituximab 375 mg/m^2 (day 1) plus bendamustine 90 mg/m^2 (days 1 + 2) every 28 days for six cycles; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    375 mg/m^2 on days 1, 8, 15, and 22 of cycle 1; then 375 mg/m^2 on day 1 of cycles 2-6; then responders only: 375mg/m^2 every 8 weeks for 12 cycles.

    Investigational medicinal product name
    CHOP - Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Six cycles of R-CHOP in 21-day cycles: Vincristine, 1.4 mg/m2 (2 mg cap) IV on day 1

    Investigational medicinal product name
    CHOP - Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Six cycles of R-CHOP in 21-day cycles: Prednisone, 100 mg/day PO on days 1-5

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    90mg/m 2 on days 1 + 2 every 28 days for six cycles

    Investigational medicinal product name
    CVP- Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Eight cycles of R-CVP in 21-day cycles: Prednisone, 100 mg/day PO on days 1-5

    Investigational medicinal product name
    CVP - Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eight cycles of R-CVP in 21-day cycles Cyclophosphamide 750 mg/m 2 day 1

    Investigational medicinal product name
    CVP - Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eight cycles of R-CVP in 21 day cycles Vincristine 1.4 mg/m 2 (2mgcap) day 1,

    Investigational medicinal product name
    CHOP - Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Six cycles of R-CHOP in 21-day cycles: Doxorubicin,50mg/m2 IV on day 1

    Investigational medicinal product name
    CHOP - Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Six cycles of R-CHOP in 21-day cycles: Cyclophosphamide,750mg/m2 IV on day 1

    Number of subjects in period 1
    		Rituximab-Lenalidomide Investigator Choice
    Started
    513
    517
    Completed
    507
    503
    Not completed
    6
    14
         Other reasons
    6
    14
    Period 2
    Period 2 title
    Treatment
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Rituximab-Lenalidomide
    Arm description
    		 Rituximab, 375 mg/m^2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles. Six cycles of lenalidomide 20 mg daily on days 2-22 every 28 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    375 mg/m^2 on days 1, 8, 15, and 22 of cycle 1; then 375 mg/m^2 on day 1 of cycles 2-6; then responders only: 375mg/m^2 every 8 weeks for 12 cycles.

    Investigational medicinal product name
    Lenalidomide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    20 mg/day on days 2-22 for 6 cycles

    Arm title
    		 Investigator Choice
    Arm description
    		 Rituximab-CHOP: with six cycles of R-CHOP in 21 day cycles followed by two 21 day cycles of 375 mg/m^2 rituximab and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles, OR Rituximab-CVP: with eight cycles of R-CVP in 21 day cycles; and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles, OR Rituximab-Bendamustine: with rituximab 375 mg/m^2 (day 1) plus bendamustine 90 mg/m^2 (days 1 + 2) every 28 days for six cycles; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    375 mg/m^2 on days 1, 8, 15, and 22 of cycle 1; then 375 mg/m^2 on day 1 of cycles 2-6; then responders only: 375mg/m^2 every 8 weeks for 12 cycles.

    Investigational medicinal product name
    CHOP - Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Six cycles of R-CHOP in 21-day cycles: Doxorubicin,50mg/m2 IV on day 1

    Investigational medicinal product name
    CHOP - Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    Six cycles of R-CHOP in 21-day cycles: Vincristine, 1.4 mg/m2 (2 mg cap) IV on day 1

    Investigational medicinal product name
    CHOP - Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Six cycles of R-CHOP in 21-day cycles: Prednisone, 100 mg/day PO on days 1-5

    Investigational medicinal product name
    Bendamustine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    90mg/m 2 on days 1 + 2 every 28 days for six cycles

    Investigational medicinal product name
    CVP- Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Eight cycles of R-CVP in 21-day cycles: Prednisone, 100 mg/day PO on days 1-5

    Investigational medicinal product name
    CVP - Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eight cycles of R-CVP in 21-day cycles Cyclophosphamide 750 mg/m 2 day 1

    Investigational medicinal product name
    CVP - Vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eight cycles of R-CVP in 21 day cycles Vincristine 1.4 mg/m 2 (2mgcap) day 1,

    Investigational medicinal product name
    CHOP - Cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Six cycles of R-CHOP in 21-day cycles: Cyclophosphamide,750mg/m2 IV on day 1

    Number of subjects in period 2
    		Rituximab-Lenalidomide Investigator Choice
    Started
    507
    503
    Completed
    350
    357
    Not completed
    157
    146
         Adverse event, serious fatal
    -
    1
         Consent withdrawn by subject
    3
    14
         Toxicity
    44
    16
         Major protocol violation
    1
    6
         Voluntary treatment discontinuation
    8
    4
         Progression
    64
    71
         Concurrent illness
    12
    9
         Other reasons
    10
    22
         Insufficient response
    15
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Rituximab-Lenalidomide
    Reporting group description
    		 Rituximab, 375 mg/m^2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles. Six cycles of lenalidomide 20 mg daily on days 2-22 every 28 days.

    Reporting group title
    Investigator Choice
    Reporting group description
    		 Rituximab-CHOP: with six cycles of R-CHOP in 21 day cycles followed by two 21 day cycles of 375 mg/m^2 rituximab and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles, OR Rituximab-CVP: with eight cycles of R-CVP in 21 day cycles; and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles, OR Rituximab-Bendamustine: with rituximab 375 mg/m^2 (day 1) plus bendamustine 90 mg/m^2 (days 1 + 2) every 28 days for six cycles; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles.

    Reporting group values
    		 Rituximab-Lenalidomide Investigator Choice Total
    Number of subjects
    		 513 517 1030
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 348 353 701
        From 65-84 years
    		 163 164 327
        85 years and over
    		 2 0 2
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 58.5 ( 11.23 ) 58.3 ( 11.38 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 262 266 528
        Male
    		 251 251 502

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Rituximab-Lenalidomide
    Reporting group description
    		 Rituximab, 375 mg/m^2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles. Six cycles of lenalidomide 20 mg daily on days 2-22 every 28 days.

    Reporting group title
    Investigator Choice
    Reporting group description
    		 Rituximab-CHOP: with six cycles of R-CHOP in 21 day cycles followed by two 21 day cycles of 375 mg/m^2 rituximab and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles, OR Rituximab-CVP: with eight cycles of R-CVP in 21 day cycles; and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles, OR Rituximab-Bendamustine: with rituximab 375 mg/m^2 (day 1) plus bendamustine 90 mg/m^2 (days 1 + 2) every 28 days for six cycles; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles.
    Reporting group title
    Rituximab-Lenalidomide
    Reporting group description
    		 Rituximab, 375 mg/m^2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles. Six cycles of lenalidomide 20 mg daily on days 2-22 every 28 days.

    Reporting group title
    Investigator Choice
    Reporting group description
    		 Rituximab-CHOP: with six cycles of R-CHOP in 21 day cycles followed by two 21 day cycles of 375 mg/m^2 rituximab and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles, OR Rituximab-CVP: with eight cycles of R-CVP in 21 day cycles; and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles, OR Rituximab-Bendamustine: with rituximab 375 mg/m^2 (day 1) plus bendamustine 90 mg/m^2 (days 1 + 2) every 28 days for six cycles; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles.

    Primary: Complete Response Rate (CR/CRu) at 120 weeks by Independent Central Review

    		 Close Top of page
    End point title
    		 Complete Response Rate (CR/CRu) at 120 weeks by Independent Central Review
    End point description
    The Complete Response Rate (CR/CRu) is the percentage of participants who achieve complete response (CR/CRu) at 120 weeks as assessed per Independent Central Review. - Complete Response (CR): Disappearance of all evidence of disease. - Complete Response Unconfirmed (CRu): Disappearance of all disease with the exception of residual lymph nodes that are 1.5 cm or less in greatest transverse diameter and/or indeterminate bone marrow findings.
    End point type
    Primary
    End point timeframe
    At 120 weeks
    End point values
    		 Rituximab-Lenalidomide Investigator Choice
    Number of subjects analysed
    513
    517
    Units: Percent of participants
        number (confidence interval 95%)
    48.1 (43.7 to 52.6)
    53.0 (48.6 to 57.4)
    Statistical analysis title
    		 Complete Response Rate (CR/CRu) at 120 Weeks
    Comparison groups
    Rituximab-Lenalidomide v Investigator Choice
    Number of subjects included in analysis
    1030
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.128
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Primary: Progression-free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-free Survival (PFS)
    End point description
    Progression-free survival (PFS) is defined as the time from randomization into the study to the first observation of documented disease progression or death due to any cause. Progressive Disease (PD) is characterized by any of the following: -An increase of at least 50% in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal lymph node(s) or other disease sites. -The appearance of any new lesion during or after treatment. -An increase of at least 50% in the longest diameter of a previously identified node that was 1 cm or more in its short axis. -An increase of at least 50% in the size of other lesions (e.g., splenomegaly, hepatomegaly). Based on Kaplan-Meier estimates. Censoring rules based on EMA guidelines. "99999"=N/A
    End point type
    Primary
    End point timeframe
    From randomization into the study to the first observation of documented disease progression or death due to any cause (up to approximately 140 months).
    End point values
    		 Rituximab-Lenalidomide Investigator Choice
    Number of subjects analysed
    513
    517
    Units: Months
        median (confidence interval 95%)
    110.6 (85.5 to 122.1)
    102.8 (83.4 to 123.5)
    Statistical analysis title
    		 Progression-free Survival (PFS)
    Comparison groups
    Rituximab-Lenalidomide v Investigator Choice
    Number of subjects included in analysis
    1030
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.499
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.785
         upper limit
    		 1.125

    Secondary: Complete Response Rate (CR) at 120 weeks per Independent Central Review

    		 Close Top of page
    End point title
    		 Complete Response Rate (CR) at 120 weeks per Independent Central Review
    End point description
    The Complete Response Rate (CR) is the percentage of participants who achieve complete response (CR) at 120 weeks as assessed per Independent Central Review. - Complete Response (CR): Disappearance of all evidence of disease.
    End point type
    Secondary
    End point timeframe
    At 120 weeks
    End point values
    		 Rituximab-Lenalidomide Investigator Choice
    Number of subjects analysed
    513
    517
    Units: Percent of participants
        number (confidence interval 95%)
    27.7 (23.8 to 31.8)
    32.7 (28.7 to 36.9)
    No statistical analyses for this end point

    Secondary: Event-free Survival (EFS)

    		 Close Top of page
    End point title
    		 Event-free Survival (EFS)
    End point description
    Event Free Survival (EFS) is the time a participant remains free from certain negative events (disease progression, relapse, initiation of a new anti-lymphoma treatment, or death) between the date of randomization to the date of first documented progression, relapse, and initiation of a new anti-lymphoma treatment or death by any cause. Responding participants and those lost to follow up were censored at their last tumor assessment date. Progressive Disease (PD) is characterized by any of the following: -An increase of at least 50% in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal lymph node(s) or other disease sites. -The appearance of any new lesion during or after treatment. -An increase of at least 50% in the longest diameter of a previously identified node that was 1 cm or more in its short axis. -An increase of at least 50% in the size of other lesions (e.g., splenomegaly, hepatomegaly). Based on Kaplan-Meier estimates. "99999"=N/A
    End point type
    Secondary
    End point timeframe
    From randomization to the date of first documented progression, relapse, and initiation of a new anti-lymphoma treatment or death by any cause (up to approximately 140 months).
    End point values
    		 Rituximab-Lenalidomide Investigator Choice
    Number of subjects analysed
    513
    517
    Units: Months
        median (confidence interval 95%)
    130.6 (121.9 to 99999)
    132.3 (115.7 to 99999)
    Statistical analysis title
    		 Event Free Survival (EFS)
    Comparison groups
    Rituximab-Lenalidomide v Investigator Choice
    Number of subjects included in analysis
    1030
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.038
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.854
         upper limit
    		 1.261

    Secondary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    Overall survival (OS) is defined as the median length of time a participant stays alive from randomization. Participants who died, regardless of the cause of death, were considered to have had an event. Participants who withdrew consent for the study were considered censored at the time of withdrawal. Participants who completed the study and were still alive at the time of the clinical data cut-off date were censored. All participants who were lost to follow-up prior to the clinical data cut-off date were also considered censored at the time of last contact. Based on Kaplan-Meier estimates. "99999"=N/A
    End point type
    Secondary
    End point timeframe
    From randomization to the date of death by any cause (up to approximately 144 months).
    End point values
    		 Rituximab-Lenalidomide Investigator Choice
    Number of subjects analysed
    513
    517
    Units: Months
        median (confidence interval 95%)
    99999 (-99999 to 99999)
    99999 (-99999 to 99999)
    Statistical analysis title
    		 Overall survival (OS)
    Comparison groups
    Rituximab-Lenalidomide v Investigator Choice
    Number of subjects included in analysis
    1030
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.775
         upper limit
    		 1.395

    Secondary: Time to Next Anti-Lymphoma Treatment (TTNLT)

    		 Close Top of page
    End point title
    		 Time to Next Anti-Lymphoma Treatment (TTNLT)
    End point description
    Time to Next Lymphoma Treatment (TTNLT) was measured from the date of randomization to the date of the first documented administration of any new anti-lymphoma treatment (such as chemotherapy, radiotherapy, radio-immunotherapy, or immunotherapy). Participants who continued to respond to treatment or who were lost to follow-up were considered censored on their last visit date. Participants who died (due to any cause) before receiving a new anti-lymphoma treatment were included in the statistical analysis, with death being counted as an event. Based on Kaplan-Meier estimates. "99999"=N/A
    End point type
    Secondary
    End point timeframe
    From the date of randomization to the date of the first documented administration of any new anti-lymphoma treatment (up to approximately 140 months).
    End point values
    		 Rituximab-Lenalidomide Investigator Choice
    Number of subjects analysed
    513
    517
    Units: Months
        median (confidence interval 95%)
    99999 (-99999 to 99999)
    99999 (-99999 to 99999)
    Statistical analysis title
    		 Time to Next Anti-Lymphoma Treatment (TTNLT)
    Comparison groups
    Rituximab-Lenalidomide v Investigator Choice
    Number of subjects included in analysis
    1030
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.809
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.651
         upper limit
    		 1.006

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Death was assessed from first dose to study completion (up to approximately 144 months). SAEs and Other AEs were assessed from first dose to 28 days post the last dose (an average of 25 months and a maximum of 33 months).
    Adverse event reporting additional description
    The number at Risk for death, Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication. The data for the Investigator Choice chemotherapy arms, previously grouped together, presented separately for each specific chemotherapy treatment that participants received.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Investigator's Choice: Rituximab-CHOP
    Reporting group description
    		 Six cycles of R-CHOP in 21 day cycles followed by two 21 day cycles of 375 mg/m^2 rituximab and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles.

    Reporting group title
    Investigator's Choice: Rituximab-CVP
    Reporting group description
    		 Eight cycles of R-CVP in 21 day cycles; and 7 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles.

    Reporting group title
    Rituximab-Lenalidomide
    Reporting group description
    		 Rituximab, 375 mg/m^2 on days 1, 8, 15 and 22 of cycle 1, day 1 of cycles 2 to 6; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles. Six cycles of lenalidomide 20 mg daily on days 2-22 every 28 days.

    Reporting group title
    Investigator's Choice: Rituximab-Bendamustine
    Reporting group description
    		 Rituximab 375 mg/m^2 (day 1) plus bendamustine 90 mg/m^2 (days 1 + 2) every 28 days for six cycles; and 8 weeks later responding patients continue with 375 mg/m^2 rituximab every 8 weeks for 12 cycles.

    Serious adverse events
    		 Investigator's Choice: Rituximab-CHOP Investigator's Choice: Rituximab-CVP Rituximab-Lenalidomide Investigator's Choice: Rituximab-Bendamustine
    Total subjects affected by serious adverse events
         subjects affected / exposed
    109 / 365 (29.86%)
    7 / 26 (26.92%)
    181 / 507 (35.70%)
    32 / 112 (28.57%)
         number of deaths (all causes)
    69
    6
    87
    12
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ACUTE LYMPHOCYTIC LEUKAEMIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ADENOCARCINOMA OF COLON
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CLEAR CELL RENAL CELL CARCINOMA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BENIGN NEOPLASM OF EPIDIDYMIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BENIGN RENAL NEOPLASM
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BOWEN'S DISEASE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BREAST CANCER
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BASAL CELL CARCINOMA
         subjects affected / exposed
    5 / 365 (1.37%)
    0 / 26 (0.00%)
    4 / 507 (0.79%)
    4 / 112 (3.57%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 0
    0 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLON CANCER
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLORECTAL ADENOMA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENDOMETRIAL CANCER
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GALLBLADDER ADENOCARCINOMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INVASIVE DUCTAL BREAST CARCINOMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LYMPHOPROLIFERATIVE DISORDER
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LARYNGEAL SQUAMOUS CELL CARCINOMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG ADENOCARCINOMA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG NEOPLASM MALIGNANT
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG SQUAMOUS CELL CARCINOMA STAGE III
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    KERATOACANTHOMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MALIGNANT MELANOMA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MENINGIOMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MENINGIOMA BENIGN
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NON-SMALL CELL LUNG CANCER
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PAPILLARY THYROID CANCER
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA OF SKIN
         subjects affected / exposed
    1 / 365 (0.27%)
    1 / 26 (3.85%)
    4 / 507 (0.79%)
    6 / 112 (5.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    3 / 4
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RENAL CANCER
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SKIN CANCER
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SMALL CELL LUNG CANCER METASTATIC
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA OF LUNG
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RECTAL ADENOCARCINOMA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA OF THE CERVIX
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SQUAMOUS CELL CARCINOMA OF THE TONGUE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TUMOUR FLARE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    5 / 507 (0.99%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    5 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    UTERINE LEIOMYOMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    AORTIC ANEURYSM RUPTURE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    AORTIC DISSECTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ARTERIAL THROMBOSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ARTERIOVENOUS FISTULA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BLEEDING VARICOSE VEIN
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMATOMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ARTERITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ORTHOSTATIC HYPOTENSION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PHLEBITIS
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VASCULITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SUPERFICIAL VEIN THROMBOSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    THROMBOSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PHLEBITIS SUPERFICIAL
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    UMBILICAL HERNIA REPAIR
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    CHEST PAIN
         subjects affected / exposed
    2 / 365 (0.55%)
    1 / 26 (3.85%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ASTHENIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ADVERSE DRUG REACTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARDIAC DEATH
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    FATIGUE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FOREIGN BODY REACTION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    4 / 507 (0.79%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERTHERMIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MALAISE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 26 (3.85%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    13 / 507 (2.56%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    7 / 14
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    STRANGULATED HERNIA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FACE OEDEMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    ANAPHYLACTIC SHOCK
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ANAPHYLACTIC REACTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERSENSITIVITY
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DRUG HYPERSENSITIVITY
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ANAPHYLACTOID REACTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    CYSTOCELE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PENILE ADHESION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PROSTATITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 26 (3.85%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE PULMONARY OEDEMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ASTHMA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LARYNGEAL OEDEMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COUGH
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTERSTITIAL LUNG DISEASE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHOPNEUMOPATHY
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LUNG DISORDER
         subjects affected / exposed
    1 / 365 (0.27%)
    1 / 26 (3.85%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    9 / 507 (1.78%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    4 / 10
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    PLEURITIC PAIN
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 26 (3.85%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONITIS
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    5 / 507 (0.99%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    5 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    PULMONARY OEDEMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    CONVERSION DISORDER
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BIPOLAR DISORDER
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEPRESSION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MANIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    DEVICE BREAKAGE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    PORTAL VEIN THROMBOSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HEPATITIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHOLECYSTITIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHOLECYSTITIS ACUTE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BILIARY DILATATION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BILIARY OBSTRUCTION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHOLANGITIS ACUTE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHOLELITHIASIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    ELECTROCARDIOGRAM T WAVE INVERSION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TROPONIN INCREASED
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TROPONIN T INCREASED
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINE OUTPUT DECREASED
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    WEIGHT DECREASED
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FIBRIN D DIMER INCREASED
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    AORTIC INJURY
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ACCIDENTAL OVERDOSE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHEST INJURY
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FALL
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAND FRACTURE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HIP FRACTURE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HUMERUS FRACTURE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INCISIONAL HERNIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INFUSION RELATED REACTION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    9 / 507 (1.78%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    9 / 9
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LIGAMENT RUPTURE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MULTIPLE INJURIES
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    POSTOPERATIVE WOUND COMPLICATION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RADIUS FRACTURE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SPINAL COLUMN INJURY
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SPINAL COMPRESSION FRACTURE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SPINAL FRACTURE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ULNA FRACTURE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    GASTROINTESTINAL MALFORMATION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRUGADA SYNDROME
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    ACUTE MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ACUTE CORONARY SYNDROME
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARDIOMYOPATHY
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARDIAC FAILURE
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 26 (3.85%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARDIAC ARREST
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    BRADYCARDIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ATRIOVENTRICULAR BLOCK COMPLETE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ATRIAL FLUTTER
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    3 / 507 (0.59%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ARRHYTHMIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    AORTIC VALVE INCOMPETENCE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARDIORENAL SYNDROME
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ANGINA PECTORIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SINUS NODE DYSFUNCTION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERICARDIAL EFFUSION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PALPITATIONS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MYOCARDIAL ISCHAEMIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    CORONARY ARTERY STENOSIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARDIOTOXICITY
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    MIGRAINE WITH AURA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL INFARCTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    3 / 507 (0.59%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HEADACHE
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ISCHAEMIC STROKE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CARPAL TUNNEL SYNDROME
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OPTIC NEURITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SCIATICA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEIZURE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SPEECH DISORDER
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 26 (3.85%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SYNCOPE
         subjects affected / exposed
    1 / 365 (0.27%)
    1 / 26 (3.85%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    AGRANULOCYTOSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    EOSINOPHILIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FEBRILE BONE MARROW APLASIA
         subjects affected / exposed
    3 / 365 (0.82%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    17 / 365 (4.66%)
    1 / 26 (3.85%)
    9 / 507 (1.78%)
    6 / 112 (5.36%)
         occurrences causally related to treatment / all
    18 / 19
    1 / 1
    8 / 9
    6 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    3 / 365 (0.82%)
    0 / 26 (0.00%)
    3 / 507 (0.59%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PANCYTOPENIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    3 / 507 (0.59%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IRON DEFICIENCY ANAEMIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    VERTIGO
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    RETINAL DETACHMENT
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PAPILLOEDEMA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CATARACT
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ABDOMINAL PAIN
         subjects affected / exposed
    3 / 365 (0.82%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    3 / 365 (0.82%)
    0 / 26 (0.00%)
    4 / 507 (0.79%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    3 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ASCITES
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLITIS ISCHAEMIC
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CONSTIPATION
         subjects affected / exposed
    3 / 365 (0.82%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTRITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 26 (3.85%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FAECALOMA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENTEROCOLITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIVERTICULUM INTESTINAL
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL PAIN
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    3 / 365 (0.82%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 365 (0.27%)
    1 / 26 (3.85%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INGUINAL HERNIA
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HERNIAL EVENTRATION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS ACUTE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    POOR DENTAL CONDITION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SUBILEUS
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    CUTANEOUS VASCULITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CAPILLARITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ECZEMA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERSENSITIVITY VASCULITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEUTROPHILIC DERMATOSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 26 (3.85%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RASH
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    10 / 507 (1.97%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    5 / 10
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VASCULAR PURPURA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RASH PAPULAR
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    STEVENS-JOHNSON SYNDROME
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TOXIC SKIN ERUPTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    3 / 507 (0.59%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URTICARIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RASH MACULO-PAPULAR
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    2 / 365 (0.55%)
    1 / 26 (3.85%)
    3 / 507 (0.59%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CALCULUS URINARY
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CYSTITIS HAEMORRHAGIC
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY RETENTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYDRONEPHROSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEPHROLITHIASIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    POLLAKIURIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    5 / 507 (0.99%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    RENAL TUBULAR NECROSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMATURIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    HYPERTHYROIDISM
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BACK PAIN
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    3 / 507 (0.59%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BONE PAIN
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OSTEONECROSIS OF JAW
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FLANK PAIN
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTERVERTEBRAL DISC PROTRUSION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NECK PAIN
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OSTEOARTHRITIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHONDROCALCINOSIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SOFT TISSUE NECROSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SPINAL STENOSIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SPONDYLITIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    CELLULITIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CAMPYLOBACTER SEPSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BRONCHIOLITIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BACTERIURIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BACTERIAL SEPSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    APPENDICITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CLOSTRIDIUM DIFFICILE INFECTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ESCHERICHIA SEPSIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    ERYSIPELAS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ENTEROBACTER SEPSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEVICE RELATED SEPSIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ESCHERICHIA URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS VIRAL
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GANGRENE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FUSOBACTERIUM INFECTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GENITAL HERPES SIMPLEX
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    H1N1 INFLUENZA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OESOPHAGEAL CANDIDIASIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MENINGITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE INFECTION
         subjects affected / exposed
    1 / 365 (0.27%)
    1 / 26 (3.85%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    2 / 365 (0.55%)
    1 / 26 (3.85%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INFECTION
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HUMAN EHRLICHIOSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HERPES ZOSTER
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HERPES OPHTHALMIC
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HEPATITIS E
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PARONYCHIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA HAEMOPHILUS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA PNEUMOCOCCAL
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA STAPHYLOCOCCAL
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA STREPTOCOCCAL
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA VIRAL
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMOCYSTIS JIROVECII PNEUMONIA
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PILONIDAL DISEASE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PHARYNGITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERITONITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    6 / 365 (1.64%)
    0 / 26 (0.00%)
    11 / 507 (2.17%)
    3 / 112 (2.68%)
         occurrences causally related to treatment / all
    3 / 6
    0 / 0
    4 / 13
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PSEUDOMONAL SEPSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PSEUDOMONAS INFECTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TOOTH ABSCESS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TONSILLITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SOFT TISSUE INFECTION
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 26 (3.85%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SINUSITIS
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 26 (3.85%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    2 / 365 (0.55%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYELONEPHRITIS ACUTE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYELONEPHRITIS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    WOUND INFECTION STAPHYLOCOCCAL
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    WOUND INFECTION BACTERIAL
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    UROSEPSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 26 (3.85%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION ENTEROCOCCAL
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    5 / 507 (0.99%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VIRAL INFECTION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEHYDRATION
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIABETES MELLITUS
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIABETES MELLITUS INADEQUATE CONTROL
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIABETIC KETOACIDOSIS
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERGLYCAEMIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERKALAEMIA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    0 / 507 (0.00%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOALBUMINAEMIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOKALAEMIA
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERCALCAEMIA
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MALNUTRITION
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    1 / 507 (0.20%)
    0 / 112 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TUMOUR LYSIS SYNDROME
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 26 (0.00%)
    3 / 507 (0.59%)
    1 / 112 (0.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Investigator's Choice: Rituximab-CHOP Investigator's Choice: Rituximab-CVP Rituximab-Lenalidomide Investigator's Choice: Rituximab-Bendamustine
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    351 / 365 (96.16%)
    26 / 26 (100.00%)
    496 / 507 (97.83%)
    108 / 112 (96.43%)
    Vascular disorders
    HOT FLUSH
         subjects affected / exposed
    5 / 365 (1.37%)
    0 / 26 (0.00%)
    16 / 507 (3.16%)
    6 / 112 (5.36%)
         occurrences all number
    5
    0
    17
    6
    PHLEBITIS
         subjects affected / exposed
    4 / 365 (1.10%)
    0 / 26 (0.00%)
    2 / 507 (0.39%)
    6 / 112 (5.36%)
         occurrences all number
    4
    0
    2
    6
    HYPOTENSION
         subjects affected / exposed
    5 / 365 (1.37%)
    2 / 26 (7.69%)
    16 / 507 (3.16%)
    1 / 112 (0.89%)
         occurrences all number
    6
    2
    18
    1
    HYPERTENSION
         subjects affected / exposed
    13 / 365 (3.56%)
    2 / 26 (7.69%)
    23 / 507 (4.54%)
    9 / 112 (8.04%)
         occurrences all number
    15
    2
    27
    9
    General disorders and administration site conditions
    PYREXIA
         subjects affected / exposed
    43 / 365 (11.78%)
    4 / 26 (15.38%)
    90 / 507 (17.75%)
    23 / 112 (20.54%)
         occurrences all number
    52
    5
    110
    28
    PAIN
         subjects affected / exposed
    9 / 365 (2.47%)
    2 / 26 (7.69%)
    9 / 507 (1.78%)
    4 / 112 (3.57%)
         occurrences all number
    10
    2
    10
    4
    OEDEMA PERIPHERAL
         subjects affected / exposed
    31 / 365 (8.49%)
    4 / 26 (15.38%)
    68 / 507 (13.41%)
    12 / 112 (10.71%)
         occurrences all number
    33
    4
    84
    17
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    19 / 365 (5.21%)
    0 / 26 (0.00%)
    15 / 507 (2.96%)
    2 / 112 (1.79%)
         occurrences all number
    25
    0
    23
    3
    MALAISE
         subjects affected / exposed
    8 / 365 (2.19%)
    0 / 26 (0.00%)
    11 / 507 (2.17%)
    6 / 112 (5.36%)
         occurrences all number
    8
    0
    12
    6
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    5 / 365 (1.37%)
    0 / 26 (0.00%)
    18 / 507 (3.55%)
    7 / 112 (6.25%)
         occurrences all number
    7
    0
    19
    8
    FATIGUE
         subjects affected / exposed
    67 / 365 (18.36%)
    6 / 26 (23.08%)
    116 / 507 (22.88%)
    73 / 112 (65.18%)
         occurrences all number
    80
    7
    155
    111
    CHILLS
         subjects affected / exposed
    2 / 365 (0.55%)
    1 / 26 (3.85%)
    20 / 507 (3.94%)
    11 / 112 (9.82%)
         occurrences all number
    4
    1
    22
    12
    ASTHENIA
         subjects affected / exposed
    129 / 365 (35.34%)
    6 / 26 (23.08%)
    144 / 507 (28.40%)
    5 / 112 (4.46%)
         occurrences all number
    168
    7
    194
    5
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    3 / 365 (0.82%)
    2 / 26 (7.69%)
    4 / 507 (0.79%)
    4 / 112 (3.57%)
         occurrences all number
    3
    2
    4
    4
    DYSPNOEA
         subjects affected / exposed
    33 / 365 (9.04%)
    5 / 26 (19.23%)
    55 / 507 (10.85%)
    13 / 112 (11.61%)
         occurrences all number
    36
    8
    74
    16
    COUGH
         subjects affected / exposed
    44 / 365 (12.05%)
    4 / 26 (15.38%)
    104 / 507 (20.51%)
    20 / 112 (17.86%)
         occurrences all number
    57
    5
    128
    25
    RHINITIS ALLERGIC
         subjects affected / exposed
    5 / 365 (1.37%)
    0 / 26 (0.00%)
    12 / 507 (2.37%)
    8 / 112 (7.14%)
         occurrences all number
    5
    0
    12
    9
    PRODUCTIVE COUGH
         subjects affected / exposed
    3 / 365 (0.82%)
    2 / 26 (7.69%)
    12 / 507 (2.37%)
    3 / 112 (2.68%)
         occurrences all number
    3
    2
    15
    3
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    14 / 365 (3.84%)
    1 / 26 (3.85%)
    25 / 507 (4.93%)
    10 / 112 (8.93%)
         occurrences all number
    14
    1
    27
    10
    Psychiatric disorders
    INSOMNIA
         subjects affected / exposed
    34 / 365 (9.32%)
    3 / 26 (11.54%)
    31 / 507 (6.11%)
    21 / 112 (18.75%)
         occurrences all number
    39
    3
    33
    26
    DEPRESSION
         subjects affected / exposed
    21 / 365 (5.75%)
    2 / 26 (7.69%)
    20 / 507 (3.94%)
    8 / 112 (7.14%)
         occurrences all number
    22
    2
    20
    8
    ANXIETY
         subjects affected / exposed
    24 / 365 (6.58%)
    0 / 26 (0.00%)
    27 / 507 (5.33%)
    11 / 112 (9.82%)
         occurrences all number
    24
    0
    30
    12
    Investigations
    LYMPHOCYTE COUNT DECREASED
         subjects affected / exposed
    6 / 365 (1.64%)
    2 / 26 (7.69%)
    4 / 507 (0.79%)
    2 / 112 (1.79%)
         occurrences all number
    12
    2
    6
    2
    WEIGHT DECREASED
         subjects affected / exposed
    13 / 365 (3.56%)
    2 / 26 (7.69%)
    19 / 507 (3.75%)
    9 / 112 (8.04%)
         occurrences all number
    13
    2
    22
    9
    WEIGHT INCREASED
         subjects affected / exposed
    7 / 365 (1.92%)
    2 / 26 (7.69%)
    8 / 507 (1.58%)
    1 / 112 (0.89%)
         occurrences all number
    7
    3
    9
    1
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    44 / 365 (12.05%)
    0 / 26 (0.00%)
    14 / 507 (2.76%)
    4 / 112 (3.57%)
         occurrences all number
    93
    0
    21
    5
    Injury, poisoning and procedural complications
    INFUSION RELATED REACTION
         subjects affected / exposed
    25 / 365 (6.85%)
    1 / 26 (3.85%)
    58 / 507 (11.44%)
    29 / 112 (25.89%)
         occurrences all number
    35
    1
    73
    31
    Cardiac disorders
    PALPITATIONS
         subjects affected / exposed
    9 / 365 (2.47%)
    0 / 26 (0.00%)
    7 / 507 (1.38%)
    6 / 112 (5.36%)
         occurrences all number
    10
    0
    7
    6
    Nervous system disorders
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    21 / 365 (5.75%)
    3 / 26 (11.54%)
    18 / 507 (3.55%)
    5 / 112 (4.46%)
         occurrences all number
    22
    3
    23
    5
    PARAESTHESIA
         subjects affected / exposed
    46 / 365 (12.60%)
    3 / 26 (11.54%)
    37 / 507 (7.30%)
    8 / 112 (7.14%)
         occurrences all number
    50
    3
    44
    9
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    72 / 365 (19.73%)
    2 / 26 (7.69%)
    35 / 507 (6.90%)
    6 / 112 (5.36%)
         occurrences all number
    74
    2
    37
    12
    HYPOAESTHESIA
         subjects affected / exposed
    8 / 365 (2.19%)
    0 / 26 (0.00%)
    8 / 507 (1.58%)
    6 / 112 (5.36%)
         occurrences all number
    9
    0
    8
    7
    HEADACHE
         subjects affected / exposed
    31 / 365 (8.49%)
    3 / 26 (11.54%)
    66 / 507 (13.02%)
    25 / 112 (22.32%)
         occurrences all number
    49
    6
    81
    31
    DYSGEUSIA
         subjects affected / exposed
    24 / 365 (6.58%)
    0 / 26 (0.00%)
    23 / 507 (4.54%)
    5 / 112 (4.46%)
         occurrences all number
    26
    0
    24
    5
    DIZZINESS
         subjects affected / exposed
    17 / 365 (4.66%)
    0 / 26 (0.00%)
    45 / 507 (8.88%)
    20 / 112 (17.86%)
         occurrences all number
    20
    0
    55
    29
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    44 / 365 (12.05%)
    3 / 26 (11.54%)
    25 / 507 (4.93%)
    8 / 112 (7.14%)
         occurrences all number
    56
    5
    36
    16
    LEUKOPENIA
         subjects affected / exposed
    47 / 365 (12.88%)
    2 / 26 (7.69%)
    22 / 507 (4.34%)
    7 / 112 (6.25%)
         occurrences all number
    82
    2
    60
    11
    THROMBOCYTOPENIA
         subjects affected / exposed
    14 / 365 (3.84%)
    0 / 26 (0.00%)
    17 / 507 (3.35%)
    11 / 112 (9.82%)
         occurrences all number
    20
    0
    21
    13
    NEUTROPENIA
         subjects affected / exposed
    172 / 365 (47.12%)
    7 / 26 (26.92%)
    199 / 507 (39.25%)
    25 / 112 (22.32%)
         occurrences all number
    373
    16
    467
    41
    LYMPHOPENIA
         subjects affected / exposed
    19 / 365 (5.21%)
    1 / 26 (3.85%)
    7 / 507 (1.38%)
    1 / 112 (0.89%)
         occurrences all number
    30
    1
    22
    1
    Gastrointestinal disorders
    NAUSEA
         subjects affected / exposed
    128 / 365 (35.07%)
    7 / 26 (26.92%)
    100 / 507 (19.72%)
    72 / 112 (64.29%)
         occurrences all number
    202
    12
    147
    124
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    15 / 365 (4.11%)
    0 / 26 (0.00%)
    18 / 507 (3.55%)
    7 / 112 (6.25%)
         occurrences all number
    17
    0
    20
    7
    DYSPEPSIA
         subjects affected / exposed
    19 / 365 (5.21%)
    2 / 26 (7.69%)
    26 / 507 (5.13%)
    7 / 112 (6.25%)
         occurrences all number
    20
    2
    28
    8
    DIARRHOEA
         subjects affected / exposed
    50 / 365 (13.70%)
    6 / 26 (23.08%)
    184 / 507 (36.29%)
    37 / 112 (33.04%)
         occurrences all number
    66
    7
    309
    65
    CONSTIPATION
         subjects affected / exposed
    109 / 365 (29.86%)
    13 / 26 (50.00%)
    179 / 507 (35.31%)
    43 / 112 (38.39%)
         occurrences all number
    140
    15
    244
    62
    ABDOMINAL PAIN
         subjects affected / exposed
    29 / 365 (7.95%)
    2 / 26 (7.69%)
    77 / 507 (15.19%)
    12 / 112 (10.71%)
         occurrences all number
    41
    2
    98
    13
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    45 / 365 (12.33%)
    1 / 26 (3.85%)
    37 / 507 (7.30%)
    6 / 112 (5.36%)
         occurrences all number
    50
    1
    42
    6
    VOMITING
         subjects affected / exposed
    61 / 365 (16.71%)
    2 / 26 (7.69%)
    32 / 507 (6.31%)
    31 / 112 (27.68%)
         occurrences all number
    76
    3
    42
    56
    STOMATITIS
         subjects affected / exposed
    26 / 365 (7.12%)
    1 / 26 (3.85%)
    15 / 507 (2.96%)
    9 / 112 (8.04%)
         occurrences all number
    38
    1
    23
    10
    Skin and subcutaneous tissue disorders
    RASH MACULO-PAPULAR
         subjects affected / exposed
    5 / 365 (1.37%)
    1 / 26 (3.85%)
    19 / 507 (3.75%)
    6 / 112 (5.36%)
         occurrences all number
    5
    1
    20
    6
    RASH
         subjects affected / exposed
    22 / 365 (6.03%)
    1 / 26 (3.85%)
    141 / 507 (27.81%)
    19 / 112 (16.96%)
         occurrences all number
    26
    1
    194
    22
    PRURITUS
         subjects affected / exposed
    22 / 365 (6.03%)
    3 / 26 (11.54%)
    86 / 507 (16.96%)
    10 / 112 (8.93%)
         occurrences all number
    24
    3
    99
    15
    NIGHT SWEATS
         subjects affected / exposed
    4 / 365 (1.10%)
    2 / 26 (7.69%)
    18 / 507 (3.55%)
    11 / 112 (9.82%)
         occurrences all number
    4
    2
    19
    13
    ERYTHEMA
         subjects affected / exposed
    9 / 365 (2.47%)
    2 / 26 (7.69%)
    38 / 507 (7.50%)
    0 / 112 (0.00%)
         occurrences all number
    10
    3
    43
    0
    ALOPECIA
         subjects affected / exposed
    39 / 365 (10.68%)
    2 / 26 (7.69%)
    5 / 507 (0.99%)
    4 / 112 (3.57%)
         occurrences all number
    40
    2
    5
    4
    DRY SKIN
         subjects affected / exposed
    13 / 365 (3.56%)
    0 / 26 (0.00%)
    44 / 507 (8.68%)
    4 / 112 (3.57%)
         occurrences all number
    15
    0
    47
    6
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    52 / 365 (14.25%)
    4 / 26 (15.38%)
    79 / 507 (15.58%)
    24 / 112 (21.43%)
         occurrences all number
    57
    4
    90
    27
    BACK PAIN
         subjects affected / exposed
    49 / 365 (13.42%)
    5 / 26 (19.23%)
    75 / 507 (14.79%)
    11 / 112 (9.82%)
         occurrences all number
    63
    6
    87
    13
    BONE PAIN
         subjects affected / exposed
    37 / 365 (10.14%)
    1 / 26 (3.85%)
    22 / 507 (4.34%)
    3 / 112 (2.68%)
         occurrences all number
    42
    1
    22
    5
    MUSCLE SPASMS
         subjects affected / exposed
    16 / 365 (4.38%)
    2 / 26 (7.69%)
    70 / 507 (13.81%)
    3 / 112 (2.68%)
         occurrences all number
    20
    2
    81
    3
    MYALGIA
         subjects affected / exposed
    16 / 365 (4.38%)
    2 / 26 (7.69%)
    73 / 507 (14.40%)
    12 / 112 (10.71%)
         occurrences all number
    21
    2
    103
    15
    PAIN IN EXTREMITY
         subjects affected / exposed
    15 / 365 (4.11%)
    2 / 26 (7.69%)
    39 / 507 (7.69%)
    6 / 112 (5.36%)
         occurrences all number
    15
    2
    40
    7
    Infections and infestations
    FUNGAL INFECTION
         subjects affected / exposed
    3 / 365 (0.82%)
    2 / 26 (7.69%)
    5 / 507 (0.99%)
    3 / 112 (2.68%)
         occurrences all number
    3
    2
    5
    5
    CONJUNCTIVITIS
         subjects affected / exposed
    23 / 365 (6.30%)
    2 / 26 (7.69%)
    15 / 507 (2.96%)
    4 / 112 (3.57%)
         occurrences all number
    24
    2
    19
    4
    BRONCHITIS
         subjects affected / exposed
    79 / 365 (21.64%)
    5 / 26 (19.23%)
    83 / 507 (16.37%)
    6 / 112 (5.36%)
         occurrences all number
    104
    7
    126
    7
    GASTROENTERITIS
         subjects affected / exposed
    10 / 365 (2.74%)
    2 / 26 (7.69%)
    24 / 507 (4.73%)
    1 / 112 (0.89%)
         occurrences all number
    10
    2
    27
    1
    HERPES ZOSTER
         subjects affected / exposed
    14 / 365 (3.84%)
    0 / 26 (0.00%)
    8 / 507 (1.58%)
    11 / 112 (9.82%)
         occurrences all number
    14
    0
    9
    11
    INFLUENZA
         subjects affected / exposed
    17 / 365 (4.66%)
    2 / 26 (7.69%)
    23 / 507 (4.54%)
    2 / 112 (1.79%)
         occurrences all number
    17
    2
    25
    2
    NASOPHARYNGITIS
         subjects affected / exposed
    42 / 365 (11.51%)
    2 / 26 (7.69%)
    87 / 507 (17.16%)
    8 / 112 (7.14%)
         occurrences all number
    58
    2
    112
    10
    PHARYNGITIS
         subjects affected / exposed
    17 / 365 (4.66%)
    2 / 26 (7.69%)
    19 / 507 (3.75%)
    2 / 112 (1.79%)
         occurrences all number
    17
    2
    21
    2
    RHINITIS
         subjects affected / exposed
    34 / 365 (9.32%)
    0 / 26 (0.00%)
    56 / 507 (11.05%)
    0 / 112 (0.00%)
         occurrences all number
    41
    0
    69
    0
    SINUSITIS
         subjects affected / exposed
    20 / 365 (5.48%)
    2 / 26 (7.69%)
    42 / 507 (8.28%)
    11 / 112 (9.82%)
         occurrences all number
    24
    2
    50
    13
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    22 / 365 (6.03%)
    5 / 26 (19.23%)
    48 / 507 (9.47%)
    28 / 112 (25.00%)
         occurrences all number
    24
    7
    69
    37
    URINARY TRACT INFECTION
         subjects affected / exposed
    27 / 365 (7.40%)
    0 / 26 (0.00%)
    44 / 507 (8.68%)
    9 / 112 (8.04%)
         occurrences all number
    41
    0
    65
    10
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    14 / 365 (3.84%)
    1 / 26 (3.85%)
    19 / 507 (3.75%)
    10 / 112 (8.93%)
         occurrences all number
    19
    1
    20
    11

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Jun 2012
    Secondary endpoints updated.
    08 Feb 2016
    Changed the timing of CR/CRu at 120 weeks from N = 644 to all randomized subjects. Added an interim analysis for PFS Add CR at 120 weeks as the first secondary endpoint
    21 Apr 2016
    Re-insertion of Sections 13 .4 .1 and 13 .4 .2.
    25 Feb 2019
    Reduced the frequency of computed tomography (CT) scans during follow up (FU) visits.
    08 Jan 2024
    Included an additional criterion, which is time-driven, to the existing criterion, which is event-driven, to trigger the final progression-free survival (PFS; co-primary endpoint) analysis and therefore the end of the study.

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

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

    European Medicines Agency © 1995-Sun May 25 21:19:41 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA