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   43861   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A phase III, open-label, randomized, multicenter trial of ofatumumab maintenance treatment versus no further treatment in subjects with relapsed chronic lymphocytic leukemia (CLL) who have responded to induction therapy

    Summary
    EudraCT number
    		 2009-012518-39
    Trial protocol
    		 IT   NL   PL   BE   CZ   SE   FI   ES   FR   DK   HU   GR  
    Global end of trial date
    26 Jun 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Jul 2019
    First version publication date
    12 Jul 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    112517
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01039376
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Jun 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Jun 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate progression free survival (PFS) of subjects treated with ofatumumab maintenance treatment compared to no further treatment after remission induction in subjects with relapsed chronic CLL. Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 May 2010
    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
    Argentina: 4
    Country: Number of subjects enrolled
    Australia: 12
    Country: Number of subjects enrolled
    Belgium: 31
    Country: Number of subjects enrolled
    Brazil: 10
    Country: Number of subjects enrolled
    Canada: 16
    Country: Number of subjects enrolled
    Czech Republic: 29
    Country: Number of subjects enrolled
    Denmark: 17
    Country: Number of subjects enrolled
    Finland: 2
    Country: Number of subjects enrolled
    France: 26
    Country: Number of subjects enrolled
    Greece: 21
    Country: Number of subjects enrolled
    Hungary: 25
    Country: Number of subjects enrolled
    India: 5
    Country: Number of subjects enrolled
    Israel: 39
    Country: Number of subjects enrolled
    Italy: 31
    Country: Number of subjects enrolled
    Korea, Republic of: 4
    Country: Number of subjects enrolled
    Netherlands: 40
    Country: Number of subjects enrolled
    Norway: 2
    Country: Number of subjects enrolled
    Poland: 42
    Country: Number of subjects enrolled
    Russian Federation: 39
    Country: Number of subjects enrolled
    Spain: 10
    Country: Number of subjects enrolled
    Sweden: 9
    Country: Number of subjects enrolled
    Turkey: 9
    Country: Number of subjects enrolled
    Ukraine: 22
    Country: Number of subjects enrolled
    United States: 35
    Worldwide total number of subjects
    480
    EEA total number of subjects
    285
    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)
    240
    From 65 to 84 years
    238
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Eligible participants were stratified based on complete or partial remission at study entry, number of previous induction treatments (2 versus 3) and type of prior treatment (chemoimmunotherapy, only alkylating monotherapy, or other treatment). Participants were then randomized in a 1:1 ratio to receive ofatumumab or no further treatment.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ofatumumab
    Arm description
    		 Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.
    Arm type
    		 Experimental

    Investigational medicinal product name
    OMB157
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use, Intravenous drip use
    Dosage and administration details
    Ofatumumab infusions were given on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months.

    Arm title
    		 Observation
    Arm description
    		 Participants with relapsed CLL received no treatment and were under observation for up to 2 years.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		Ofatumumab Observation
    Started
    240
    240
    Completed
    110
    114
    Not completed
    130
    126
         Physician decision
    15
    10
         Consent withdrawn by subject
    20
    32
         Study terminated by Sponsor
    90
    72
         Lost to follow-up
    5
    12

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Ofatumumab
    Reporting group description
    		 Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.

    Reporting group title
    Observation
    Reporting group description
    		 Participants with relapsed CLL received no treatment and were under observation for up to 2 years.

    Reporting group values
    		 Ofatumumab Observation Total
    Number of subjects
    		 240 240 480
    Age Categorical
    Units: Subjects
        <=18 years
    		 0 0 0
        Between 18 and 65 years
    		 121 120 241
        >=65 years
    		 119 120 239
    Sex: Female, Male
    Units: Subjects
        Female
    		 79 80 159
        Male
    		 161 160 321
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic/Latino
    		 15 18 33
        Not Hispanic/Latino
    		 225 221 446
        Missing
    		 0 1 1
    AgeContinuous
    Units: Years
        arithmetic mean (standard deviation)
    		 63.9 ( 10.31 ) 64.1 ( 9.61 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Ofatumumab
    Reporting group description
    		 Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.

    Reporting group title
    Observation
    Reporting group description
    		 Participants with relapsed CLL received no treatment and were under observation for up to 2 years.

    Subject analysis set title
    Ofatumumab
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.

    Subject analysis set title
    Observation
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants with relapsed CLL received no treatment and were under observation for up to 2 years.

    Primary: Progression-free survival, as assessed by the Investigator

    		 Close Top of page
    End point title
    		 Progression-free survival, as assessed by the Investigator
    End point description
    Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause. PD was determined by the investigator according to the definitions of response in the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-Sponsored Working Group (NCI-WG) guidelines. According to the guidelines, PD is characterized by at least one of the following: lymphadenopathy (appearance of any new lesion such as enlarged lymph nodes (>1.5 centimeter [cm]), spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site); an increase by 50% or more in the previously noted enlargement of the liver or spleen; an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter; transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukemia.
    End point type
    Primary
    End point timeframe
    From randomization until progression or death (up to 79 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    240
    240
    Units: Months
        median (confidence interval 95%)
    34.17 (29.70 to 38.01)
    16.89 (12.98 to 20.37)
    Statistical analysis title
    		 PFS, as assessed by the investigator
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Stratified log rank test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 0.7

    Primary: Progression-free survival, as assessed by the Independent Review Committee (IRC)

    		 Close Top of page
    End point title
    		 Progression-free survival, as assessed by the Independent Review Committee (IRC)
    End point description
    Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause. PD was determined by the IRC according to the definitions of response in the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-Sponsored Working Group (NCI-WG) guidelines. According to the guidelines, PD is characterized by at least one of the following: lymphadenopathy (appearance of any new lesion such as enlarged lymph nodes (>1.5 centimeter [cm]), spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site); an increase by 50% or more in the previously noted enlargement of the liver or spleen; an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter; transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukemia.
    End point type
    Primary
    End point timeframe
    From randomization until progression or death (up to 79 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    240
    240
    Units: Months
        median (confidence interval 95%)
    33.74 (28.35 to 38.01)
    14.98 (11.63 to 19.12)
    Statistical analysis title
    		 PFS, as assessed by IRC
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Stratified log rank test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 0.68

    Secondary: Overall survival

    		 Close Top of page
    End point title
    		 Overall survival
    End point description
    Overall survival is defined as time from randomization to date of death.
    End point type
    Secondary
    End point timeframe
    From randomization until death (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    240
    240
    Units: Months
        median (confidence interval 95%)
    999 (68.96 to 999)
    73.63 (66.53 to 999)
    Statistical analysis title
    		 Overall survival
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6046
    Method
    		 Stratified log rank test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.25

    Secondary: Number of participants with improvement in response from Baseline

    		 Close Top of page
    End point title
    		 Number of participants with improvement in response from Baseline
    End point description
    Improvement in response was assessed by calculating the percentage of participants who changed from partial response (PR) at Baseline to complete response during the study.
    End point type
    Secondary
    End point timeframe
    From Baseline until the end of the study (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    193
    192
    Units: Participants
    16
    8
    No statistical analyses for this end point

    Secondary: Time to next therapy

    		 Close Top of page
    End point title
    		 Time to next therapy
    End point description
    Time to next therapy is defined as the time from randomization to the date of receiving the next CLL treatment.
    End point type
    Secondary
    End point timeframe
    From randomization until the end of the study (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    240
    240
    Units: Months
        median (confidence interval 95%)
    36.21 (30.49 to 41.40)
    27.56 (23.49 to 32.49)
    Statistical analysis title
    		 Time to next therapy
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0178
    Method
    		 Stratified log rank test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 0.96

    Secondary: Progression-free survival after next-line therapy

    		 Close Top of page
    End point title
    		 Progression-free survival after next-line therapy
    End point description
    Progression-free survival after next-line therapy is defined as the time from randomization until progression or death following the next-line therapy and counted as events deaths prior to next-line therapy. Participants who received next-line therapy and who did not have progression or death after next-line therapy were censored at their last date of contact. Participant who died prior to next-line therapy, was counted as an event.
    End point type
    Secondary
    End point timeframe
    From randomization until progression or death (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    168
    180
    Units: Months
        median (confidence interval 95%)
    999 (999 to 999)
    999 (999 to 999)
    Statistical analysis title
    		 Progression-free survival after next-line therapy
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    348
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3136
    Method
    		 log rank test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.42
         upper limit
    		 1.32

    Secondary: Time to progression after next-line therapy

    		 Close Top of page
    End point title
    		 Time to progression after next-line therapy
    End point description
    Time to progression after next-line therapy is defined as the time from progression following randomization until progression or death following next-line therapy and counted as events deaths prior to next-line therapy. Participants who received next-line therapy with a PD prior to receiving next line therapy and who did not had progression or death after next-line therapy were censored at their last date of contact. If a participant died prior to next-line therapy, this was counted as an event.
    End point type
    Secondary
    End point timeframe
    From randomization until progression or death (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    151
    170
    Units: Months
        median (confidence interval 95%)
    999 (999 to 999)
    999 (999 to 999)
    Statistical analysis title
    		 Time to progression after next-line therapy
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    321
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1603
    Method
    		 log rank test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.29
         upper limit
    		 1.19

    Secondary: Change from Baseline (BL) in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16)

    		 Close Top of page
    End point title
    		 Change from Baseline (BL) in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16)
    End point description
    The EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life (HRQoL) important in CLL. There are 4 multi-item scales – fatigue (2 items), treatment side effects ([TSE], 4 items), disease symptoms (disease effects scale [DES], 4 items), and infection (4 items) – and single-item scales (social activities [Social Problems (SP) Scale] and future health worries [Future Health (FH) Scale]). These are measured on a four-point Likert scale, where 1 = not at all and 4 = very much. These scores are transformed to give a rating from 0 – 100, where 0 = no symptoms or problems and 100 = severe symptoms or problems. Changes from Baseline were analyzed by a mixed model-repeated measures analysis of covariance (ANCOVA).
    End point type
    Secondary
    End point timeframe
    From randomization until the end of the study (up to 47 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    238
    236
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Disease Effects Scale
    0.36 ( 1.81 )
    2.56 ( 1.78 )
        Fatigue Scale
    -0.16 ( 2.96 )
    3.63 ( 2.93 )
        Future Health Scale
    -8.66 ( 3.69 )
    -5.08 ( 3.65 )
        Infection Scale
    0.77 ( 2.20 )
    0.25 ( 2.17 )
        Social Problems Scale
    5.69 ( 3.20 )
    10.02 ( 3.16 )
        Treatment Side Effects Scale
    -0.54 ( 1.77 )
    1.95 ( 1.74 )
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-CLL 16
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0199 [1]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.04
         upper limit
    		 -0.35
    Notes
    [1] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-CLL 16
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0085 [2]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.61
         upper limit
    		 -0.97
    Notes
    [2] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-CLL 16
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0642 [3]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.37
         upper limit
    		 0.21
    Notes
    [3] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-CLL 16
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6398 [4]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.67
         upper limit
    		 2.72
    Notes
    [4] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-CLL 16
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0055 [5]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.37
         upper limit
    		 -1.28
    Notes
    [5] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-CLL 16
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0063 [6]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.27
         upper limit
    		 -0.71
    Notes
    [6] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.

    Secondary: Change from Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) score

    		 Close Top of page
    End point title
    		 Change from Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) score
    End point description
    The EORTC QLQ-C30 is a self-reported, 30-item cancer-specific instrument that assesses 15 domains: physical functioning (5 items), role functioning (2 items), emotional functioning (4 items), cognitive functioning (2 items), social functioning (2 items), pain (2 items), fatigue (3 items), nausea and vomiting (2 items), five single-item symptom scores (insomnia, loss of appetite, constipation, diarrhea, and dyspnea), a single item asking about financial difficulties, and global health status/quality of life (QOF) consisting of 2 items. Functional and symptoms scales were measured on a four-point Likert scale, where 1 = not at all and 4 = very much, whereas global health status or QOF was assessed using a 7-item Likert scale, ranging from "poor" (worse quality of life) to "excellent" (better quality of life). Changes from Baseline were analyzed by mixed model-repeated measures ANCOVA.
    End point type
    Secondary
    End point timeframe
    From randomization until the end of the study (up to 47 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    238
    236
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Appetite Loss
    -0.63 ( 2.33 )
    0.85 ( 2.30 )
        Cognitive Functioning
    -1.63 ( 2.30 )
    -3.03 ( 2.29 )
        Constipation
    -1.71 ( 2.30 )
    0.27 ( 2.27 )
        Diarrhoea
    -1.99 ( 2.23 )
    -2.49 ( 2.20 )
        Dyspnoea
    0.44 ( 2.71 )
    2.76 ( 2.67 )
        Emotional Functioning
    -0.83 ( 2.47 )
    -4.72 ( 2.44 )
        Fatigue
    -0.02 ( 2.89 )
    4.61 ( 2.85 )
        Financial Difficulties
    4.09 ( 3.31 )
    5.85 ( 3.26 )
        Nausea and Vomiting
    0.28 ( 1.12 )
    1.50 ( 1.11 )
        Pain
    1.82 ( 2.89 )
    4.87 ( 2.87 )
        Physical Functioning
    -2.25 ( 2.01 )
    -4.07 ( 2.01 )
        Global Health Status/QOL
    -0.17 ( 2.52 )
    -1.94 ( 2.49 )
        Role Functioning
    -6.94 ( 3.04 )
    -10.51 ( 3.00 )
        Social Functioning
    -4.15 ( 2.71 )
    -7.80 ( 2.69 )
        Insomnia
    -4.49 ( 3.51 )
    -2.70 ( 3.48 )
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1816 [7]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.64
         upper limit
    		 0.69
    Notes
    [7] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2863 [8]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.18
         upper limit
    		 3.97
    Notes
    [8] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0932 [9]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.28
         upper limit
    		 0.33
    Notes
    [9] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6533 [10]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.67
         upper limit
    		 2.66
    Notes
    [10] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0963 [11]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.06
         upper limit
    		 0.42
    Notes
    [11] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0037 [12]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.27
         upper limit
    		 6.51
    Notes
    [12] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0013 [13]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.45
         upper limit
    		 -1.82
    Notes
    [13] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2902 [14]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.02
         upper limit
    		 1.51
    Notes
    [14] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0606 [15]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.49
         upper limit
    		 0.05
    Notes
    [15] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0393 [16]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.93
         upper limit
    		 -0.15
    Notes
    [16] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0968 [17]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.33
         upper limit
    		 3.96
    Notes
    [17] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1449 [18]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.61
         upper limit
    		 4.17
    Notes
    [18] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0259 [19]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 6.7
    Notes
    [19] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0175 [20]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    3.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 6.65
    Notes
    [20] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline (BL) in EORTC QLQ-C30
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3209 [21]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.33
         upper limit
    		 1.75
    Notes
    [21] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.

    Secondary: Change from Baseline in the Quality of Life Status as assessed by the EuroQol-5D (EQ-5D) Scale

    		 Close Top of page
    End point title
    		 Change from Baseline in the Quality of Life Status as assessed by the EuroQol-5D (EQ-5D) Scale
    End point description
    EQ-5D is comprised of a 5-item health status measure and a visual analogue scale (VAS) and is used to generate two scores: the utility score and the thermometer score. The utility score measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (level 1 = no problem; level 2 = some or moderate problem[s] and level 3 = unable, or extreme problems). Responses are typically converted into health utilities or valuations on a scale ranging from 0 (worst health) to 1 (perfect health). The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Changes from Baseline were analyzed by mixed model-repeated measures ANCOVA. A negative adjusted mean change from Baseline represents a worsening of quality of life.
    End point type
    Secondary
    End point timeframe
    From screening until the end of the study (up to 47 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    238
    236
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Utility Score
    -0.02 ( 0.03 )
    -0.05 ( 0.03 )
        Thermometer Score
    -0.37 ( 2.05 )
    -1.75 ( 2.04 )
    Statistical analysis title
    		 Change from Baseline in EQ-5D
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.011 [22]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.01
         upper limit
    		 0.06
    Notes
    [22] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.
    Statistical analysis title
    		 Change from Baseline in EQ-5D
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    474
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1999 [23]
    Method
    		 Repeated measures analysis of covariance
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.73
         upper limit
    		 3.49
    Notes
    [23] - The analysis is adjusted for BL score, actual strata, age group, BL ECOG performance status and Binet stage at Screening using mixed-model (Proc Mixed) repeated with intercept, BL score by time and treatment by time interaction.

    Secondary: Number of participants with an improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status at the indicated time points

    		 Close Top of page
    End point title
    		 Number of participants with an improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status at the indicated time points
    End point description
    Improvement is defined as a decrease from Baseline by at least one step on the ECOG performance status scale (improvement categorized as yes or no). Improvement in ECOG performance status was measured.
    End point type
    Secondary
    End point timeframe
    From randomization until the end of the study (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    240
    240
    Units: Participants
        C1 W2/M1 (n=234, 202)
    10
    12
        C2 W9/M3 (n= 226, 222)
    20
    17
        C3 W17/M5 (n=214, 203)
    16
    17
        C4 W25/M7 (n=200, 184)
    18
    16
        C5 W33/M9 (n=194, 171)
    16
    18
        C6 W41/M11 (n=183, 151)
    14
    12
        C7 W49/M13 (n= 174, 137)
    18
    14
        C8 W57/M15 (n=154, 119)
    14
    15
        C9 W65/M17 (n=140, 107)
    11
    12
        C10 W73/M19 (n=136, 103)
    14
    10
        C11 W81/M21 (n= 124, 94)
    10
    9
        C12 W89/M23 (n= 119, 82)
    11
    7
        C13 W97/M25 (n=112, 79)
    9
    7
        3M FU (n=106, 63)
    11
    6
        6M FU (n=104, 61)
    9
    4
        9M FU (n=92, 50)
    5
    5
        12M FU (n=81, 43)
    6
    5
        15M FU (n=66, 39)
    4
    4
        18M FU (n=60, 35)
    4
    3
        21M FU (n=51, 32)
    3
    3
        24M FU (n=48, 26)
    3
    2
        27M FU (n=40, 24)
    3
    1
        30M FU (n=35, 18)
    3
    1
        33M FU (n=30, 17)
    3
    1
        36M FU (n=27, 15)
    3
    1
        39M FU (n=22, 12)
    1
    2
        42M FU (n=17, 10)
    0
    0
        45M FU (n=14, 7)
    0
    1
        48M FU (n=10, 5)
    0
    1
        51M FU (n=8, 4)
    0
    1
        54M FU (n=6, 2)
    1
    1
        57M FU (n=3, 2)
    0
    1
        60M FU (n=2, 2)
    0
    1
        Withdrawal (n=79, 94)
    5
    10
        Worst-Case Post Baseline
    3
    5
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated constitutional or B-symptoms at the indicated time points

    		 Close Top of page
    End point title
    		 Number of participants with the indicated constitutional or B-symptoms at the indicated time points
    End point description
    Participants with the indicated constitutional or B-symptoms (night sweats [without signs of infection]; unintentional weight loss >= 10% within the previous 6 months; recurrent, unexplained fever of > 38 degrees celcius or 100.5 degrees fahrenheit for 2 weeks; and extreme fatigue) were presented. The proportion of participants with no night sweats, no weight loss, no fever and no extreme fatigue were summarized.
    End point type
    Secondary
    End point timeframe
    From Screening until the end of the study (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    240
    240
    Units: Participants
        SCR, extreme fatigue
    0
    7
        SCR, fever
    0
    1
        SCR, night sweats
    13
    8
        SCR, weight loss
    2
    1
        C1 W2/M1, extreme fatigue (n=236, 204)
    0
    2
        C1 W2/M1, fever (n=236, 204)
    0
    0
        C1 W2/M1, night sweats (n=236, 204)
    9
    6
        C1 W2/M1, weight loss (n=236, 204)
    4
    1
        C2 W9/M3, extreme fatigue (n=227, 223)
    3
    3
        C2 W9/M3, fever (n=227, 223)
    1
    2
        C2 W9/M3, night sweats (n=227, 223)
    6
    10
        C2 W9/M3, weight loss (n=227, 223)
    3
    1
        C3 W17/M5, extreme fatigue (n=215, 206)
    4
    5
        C3 W17/M5, fever (n=215, 206)
    1
    2
        C3 W17/M5, night sweats (n=215, 206)
    6
    10
        C3 W17/M5, weight loss (n=215, 206)
    3
    3
        C4 W25/M7, extreme fatigue (n=203, 187)
    1
    3
        C4 W25/M7, fever (n=203, 187)
    1
    2
        C4 W25/M7, night sweats (n=203, 187)
    5
    7
        C4 W25/M7, weight loss (n=203, 187)
    1
    1
        C5 W33/M9, extreme fatigue (n=196, 171)
    1
    5
        C5 W33/M9, fever (n=196, 171)
    1
    0
        C5 W33/M9, night sweats fatigue (n=196, 171)
    7
    8
        C5 W33/M9, weight loss (n=196, 171)
    0
    4
        C6 W41/M11, extreme fatigue (n=184, 152)
    1
    2
        C6 W41/M11, fever (n=184, 152)
    2
    0
        C6 W41/M11, night sweats (n=184, 152)
    7
    7
        C6 W41/M11, weight loss (n=184, 152)
    0
    0
        C7 W49/M13, extreme fatigue (n=175, 138)
    1
    1
        C7 W49/M13, fever (n=175, 138)
    0
    0
        C7 W49/M13, night sweats (n=175, 138)
    3
    5
        C7 W49/M13, weight loss (n=175, 138)
    2
    1
        C8 W57/M15, extreme fatigue (n=155, 122)
    1
    1
        C8 W57/M15, fever (n=155, 122)
    2
    0
        C8 W57/M15, night sweats (n=155, 122)
    4
    4
        C8 W57/M15, weight loss (n=155, 122)
    2
    3
        C9 W65/M17, extreme fatigue (n=142, 107)
    2
    2
        C9 W65/M17, fever (n=142, 107)
    2
    0
        C9 W65/M17, night sweats (n=142, 107)
    7
    4
        C9 W65/M17, weight loss (n=142, 107)
    1
    2
        C10 W73/M19, extreme fatigue (n=137, 103)
    2
    2
        C10 W73/M19, fever (n=137, 103)
    1
    0
        C10 W73/M19, night sweats (n=137, 103)
    7
    4
        C10 W73/M19, weight loss (n=137, 103)
    2
    1
        C11 W81/M21, extreme fatigue (n=126, 96)
    0
    3
        C11 W81/M21, fever (n=126, 96)
    1
    0
        C11 W81/M21, night sweats (n=126, 96)
    2
    4
        C11 W81/M21, weight loss (n=126, 96)
    0
    0
        C12 W89/M23, extreme fatigue (n=121, 84)
    1
    0
        C12 W89/M23, fever (n=121, 84)
    0
    0
        C12 W89/M23, night sweats (n=121, 84)
    3
    3
        C12 W89/M23, weight loss (n=121, 84)
    0
    1
        C13 W97/M25, extreme fatigue (n=114, 79)
    1
    0
        C13 W97/M25, fever (n=114, 79)
    0
    0
        C13 W97/M25, night sweats (n=114, 79)
    2
    1
        C13 W97/M25, weight loss (n=114, 79)
    1
    3
        3M follow up, extreme fatigue (n=112, 64)
    3
    2
        3M follow up, fever (n=112, 64)
    1
    1
        3M follow up, night sweats (n=112, 64)
    4
    4
        3M follow up, weight loss (n=112, 64)
    2
    0
        6M follow up, extreme fatigue (n=106, 61)
    3
    2
        6M follow up, fever (n=106, 61)
    1
    0
        6M follow up, night sweats (n=106, 61)
    2
    2
        6M follow up, weight loss (n=106, 61)
    1
    1
        9M follow up, extreme fatigue (n=94, 50)
    2
    2
        9M follow up, fever (n=94, 50)
    0
    0
        9M follow up, night sweats (n=94, 50)
    4
    2
        9M follow up, weight loss (n=94, 50)
    0
    2
        12M follow up, extreme fatigue (n=82, 45)
    0
    3
        12M follow up, fever (n=82, 45)
    1
    1
        12M follow up, night sweats (n=82, 45)
    2
    4
        12M follow up, weight loss (n=82, 45)
    0
    1
        15M follow up, extreme fatigue (n=68, 41)
    0
    0
        15M follow up, fever (n=68, 41)
    0
    1
        15M follow up, night sweats (n=68, 41)
    2
    1
        15M follow up, weight loss (n=68, 41)
    1
    0
        18M follow up, extreme fatigue (n=62, 35)
    1
    1
        18M follow up, fever (n=62, 35)
    0
    0
        18M follow up, night sweats (n=62, 35)
    2
    1
        18M follow up, weight loss (n=62, 35)
    0
    0
        21M follow up, extreme fatigue (n=53, 33)
    0
    1
        21M follow up, fever (n=53, 32)
    0
    0
        21M follow up, night sweats (n=53, 32)
    1
    2
        21M follow up, weight loss (n=53, 33)
    0
    0
        27M follow up, extreme fatigue (n=40, 25)
    0
    0
        27M follow up, fever (n=40, 25)
    0
    0
        27M follow up, night sweats (n=40, 24)
    2
    1
        27M follow up, weight loss (n=40, 25)
    1
    1
        30M follow up, extreme fatigue (n=35, 18)
    0
    0
        30M follow up, fever (n=35, 18)
    0
    0
        30M follow up, night sweats (n=35, 18)
    1
    1
        30M follow up, weight loss (n=35, 18)
    0
    0
        33M follow up, extreme fatigue (n=30, 17)
    0
    0
        33M follow up, fever (n=30, 17)
    1
    0
        33M follow up, night sweats (n=30, 17)
    2
    2
        33M follow up, weight loss (n=30, 17)
    0
    0
        36M follow up, extreme fatigue (n=27, 15)
    1
    0
        36M follow up, fever (n=27, 15)
    0
    0
        36M follow up, night sweats (n=27, 15)
    1
    0
        36M follow up, weight loss (n=27, 15)
    0
    0
        39M follow up, extreme fatigue (n=23, 12)
    1
    0
        39M follow up, fever (n=23, 12)
    0
    0
        39M follow up, night sweats (n=23, 12)
    1
    0
        39M follow up, weight loss (n=23, 12)
    0
    0
        42M follow up, extreme fatigue (n=18, 10)
    0
    0
        42M follow up, fever (n=18, 10)
    0
    1
        42M follow up, night sweats (n=18, 10)
    0
    1
        42M follow up,, weight loss (n=18, 10)
    0
    0
        51M follow up, extreme fatigue (n=8, 4)
    0
    0
        51M follow up, fever (n=8, 4)
    1
    0
        51M follow up, night sweats (n=8, 4)
    0
    1
        51M follow up, weight loss (n=8, 4)
    0
    0
        54M follow up, extreme fatigue (n=6, 2)
    0
    0
        54M follow up, fever (n=6, 2)
    1
    0
        54M follow up, night sweats (n=6, 2)
    0
    0
        54M follow up, weight loss (n=6, 2)
    0
    0
        Withdrawal, extreme fatigue (n=81, 97)
    9
    12
        Withdrawal, fever (n=81, 97)
    7
    3
        Withdrawal, night sweats (n=81, 97)
    14
    15
        Withdrawal, weight loss (n=81, 97)
    4
    10
    No statistical analyses for this end point

    Secondary: Number of participants with Grade 3 and above adverse event of infection

    		 Close Top of page
    End point title
    		 Number of participants with Grade 3 and above adverse event of infection
    End point description
    Participants with Grade 3, Grade 4 and Grade 5 adverse event of infection are presented. Adverse events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) grade, version 4.0 (1=mild; 2=moderate; 3=severe; 4=life-threatening/disabling; 5=death).
    End point type
    Secondary
    End point timeframe
    From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 (up to 26 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    239
    241
    Units: Participants
    38
    23
    No statistical analyses for this end point

    Secondary: Number of participants with any adverse event (AE) or serious adverse event (SAE)

    		 Close Top of page
    End point title
    		 Number of participants with any adverse event (AE) or serious adverse event (SAE)
    End point description
    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
    End point type
    Secondary
    End point timeframe
    From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until end of study for SAEs (88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    239
    241
    Units: Participants
        Any AE
    221
    198
        Any SAE
    120
    120
    No statistical analyses for this end point

    Secondary: Number of participants with a Grade 3 or Grade 4 myelosuppression (anemia, neutropenia, or thrombocytopenia) at indicated time points

    		 Close Top of page
    End point title
    		 Number of participants with a Grade 3 or Grade 4 myelosuppression (anemia, neutropenia, or thrombocytopenia) at indicated time points
    End point description
    Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. Number of participants who reported myelosuppression (anemia [low hemoglobin count], neutropenia [low neutrophil count], and thrombocytopenia [low platelet count]) are presented. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 4.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).
    End point type
    Secondary
    End point timeframe
    From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until the end of the study for SAEs (88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    239
    241
    Units: Participants
        SCR (n=221, 199)
    7
    5
        C1 W1/M1 (n=3, 10)
    1
    1
        C1 W2/M1 (n=225, 192)
    13
    8
        C2 W9/M3 (n=221, 210)
    12
    15
        C2, unscheduled (n=5, 2)
    1
    0
        C3 W17/M5 9 (n=208, 195)
    18
    7
        C3, unscheduled (n=7, 2)
    1
    0
        C4 W25/M7 (n=192, 180)
    12
    8
        C4 Unscheduled (n= 1, 0)
    1
    0
        C5 W33/M9, (n= 188, 164)
    15
    5
        C5, unscheduled (n= 3, 0)
    1
    0
        C6 W41/M11 (n=180, 139)
    13
    5
        C6 unscheduled (n= 8, 0)
    4
    0
        C6 unscheduled (n= 1, 0)
    1
    0
        C7 W49/M13 (n= 165, 132)
    9
    2
        C8 W57/M15 (n=148, 120)
    10
    3
        C9 W65/M17 (n=135, 101)
    5
    1
        C9, unscheduled (n= 2, 1)
    0
    1
        C10 W73/M19 (n=130, 101)
    2
    2
        C11 W81/M21 (n=122, 92)
    5
    1
        C11 unscheduled (n=2, 1)
    1
    0
        C11 unscheduled (n=2, 0)
    1
    0
        C12 W89/M23 (n= 115, 81)
    3
    2
        C13 W97/M25 (n=109, 75)
    3
    2
        C13, unscheduled (n=2, 0)
    1
    0
        3M follow-up (n=102, 61)
    2
    1
        6M follow-up (n=92, 55)
    2
    1
        9M follow-up (n=86, 50)
    2
    1
        12M follow-up (n=77, 43)
    1
    2
        15M follow-up (n=62, 37)
    1
    0
        18M follow-up (n=55, 33)
    0
    1
        27M follow-up (n=37, 22)
    0
    1
        30M follow-up (n=29, 17)
    0
    1
        33M follow-up (n=27, 16)
    1
    0
        60M follow-up (n=2, 2)
    1
    0
        Withdrawal (n=76, 93)
    11
    8
        Unscheduled (n=2, 2)
    0
    1
        Unscheduled (n=2, 5)
    0
    2
        Unscheduled (n=7, 7)
    1
    0
    No statistical analyses for this end point

    Secondary: Number of participants who received at least one transfusion during the study

    		 Close Top of page
    End point title
    		 Number of participants who received at least one transfusion during the study
    End point description
    Participants who received at least one transfusion (any blood products or blood supportive care product) during the study are presented.
    End point type
    Secondary
    End point timeframe
    From randomization until the end of the study (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    239
    241
    Units: Participants
    96
    64
    No statistical analyses for this end point

    Secondary: Number of participants diagnosed with autoimmune hemolytic anemia (AIHA)

    		 Close Top of page
    End point title
    		 Number of participants diagnosed with autoimmune hemolytic anemia (AIHA)
    End point description
    AIHA is a disease where the body's immune system fails to recognize red blood cells as "self" and begins destroying these red blood cells. The number of participants diagnosed with AIHA are presented.
    End point type
    Secondary
    End point timeframe
    From randomization until the end of the study (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    239
    241
    Units: Participants
        Haemolytic anaemia
    2
    2
        Autoimmune haemolytic anaemia
    1
    4
        Thrombocytopenic purpura
    0
    1
    No statistical analyses for this end point

    Secondary: Number of participants with a positive anti-ofatumumab antibody (human anti-human antibody; HAHA) result

    		 Close Top of page
    End point title
    		 Number of participants with a positive anti-ofatumumab antibody (human anti-human antibody; HAHA) result
    End point description
    All serum samples for analysis of HAHA were first tested in a screening step; positive samples from the screening were further evaluated in a confirmation test. The confirmed positive samples were reported as HAHA positive and further evaluated in the titration test to obtain a titer of HAHA. A confirmed positive result at any time point means the participant is positive for HAHA.Results are reported as the number of participants positive for HAHA.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Visit 1), Months 7, 13, 19, and 25 during treatment and at 3 and 6 months after last ofatumumab dose (up to 30 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    239
    0 [24]
    Units: Participants
    1
    Notes
    [24] - analysis not done for this group
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in the immunoglobulin (Ig) antibodies IgA, IgG, and IgM at indicated time points

    		 Close Top of page
    End point title
    		 Mean change from Baseline in the immunoglobulin (Ig) antibodies IgA, IgG, and IgM at indicated time points
    End point description
    Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants. Baseline IgA, IgG, and IgM values are the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-baseline value minus the Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline, every six months during treatment, and after last treatment visit and/or upon relapse (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    239
    241
    Units: grams per liter
    arithmetic mean (standard deviation)
        IgA, C2 W9, M3 (n=0, 2)
    0.0 ( 0.0 )
    0.2 ( 0.23 )
        IgA, C3 W17, M5 (n=6, 3)
    0.0 ( 0.12 )
    -0.1 ( 0.24 )
        IgA, C4 W25, M7 (n=189, 172)
    -0.1 ( 0.17 )
    -0.0 ( 0.41 )
        IgA, C5 W33, M9 (n= 1, 2)
    -0.0 ( 999 )
    -0.0 ( 0.01 )
        IgA, C6 W41, M11 (n=1,1)
    0.0 ( 999 )
    -0.1 ( 999 )
        IgA, C7 W49, M13 (n=157, 122)
    -0.1 ( 0.24 )
    -0.0 ( 0.63 )
        IgA, C8 W57, M15 (n=3, 2)
    -0.1 ( 0.15 )
    0.0 ( 0.02 )
        IgA, C9 W65, M17 (n=3, 2)
    -0.2 ( 0.17 )
    0.1 ( 0.04 )
        IgA, C10 W73, M19 (n=125, 91)
    -0.1 ( 0.20 )
    0.1 ( 0.37 )
        IgA, C11 W81, M21 (n=1, 2)
    -0.0 ( 999 )
    0.2 ( 0.21 )
        IgA, C12 W89, M23 (n=1, 4)
    -0.3 ( 999 )
    0.2 ( 0.39 )
        IgA, C13 W97, M25 (n=107, 74)
    -0.1 ( 0.23 )
    0.1 ( 0.38 )
        IgA, 3M FU (n=89, 51)
    -0.1 ( 0.22 )
    0.2 ( 0.37 )
        IgA, 6M FU (n=83, 50)
    -0.1 ( 0.18 )
    0.1 ( 0.39 )
        IgA, 9M FU (n=62, 40)
    -0.1 ( 0.22 )
    0.1 ( 0.38 )
        IgA, 12M FU (n=54, 35)
    -0.1 ( 0.30 )
    0.2 ( 0.36 )
        IgA, 15M FU (n=40, 31)
    -0.0 ( 0.27 )
    0.2 ( 0.44 )
        IgA, 18M FU (n=38, 23)
    0.1 ( 0.57 )
    0.1 ( 0.25 )
        IgA, 21M FU (n=33, 23)
    -0.1 ( 0.40 )
    0.1 ( 0.34 )
        IgA, 24M FU (n=29, 21)
    0.2 ( 1.06 )
    0.1 ( 0.37 )
        IgA, 27M FU (n=24, 15)
    0.1 ( 0.70 )
    0.1 ( 0.46 )
        IgA, 30M FU (n=18, 12)
    0.2 ( 0.85 )
    0.1 ( 0.58 )
        IgA, 33M FU (n=18, 11)
    0.4 ( 1.48 )
    0.2 ( 0.60 )
        IgA, 36M FU (n=18, 11)
    0.2 ( 1.06 )
    0.2 ( 0.63 )
        IgA, 39M FU (n= 14, 8)
    0.2 ( 0.86 )
    0.3 ( 0.71 )
        IgA, 42M FU (n=14, 6)
    0.4 ( 1.67 )
    0.2 ( 0.72 )
        IgA, 45M FU (n=11, 4)
    -0.2 ( 0.20 )
    0.4 ( 0.94 )
        IgA, 48M FU (n=9, 3)
    -0.1 ( 0.83 )
    -0.0 ( 0.25 )
        IgA, 51M FU (n=4, 3)
    0.3 ( 1.15 )
    0.2 ( 0.70 )
        IgA, 54M FU (n=6, 2)
    0.0 ( 0.89 )
    0.7 ( 1.34 )
        IgA, 57M FU (n=3, 2)
    -0.4 ( 0.36 )
    0.4 ( 1.04 )
        IgA, 60M FU (n=2, 2)
    -0.5 ( 0.42 )
    0.4 ( 1.05 )
        IgA, Withdrawal (n=6, 4)
    0.0 ( 0.53 )
    -0.1 ( 0.08 )
        IgG, C2 W9, M3 (n=0, 2)
    0.0 ( 0.0 )
    -0.4 ( 0.21 )
        IgG, C3 W17, M5 (n=6, 3)
    0.0 ( 1.17 )
    0.2 ( 0.39 )
        IgG, C4 W25, M7 (n=190, 172)
    -0.7 ( 2.03 )
    -0.1 ( 1.83 )
        IgG, C5 W33, M9 (n= 1, 2)
    -1.0 ( 999 )
    0.5 ( 2.20 )
        IgG, C6 W41, M11 (n=1,1)
    -1.9 ( 999 )
    1.0 ( 999 )
        IgG, C7 W49, M13 (n=157, 122)
    -1.1 ( 1.9 )
    0.2 ( 2.88 )
        IgG, C8 W57, M15 (n=3, 2)
    -1.3 ( 1.03 )
    -0.9 ( 0.08 )
        IgG, C9 W65, M17 (n=3, 2)
    -3.7 ( 4.96 )
    0.9 ( 0.71 )
        IgG, C10 W73, M19 (n=125, 91)
    -1.0 ( 2.15 )
    0.6 ( 4.61 )
        IgG, C11 W81, M21 (n=1, 2)
    0.2 ( 999 )
    -0.3 ( 1.39 )
        IgG, C12 W89, M23 (n=1, 4)
    -0.5 ( 999 )
    0.2 ( 0.89 )
        IgG, C13 W97, M25 (n=107, 74)
    -1.1 ( 2.45 )
    0.3 ( 3.02 )
        IgG, 3M FU (n=90, 51)
    -0.7 ( 2.46 )
    0.2 ( 2.83 )
        IgG, 6M FU (n=83, 50)
    -0.9 ( 2.24 )
    0.2 ( 2.89 )
        IgG, 9M FU (n=62, 40)
    -0.7 ( 2.29 )
    0.1 ( 2.87 )
        IgG, 12M FU (n=54, 35)
    -0.5 ( 2.17 )
    -0.3 ( 3.26 )
        IgG, 15M FU (n=40, 31)
    -0.4 ( 2.49 )
    -0.1 ( 3.29 )
        IgG, 18M FU (n=38, 23)
    -0.5 ( 2.71 )
    -0.3 ( 3.45 )
        IgG, 21M FU (n=33, 23)
    -0.9 ( 2.39 )
    0.1 ( 3.81 )
        IgG, 24M FU (n=29, 21)
    -0.1 ( 2.17 )
    0.0 ( 3.43 )
        IgG, 27M FU (n=24, 15)
    -0.3 ( 2.32 )
    -0.5 ( 3.97 )
        IgG, 30M FU (n=18, 12)
    0.3 ( 2.67 )
    -0.9 ( 4.83 )
        IgG, 33M FU (n= 18, 11)
    0.7 ( 2.91 )
    -1.1 ( 5.63 )
        IgG, 36M FU (n=18, 11)
    -0.1 ( 2.71 )
    -1.2 ( 3.87 )
        IgG, 39M FU (n= 14, 8)
    0.3 ( 2.53 )
    -0.9 ( 5.60 )
        IgG, 42M FU (n= 14, 6)
    0.6 ( 3.03 )
    0.9 ( 4.82 )
        IgG, 45M FU (n=11, 4)
    -0.6 ( 2.11 )
    2.3 ( 4.00 )
        IgG, 48M FU (n= 9, 3)
    -0.6 ( 2.30 )
    3.5 ( 3.14 )
        IgG, 51M FU (n=4, 3)
    0.1 ( 3.25 )
    2.4 ( 4.02 )
        IgG, 54M FU (n=6, 2)
    -1.0 ( 2.35 )
    5.6 ( 4.14 )
        IgG, 57M FU (n=3, 2)
    1.3 ( 4.01 )
    5.3 ( 5.68 )
        IgG, 60M FU (n=2, 2)
    0.8 ( 4.43 )
    4.6 ( 4.28 )
        IgG, Withdrawal (n=6, 4)
    -0.7 ( 0.91 )
    -1.5 ( 1.86 )
        IgM, C2 W9, M3 (n=0, 2)
    0.0 ( 0.0 )
    0.1 ( 0.12 )
        IgM, C3 W17, M5 (n=6, 3)
    -0.0 ( 0.09 )
    -0.0 ( 0.06 )
        IgM, C4 W25, M7 (n=190, 172)
    -0.1 ( 0.43 )
    0.1 ( 0.42 )
        IgM, C5 W33, M9 (n= 1, 2)
    -0.1 ( 999 )
    -0.1 ( 0.07 )
        IgM, C6 W41, M11 (n=1,1)
    -0.5 ( 999 )
    0.0 ( 999 )
        IgM, C7 W49, M13 (n=157, 122)
    -0.1 ( 0.29 )
    0.2 ( 0.90 )
        IgM, C8 W57, M15 (n=3, 2)
    -0.0 ( 0.05 )
    -0.0 ( 0.01 )
        IgM, C9 W65, M17 (n= 3, 2)
    -0.3 ( 0.54 )
    0.3 ( 0.49 )
        IgM, C10 W73, M19 (n=125, 91)
    -0.1 ( 0.36 )
    0.2 ( 0.86 )
        IgM, C11 W81, M21 (n=1, 2)
    0.0 ( 999 )
    0.2 ( 0.04 )
        IgM, C12 W89, M23 (n=1, 4)
    0.0 ( 999 )
    -0.0 ( 0.11 )
        IgM, C13 W97, M25 (n=107, 74)
    -0.1 ( 0.45 )
    0.2 ( 0.79 )
        IgM, 3M FU (n=90, 51)
    -0.0 ( 0.35 )
    0.3 ( 1.30 )
        IgM, 6M FU (n=83, 50)
    -0.1 ( 0.36 )
    0.4 ( 1.60 )
        IgM, 9M FU (n=62, 40)
    -0.1 ( 0.17 )
    0.6 ( 2.93 )
        IgM, 12M FU (n=54, 35)
    -0.0 ( 0.18 )
    0.6 ( 2.49 )
        IgM, 15M FU (n=40, 31)
    -0.0 ( 0.15 )
    0.3 ( 1.08 )
        IgM, 18M FU (n=38, 23)
    0.1 ( 0.25 )
    1.2 ( 4.95 )
        IgM, 21M FU (n=33, 23)
    0.1 ( 0.41 )
    1.4 ( 5.48 )
        IgM, 24M FU (n=29, 21)
    0.0 ( 0.14 )
    2.0 ( 8.19 )
        IgM, 27M FU (n=24, 15)
    0.2 ( 0.41 )
    -0.2 ( 1.14 )
        IgM, 30M FU (n=18, 12)
    0.1 ( 0.17 )
    -0.0 ( 1.51 )
        IgM, 33M FU (n=18, 11)
    0.1 ( 0.22 )
    0.1 ( 0.36 )
        IgM, 36M FU (n=18, 11)
    0.2 ( 0.28 )
    -0.3 ( 1.31 )
        IgM, 39M FU (n=14, 8)
    0.1 ( 0.21 )
    -0.4 ( 1.54 )
        IgM, 42M FU (n=14, 6)
    0.1 ( 0.23 )
    -0.6 ( 1.79 )
        IgM, 45M FU (n=11, 4)
    0.2 ( 0.32 )
    0.2 ( 0.27 )
        IgM, 48M FU (n=9, 3)
    0.1 ( 0.28 )
    0.4 ( 0.38 )
        IgM, 51M FU (n=4, 3)
    -0.0 ( 0.06 )
    0.3 ( 0.39 )
        IgM, 54M FU (n=6, 2)
    0.1 ( 0.24 )
    0.5 ( 0.26 )
        IgM, 57M FU (n=3, 2)
    0.2 ( 0.49 )
    0.4 ( 0.41 )
        IgM, 60M FU (n=2, 2)
    0.6 ( 0.84 )
    0.4 ( 0.42 )
        IgM, Withdrawal (n=6, 4)
    0.3 ( 0.73 )
    -0.0 ( 0.03 )
    No statistical analyses for this end point

    Secondary: Number of participants who were positive and negative for minimal residual disease (MRD) at any visit

    		 Close Top of page
    End point title
    		 Number of participants who were positive and negative for minimal residual disease (MRD) at any visit
    End point description
    MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment at the time the participant achieved a confirmed complete remission. Number of participants who were positive and negative for minimal residual disease (MRD) at any visit is presented.
    End point type
    Secondary
    End point timeframe
    From randomization until the end of the study (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    240
    240
    Units: Participants
        Positive
    150
    122
        Negative
    27
    37
    No statistical analyses for this end point

    Secondary: Change from Baseline in cluster of differentiation (CD) CD5+CD19+ and CD5-CD19+ cell counts at the indicated time points

    		 Close Top of page
    End point title
    		 Change from Baseline in cluster of differentiation (CD) CD5+CD19+ and CD5-CD19+ cell counts at the indicated time points
    End point description
    CD5+CD19+ cells were counted by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline CD5+CD19+ and CD5-CD19+ cell count value is the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
    End point type
    Secondary
    End point timeframe
    Baseline and every two months from Month 3 until Month 25 and at every followup (up to 88 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    240
    240
    Units: Cells per microliter
    arithmetic mean (standard deviation)
        CD5+CD19+, C2 W9, M3 (n=192, 166)
    -284.1 ( 2101.26 )
    598.6 ( 3155.69 )
        CD5+CD19+, C3 W17, M5 (n=185, 169)
    52.0 ( 3554.94 )
    750.5 ( 1995.47 )
        CD5+CD19+, C4 W25, M7 (n=170, 152)
    -177.6 ( 4105.41 )
    2102.2 ( 9866.31 )
        CD5+CD19+, C5 W33, M9 (n= 168, 147)
    -113.6 ( 3336.44 )
    1905.2 ( 6104.84 )
        CD5+CD19+, C6 W41, M11 (n=154, 129)
    -450.3 ( 2851.41 )
    1550.9 ( 5483.76 )
        CD5+CD19+, C7 W49, M13 (n=152, 122)
    -505.3 ( 2716.66 )
    1429.2 ( 4408.69 )
        CD5+CD19+, C8 W57, M15 (n=137, 108)
    -625.9 ( 3003.35 )
    1107.6 ( 3371.04 )
        CD5+CD19+, C9 W65, M17 (n=123, 90)
    -649.5 ( 3057.32 )
    967.0 ( 1826.90 )
        CD5+CD19+, C10 W73, M19 (n=120, 89)
    -238.6 ( 4061.13 )
    1146.0 ( 1914.02 )
        CD5+CD19+, C11 W81, M21 (n=112, 89)
    -579.0 ( 3446.95 )
    1656.7 ( 2662.28 )
        CD5+CD19+, C12 W89, M23, (n=110, 74)
    -569.5 ( 3510.43 )
    1608.3 ( 3220.20 )
        CD5+CD19+, C13 W97, M25 (n=100, 64)
    -361.3 ( 2702.79 )
    2059.0 ( 4987.97 )
        CD5+CD19+, 3M FU (n=92, 53)
    121.1 ( 5479.03 )
    2143.9 ( 4280.66 )
        CD5+CD19+, 6M FU (n=89, 48)
    1968.3 ( 15975.52 )
    2363.5 ( 4937.00 )
        CD5+CD19+, 9M FU (n=82, 41)
    1411.3 ( 6965.41 )
    4008.5 ( 13550.03 )
        CD5+CD19+, 12M FU (n=74, 35)
    2198.5 ( 10743.58 )
    2316.0 ( 8763.12 )
        CD5+CD19+, 15M FU (n=57, 30)
    -84.4 ( 4140.77 )
    1246.2 ( 2894.20 )
        CD5+CD19+, 18M FU (n=48, 27)
    1844.1 ( 10091.28 )
    1250.9 ( 3182.14 )
        CD5+CD19+, 21M FU (n=42, 24)
    -395.1 ( 4521.30 )
    1147.5 ( 2191.69 )
        CD5+CD19+, 24M FU (n=38, 24)
    279.4 ( 6250.23 )
    2354.0 ( 6726.31 )
        CD5+CD19+, 27M FU (n=34, 20)
    -368.6 ( 4829.16 )
    2250.8 ( 5833.72 )
        CD5+CD19+, 30M FU (n=27, 16)
    -354.4 ( 5686.14 )
    2189.3 ( 6246.05 )
        CD5+CD19+, 33M FU (n=23, 14)
    -397.0 ( 2767.27 )
    3024.8 ( 7543.26 )
        CD5+CD19+, 36M FU (n=23, 13)
    -354.8 ( 2767.77 )
    3668.4 ( 8581.98 )
        CD5+CD19+, 39M FU (n=19, 10)
    -163.7 ( 3116.92 )
    1217.1 ( 2441.59 )
        CD5+CD19+, 42M FU (n=16, 9)
    -81.7 ( 3426.53 )
    2005.9 ( 4327.53 )
        CD5+CD19+, 45M FU (n=13, 7)
    466.9 ( 919.60 )
    450.4 ( 1031.86 )
        CD5+CD19+, 48M FU (n=10, 5)
    1255.3 ( 2289.34 )
    643.4 ( 1270.16 )
        CD5+CD19+, 51M FU (n=5, 4)
    4341.4 ( 8803.05 )
    1104.8 ( 2004.49 )
        CD5+CD19+, 54M FU (n=5, 2)
    1689.8 ( 2357.27 )
    237.5 ( 251.02 )
        CD5+CD19+, 57M FU (n=3, 2)
    703.3 ( 898.82 )
    186.0 ( 145.66 )
        CD5+CD19+, 60M FU (n=2, 2)
    237.0 ( 326.68 )
    278.5 ( 392.44 )
        CD5+CD19+, withdrawal (n=73, 83)
    8916.4 ( 25922.35 )
    13991.9 ( 23553.42 )
        CD5-CD19+, C2 W9, M3 (n=192, 166)
    -17.9 ( 588.42 )
    81.1 ( 781.76 )
        CD5-CD19+, C3 W17, M5 (n=185, 169)
    5.2 ( 358.12 )
    50.7 ( 168.87 )
        CD5-CD19+, C4 W25, M7 (n=170, 152)
    73.9 ( 687.62 )
    228.2 ( 2037.16 )
        CD5-CD19+, C5 W33, M9 (168, 147)
    87.5 ( 971.22 )
    98.9 ( 401.27 )
        CD5-CD19+, C6 W41, M11 (n=154, 129)
    -13.1 ( 257.81 )
    92.7 ( 296.23 )
        CD5-CD19+, C7 W49, M13 (n=152, 122)
    5.3 ( 368.66 )
    77.5 ( 125.81 )
        CD5-CD19+, C8 W57, M15 (n=137, 108)
    -13.3 ( 279.89 )
    95.9 ( 143.95 )
        CD5-CD19+, C9 W65, M17 (n=123, 90)
    -4.4 ( 349.91 )
    128.3 ( 294.11 )
        CD5-CD19+, C10 W73, M19 (n=120, 89)
    3.3 ( 421.97 )
    172.5 ( 555.27 )
        CD5-CD19+, C11 W81, M21 (n=112, 89)
    -20.7 ( 303.21 )
    127.2 ( 150.18 )
        CD5-CD19+, C12 W89, M23 (n= 110, 74)
    -13.5 ( 306.57 )
    143.7 ( 251.88 )
        CD5-CD19+, C13 W97, M25 (100, 64)
    7.9 ( 103.85 )
    184.0 ( 403.97 )
        CD5-CD19+, 3M FU (n=92, 53)
    27.4 ( 522.67 )
    145.7 ( 229.93 )
        CD5-CD19+, 6M FU (n=89, 48)
    22.6 ( 428.70 )
    153.8 ( 330.63 )
        CD5-CD19+, 9M FU (n=82, 41)
    13.2 ( 368.63 )
    140.9 ( 107.92 )
        CD5-CD19+, 12M FU (n=74, 35)
    86.4 ( 769.73 )
    147.2 ( 136.93 )
        CD5-CD19+, 15M FU (n=57, 30)
    10.8 ( 393.47 )
    154.8 ( 120.86 )
        CD5-CD19+, 18M FU (n=48, 27)
    84.7 ( 146.38 )
    173.5 ( 142.95 )
        CD5-CD19+, 21M FU (n=42, 24)
    16.2 ( 450.95 )
    175.9 ( 158.31 )
        CD5-CD19+, 24M FU (n=38, 24)
    574.7 ( 2993.58 )
    223.2 ( 200.06 )
        CD5-CD19+, 27M FU (n=34, 20)
    102.0 ( 643.44 )
    153.3 ( 110.37 )
        CD5-CD19+, 30M FU (n=27, 16)
    38.7 ( 271.84 )
    142.9 ( 106.57 )
        CD5-CD19+, 33M FU (n=23, 14)
    98.3 ( 117.18 )
    157.5 ( 96.69 )
        CD5-CD19+, 36M FU (n=23, 13)
    141.1 ( 179.33 )
    215.2 ( 298.90 )
        CD5-CD19+, 39M FU (n=19, 10)
    134.3 ( 167.33 )
    183.9 ( 249.78 )
        CD5-CD19+, 42M FU (n=16, 9)
    113.3 ( 131.48 )
    361.1 ( 601.36 )
        CD5-CD19+, 45M FU (n=13, 7)
    108.6 ( 140.97 )
    157.7 ( 116.04 )
        CD5-CD19+, 48M FU (n=10, 5)
    147.7 ( 185.10 )
    180.6 ( 175.93 )
        CD5-CD19+, 51M FU (n=5, 4)
    162.6 ( 229.87 )
    139.3 ( 82.75 )
        CD5-CD19+, 54M FU (n=5, 2)
    221.2 ( 217.75 )
    315.0 ( 43.84 )
        CD5-CD19+, 57M FU (n=3, 2)
    138.3 ( 196.32 )
    195.5 ( 17.68 )
        CD5-CD19+, 60M FU (n=2, 2)
    180.5 ( 222.74 )
    127.0 ( 173.95 )
        CD5-CD19+, withdrawal (n=73, 83)
    593.5 ( 2028.89 )
    552.7 ( 1799.49 )
    No statistical analyses for this end point

    Secondary: Summary of covariates to compute cox proportional hazards regression model for relationship between investigator assessed progression-free survival and the indicated prognostic markers

    		 Close Top of page
    End point title
    		 Summary of covariates to compute cox proportional hazards regression model for relationship between investigator assessed progression-free survival and the indicated prognostic markers
    End point description
    Blood samples were collected for the assessment of the following prognostic markers at Baseline (BL) and upon relapse: immunoglobulin heavy chain variable region (IgVH) mutational status; VH3-21 usage; Cytogenetics (by fluorescent in situ hybridization [FISH]) including 6q-, 11q-, +12q, 17p-, 13q- deletions; beta 2 microglobulin. Cox-regression model was used to explore the relationship between progression-free survival and the following explanatory variables: treatment group, cytogenetics (analyzed by FISH) at BL, IgVH mutational status at BL, beta 2 microglobulin at BL, BL CD20 and BL complement level. For each covariate, a hazard ratio <1 indicates a lower risk on the first effect tested compared with the other effects tested. Cytogenetics Group (based on >=20%)=CY G.
    End point type
    Secondary
    End point timeframe
    From Baseline until the end of the study (up to 79 months)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    240
    240
    Units: Participants
        CY G: 6q- or +12q or 13q
    36
    12
        CY G: 17p-
    7
    4
        CY G: 11q-
    11
    10
        CY G: no aberration
    166
    181
        CY G: missing
    20
    33
        B2 Microglobulin G 2: > 3500 μg/L
    80
    68
        B2 Microglobulin G 2: <=3500 μg/L
    157
    171
        B2 Microglobulin G 2: missing
    3
    1
        IgVH Mutational Status 1: mutated
    54
    74
        IgVH Mutational Status 1: unmutated
    139
    116
        IgVH Mutational Status 1: not available
    3
    1
        IgVH Mutational Status 1: missing
    44
    49
        VH3-21 Usage Flag: Yes
    7
    7
        VH3-21 Usage Flag: No
    233
    233
    Statistical analysis title
    		 Cox proportional hazards regression model
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.547
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.051
         upper limit
    		 2.276
    Statistical analysis title
    		 Cox proportional hazards regression model
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    9.303
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.934
         upper limit
    		 17.54
    Statistical analysis title
    		 Cox proportional hazards regression model
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    4.219
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.468
         upper limit
    		 7.21
    Statistical analysis title
    		 Cox proportional hazards regression model
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.832
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.434
         upper limit
    		 2.339
    Statistical analysis title
    		 Cox proportional hazards regression model
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.573
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.432
         upper limit
    		 0.76
    Statistical analysis title
    		 Cox proportional hazards regression model
    Comparison groups
    Ofatumumab v Observation
    Number of subjects included in analysis
    480
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.301
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.692
         upper limit
    		 2.448

    Secondary: Cmax and Ctrough of ofatumumab

    		 Close Top of page
    End point title
    		 Cmax and Ctrough of ofatumumab
    End point description
    Blood samples were collected to assess the plasma concentration of ofatumumab. Maximum concentration (Cmax) and observed drug concentration prior to the next dose (Ctrough) were determined. Blood samples were collected at pre-dose and 0.5 hours after the end of the infusion at treatment on Month 1 Week 1 (Day 1), Month 1 Week 2 (Day 8), and at every second infusion.
    End point type
    Secondary
    End point timeframe
    Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    221
    0 [25]
    Units: micrograms per milliliter (µg/mL)
    geometric mean (geometric coefficient of variation)
        Cmax, Cycle 1 Week 1
    73.8 ( 65 )
    ( )
        Cmax, Cycle 1 Week 2
    264 ( 50 )
    ( )
        Cmax, Cycle 4
    275 ( 31 )
    ( )
        Ctrough, Cycle 1 Week 2
    16.3 ( 254 )
    ( )
        Ctrough, Cycle 4
    9.9 ( 1323 )
    ( )
    Notes
    [25] - analysis not done for this group
    No statistical analyses for this end point

    Secondary: Total plasma clearance (CL) of ofatumumab

    		 Close Top of page
    End point title
    		 Total plasma clearance (CL) of ofatumumab
    End point description
    Plasma clearance is defined as the plasma volume that is cleared of drug per unit of time.
    End point type
    Secondary
    End point timeframe
    Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    190
    0 [26]
    Units: millileters per hour (mL/hour)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1
    49.1 ( 38 )
    ( )
        Cycle 1 Week 2
    9.6 ( 43 )
    ( )
        Cycle 4
    8.1 ( 50 )
    ( )
    Notes
    [26] - analysis not done for this group.
    No statistical analyses for this end point

    Secondary: AUC(0-tau) of ofatumumab

    		 Close Top of page
    End point title
    		 AUC(0-tau) of ofatumumab
    End point description
    Area under the concentration time curve over the dosing interval (AUC[0-tau]) is a measure of the drug exposure over time.
    End point type
    Secondary
    End point timeframe
    Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    190
    0 [27]
    Units: micrograms*hour per mL (µg*hour/mL)
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1
    6113 ( 38 )
    ( )
        Cycle 1 Week 2
    104013 ( 43 )
    ( )
        Cycle 4
    122782 ( 50 )
    ( )
    Notes
    [27] - analysis not done for this group.
    No statistical analyses for this end point

    Secondary: Vss of ofatumumab

    		 Close Top of page
    End point title
    		 Vss of ofatumumab
    End point description
    Volume of distribution at steady state (Vss) is defined as the apparent volume of distribution of a drug between plasma and the rest of the body at steady state. Data from all time points collected were used to calculate one Vss value for each individual.
    End point type
    Secondary
    End point timeframe
    Day 1 Month 1 ( Cycle 1) through Month 7 ( Cycle 4)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    224
    0 [28]
    Units: Liters (L)
        geometric mean (geometric coefficient of variation)
    6.0 ( 27 )
    ( )
    Notes
    [28] - analysis not done for this group.
    No statistical analyses for this end point

    Secondary: Plasma half-life (t1/2) of ofatumumab

    		 Close Top of page
    End point title
    		 Plasma half-life (t1/2) of ofatumumab
    End point description
    The terminal half life (t1/2) of ofatumumab is defined as the time required for the plasma concentration of ofatumumab to reach half of its original value.
    End point type
    Secondary
    End point timeframe
    Day 1 of Month 1 (Cycle 1 Week 1); Day 8 of Month 1 (Cycle 1 Week 2); and Month 7 (Cycle 4)
    End point values
    		 Ofatumumab Observation
    Number of subjects analysed
    190
    0 [29]
    Units: hours
    geometric mean (geometric coefficient of variation)
        Cycle 1 Week 1
    126 ( 35 )
    ( )
        Cycle 1 Week 2
    458 ( 36 )
    ( )
        Cycle 4
    542 ( 48 )
    ( )
    Notes
    [29] - analysis not done for this group.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study medication until 60 days after the last dose of study medication or until the last observation at Visit 14 for AEs (up to 26 months) and until end of study for SAEs (88 months).
    Adverse event reporting additional description
    All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 88 months.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Ofatumumab
    Reporting group description
    		 Ofatumumab Participants with relapsed CLL received IV infusions of ofatumumab on Day 1 (300 mg) and Day 8 (1000 mg) in the first cycle, followed by infusions of 1000 mg every 2 months for up to 2 years following the first 1000 mg dose.

    Reporting group title
    Observation
    Reporting group description
    		 Participants with relapsed CLL received no treatment and were under observation for up to 2 years.

    Reporting group title
    Total
    Reporting group description
    		 All Patients

    Serious adverse events
    		 Ofatumumab Observation Total
    Total subjects affected by serious adverse events
         subjects affected / exposed
    120 / 239 (50.21%)
    120 / 241 (49.79%)
    240 / 480 (50.00%)
         number of deaths (all causes)
    88
    87
    175
         number of deaths resulting from adverse events
    1
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma gastric
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaplastic large cell lymphoma T- and null-cell types
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    2 / 239 (0.84%)
    1 / 241 (0.41%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Brain neoplasm malignant
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diffuse large B-cell lymphoma
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Endometrial adenocarcinoma
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Extraskeletal myxoid chondrosarcoma
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal carcinoma
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hodgkin's disease
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma metastatic
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    2 / 239 (0.84%)
    1 / 241 (0.41%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Metastases to central nervous system
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastatic squamous cell carcinoma
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Myelodysplastic syndrome
         subjects affected / exposed
    2 / 239 (0.84%)
    2 / 241 (0.83%)
    4 / 480 (0.83%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
    1 / 5
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    Neoplasm malignant
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine carcinoma of the skin
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Prostate cancer
         subjects affected / exposed
    1 / 239 (0.42%)
    2 / 241 (0.83%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Rectal cancer
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Refractory anaemia with an excess of blasts
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal neoplasm
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Richter's syndrome
         subjects affected / exposed
    0 / 239 (0.00%)
    2 / 241 (0.83%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin cancer
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Spinal meningioma benign
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    3 / 239 (1.26%)
    1 / 241 (0.41%)
    4 / 480 (0.83%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    T-cell lymphoma
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tongue neoplasm malignant stage unspecified
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic stenosis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    2 / 239 (0.84%)
    1 / 241 (0.41%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery aneurysm
         subjects affected / exposed
    2 / 239 (0.84%)
    1 / 241 (0.41%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Venoocclusive disease
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Allogenic bone marrow transplantation therapy
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cataract operation
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mastectomy
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nasal septal operation
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 239 (0.00%)
    2 / 241 (0.83%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Condition aggravated
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    4 / 239 (1.67%)
    3 / 241 (1.24%)
    7 / 480 (1.46%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
    Malaise
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    19 / 239 (7.95%)
    18 / 241 (7.47%)
    37 / 480 (7.71%)
         occurrences causally related to treatment / all
    3 / 31
    0 / 20
    3 / 51
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Immune system disorders
    Acute graft versus host disease
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Acute graft versus host disease in skin
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Allergy to arthropod bite
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Allergy to immunoglobulin therapy
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Graft versus host disease in gastrointestinal tract
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Alveolitis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asphyxia
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Bronchiectasis
         subjects affected / exposed
    2 / 239 (0.84%)
    1 / 241 (0.41%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 239 (0.42%)
    2 / 241 (0.83%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 239 (0.84%)
    4 / 241 (1.66%)
    6 / 480 (1.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Epistaxis
         subjects affected / exposed
    2 / 239 (0.84%)
    2 / 241 (0.83%)
    4 / 480 (0.83%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hiccups
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 239 (0.00%)
    2 / 241 (0.83%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Interstitial lung disease
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 239 (0.42%)
    2 / 241 (0.83%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary alveolar haemorrhage
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Pulmonary embolism
         subjects affected / exposed
    2 / 239 (0.84%)
    2 / 241 (0.83%)
    4 / 480 (0.83%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Respiratory disorder
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 239 (0.00%)
    2 / 241 (0.83%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Psychiatric disorders
    Aggression
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychomotor retardation
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthroscopy
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calcium ionised increased
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Capillary permeability increased
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Heart rate irregular
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Allergic transfusion reaction
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dislocation of vertebra
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Face injury
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 239 (0.42%)
    2 / 241 (0.83%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 239 (0.42%)
    2 / 241 (0.83%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 239 (0.42%)
    2 / 241 (0.83%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscle strain
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    3 / 239 (1.26%)
    3 / 241 (1.24%)
    6 / 480 (1.25%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
    Upper limb fracture
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound secretion
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 239 (0.84%)
    2 / 241 (0.83%)
    4 / 480 (0.83%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 239 (0.42%)
    2 / 241 (0.83%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    Cardiac failure
         subjects affected / exposed
    3 / 239 (1.26%)
    2 / 241 (0.83%)
    5 / 480 (1.04%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
    0 / 10
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
    Cardiac failure acute
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 239 (0.42%)
    3 / 241 (1.24%)
    4 / 480 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    Myocardial ischaemia
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Carotid artery stenosis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Cerebrovascular accident
         subjects affected / exposed
    0 / 239 (0.00%)
    2 / 241 (0.83%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Depressed level of consciousness
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paraparesis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxic neuropathy
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Agranulocytosis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    5 / 239 (2.09%)
    7 / 241 (2.90%)
    12 / 480 (2.50%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 7
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    1 / 239 (0.42%)
    2 / 241 (0.83%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    18 / 239 (7.53%)
    10 / 241 (4.15%)
    28 / 480 (5.83%)
         occurrences causally related to treatment / all
    6 / 21
    0 / 11
    6 / 32
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    2 / 239 (0.84%)
    1 / 241 (0.41%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune thrombocytopenic purpura
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    5 / 239 (2.09%)
    5 / 241 (2.07%)
    10 / 480 (2.08%)
         occurrences causally related to treatment / all
    6 / 7
    0 / 5
    6 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Splenic infarction
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 239 (0.42%)
    3 / 241 (1.24%)
    4 / 480 (0.83%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenic purpura
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Colitis
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 239 (0.00%)
    2 / 241 (0.83%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eosinophilic colitis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal infarction
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Intestinal obstruction
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal spasm
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Small intestinal perforation
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Hepatic failure
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Hepatotoxicity
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Blister
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erythema multiforme
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin lesion
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 239 (0.00%)
    2 / 241 (0.83%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 239 (0.42%)
    2 / 241 (0.83%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoporotic fracture
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute sinusitis
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspergillus infection
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial disease carrier
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blastocystis infection
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    4 / 239 (1.67%)
    3 / 241 (1.24%)
    7 / 480 (1.46%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 3
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    1 / 239 (0.42%)
    5 / 241 (2.07%)
    6 / 480 (1.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Campylobacter colitis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Campylobacter gastroenteritis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 239 (0.84%)
    5 / 241 (2.07%)
    7 / 480 (1.46%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic sinusitis
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus viraemia
         subjects affected / exposed
    0 / 239 (0.00%)
    2 / 241 (0.83%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocarditis enterococcal
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterobacter bacteraemia
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterobacter sepsis
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterococcal sepsis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis viral
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epiglottitis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal fungal infection
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Genital herpes
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes simplex
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes virus infection
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    3 / 239 (1.26%)
    4 / 241 (1.66%)
    7 / 480 (1.46%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 4
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster disseminated
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster oticus
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    4 / 239 (1.67%)
    1 / 241 (0.41%)
    5 / 480 (1.04%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    1 / 239 (0.42%)
    2 / 241 (0.83%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    JC virus infection
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Klebsiella bacteraemia
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leishmaniasis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Listeria sepsis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Listeriosis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 8
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    5 / 239 (2.09%)
    3 / 241 (1.24%)
    8 / 480 (1.67%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 4
    1 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Meningitis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis bacterial
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis pneumococcal
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mucormycosis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mycobacterial infection
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuroborreliosis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Nocardiosis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parvovirus infection
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periorbital cellulitis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Perirectal abscess
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal bacteraemia
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal sepsis
         subjects affected / exposed
    0 / 239 (0.00%)
    2 / 241 (0.83%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    2 / 239 (0.84%)
    1 / 241 (0.41%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    37 / 239 (15.48%)
    35 / 241 (14.52%)
    72 / 480 (15.00%)
         occurrences causally related to treatment / all
    14 / 49
    0 / 54
    14 / 103
         deaths causally related to treatment / all
    0 / 5
    0 / 6
    0 / 11
    Pneumonia bacterial
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pseudomonal
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Pneumonia streptococcal
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Post procedural cellulitis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural pneumonia
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Post procedural sepsis
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative abscess
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Progressive multifocal leukoencephalopathy
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Pseudomonas infection
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    2 / 239 (0.84%)
    0 / 241 (0.00%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Respiratory tract infection
         subjects affected / exposed
    4 / 239 (1.67%)
    4 / 241 (1.66%)
    8 / 480 (1.67%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    Sepsis
         subjects affected / exposed
    8 / 239 (3.35%)
    5 / 241 (2.07%)
    13 / 480 (2.71%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 5
    1 / 14
         deaths causally related to treatment / all
    0 / 5
    0 / 1
    0 / 6
    Septic shock
         subjects affected / exposed
    5 / 239 (2.09%)
    3 / 241 (1.24%)
    8 / 480 (1.67%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
    0 / 8
         deaths causally related to treatment / all
    0 / 4
    0 / 3
    0 / 7
    Sinusitis
         subjects affected / exposed
    3 / 239 (1.26%)
    2 / 241 (0.83%)
    5 / 480 (1.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Staphylococcal infection
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 239 (1.67%)
    2 / 241 (0.83%)
    6 / 480 (1.25%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 2
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 239 (1.26%)
    5 / 241 (2.07%)
    8 / 480 (1.67%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 5
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Varicella
         subjects affected / exposed
    1 / 239 (0.42%)
    1 / 241 (0.41%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Varicella zoster virus infection
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 239 (0.42%)
    2 / 241 (0.83%)
    3 / 480 (0.63%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glucose tolerance impaired
         subjects affected / exposed
    1 / 239 (0.42%)
    0 / 241 (0.00%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 239 (0.00%)
    2 / 241 (0.83%)
    2 / 480 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypermetabolism
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 239 (0.00%)
    1 / 241 (0.41%)
    1 / 480 (0.21%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ofatumumab Observation Total
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    202 / 239 (84.52%)
    139 / 241 (57.68%)
    341 / 480 (71.04%)
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    42 / 239 (17.57%)
    0 / 241 (0.00%)
    42 / 480 (8.75%)
         occurrences all number
    67
    0
    67
    Nervous system disorders
    Headache
         subjects affected / exposed
    23 / 239 (9.62%)
    7 / 241 (2.90%)
    30 / 480 (6.25%)
         occurrences all number
    28
    9
    37
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    61 / 239 (25.52%)
    22 / 241 (9.13%)
    83 / 480 (17.29%)
         occurrences all number
    105
    24
    129
    Thrombocytopenia
         subjects affected / exposed
    13 / 239 (5.44%)
    11 / 241 (4.56%)
    24 / 480 (5.00%)
         occurrences all number
    15
    11
    26
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    33 / 239 (13.81%)
    22 / 241 (9.13%)
    55 / 480 (11.46%)
         occurrences all number
    36
    22
    58
    Oedema peripheral
         subjects affected / exposed
    12 / 239 (5.02%)
    10 / 241 (4.15%)
    22 / 480 (4.58%)
         occurrences all number
    14
    10
    24
    Pyrexia
         subjects affected / exposed
    41 / 239 (17.15%)
    23 / 241 (9.54%)
    64 / 480 (13.33%)
         occurrences all number
    56
    27
    83
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    12 / 239 (5.02%)
    2 / 241 (0.83%)
    14 / 480 (2.92%)
         occurrences all number
    12
    2
    14
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    13 / 239 (5.44%)
    11 / 241 (4.56%)
    24 / 480 (5.00%)
         occurrences all number
    14
    11
    25
    Diarrhoea
         subjects affected / exposed
    41 / 239 (17.15%)
    13 / 241 (5.39%)
    54 / 480 (11.25%)
         occurrences all number
    47
    14
    61
    Nausea
         subjects affected / exposed
    13 / 239 (5.44%)
    8 / 241 (3.32%)
    21 / 480 (4.38%)
         occurrences all number
    15
    8
    23
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    58 / 239 (24.27%)
    28 / 241 (11.62%)
    86 / 480 (17.92%)
         occurrences all number
    71
    37
    108
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    23 / 239 (9.62%)
    9 / 241 (3.73%)
    32 / 480 (6.67%)
         occurrences all number
    29
    10
    39
    Rash
         subjects affected / exposed
    26 / 239 (10.88%)
    10 / 241 (4.15%)
    36 / 480 (7.50%)
         occurrences all number
    27
    10
    37
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    14 / 239 (5.86%)
    6 / 241 (2.49%)
    20 / 480 (4.17%)
         occurrences all number
    17
    7
    24
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    20 / 239 (8.37%)
    12 / 241 (4.98%)
    32 / 480 (6.67%)
         occurrences all number
    23
    14
    37
    Back pain
         subjects affected / exposed
    15 / 239 (6.28%)
    12 / 241 (4.98%)
    27 / 480 (5.63%)
         occurrences all number
    16
    12
    28
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    21 / 239 (8.79%)
    17 / 241 (7.05%)
    38 / 480 (7.92%)
         occurrences all number
    28
    23
    51
    Herpes zoster
         subjects affected / exposed
    14 / 239 (5.86%)
    8 / 241 (3.32%)
    22 / 480 (4.58%)
         occurrences all number
    16
    8
    24
    Influenza
         subjects affected / exposed
    16 / 239 (6.69%)
    10 / 241 (4.15%)
    26 / 480 (5.42%)
         occurrences all number
    18
    12
    30
    Nasopharyngitis
         subjects affected / exposed
    22 / 239 (9.21%)
    22 / 241 (9.13%)
    44 / 480 (9.17%)
         occurrences all number
    27
    29
    56
    Pneumonia
         subjects affected / exposed
    17 / 239 (7.11%)
    11 / 241 (4.56%)
    28 / 480 (5.83%)
         occurrences all number
    28
    11
    39
    Respiratory tract infection
         subjects affected / exposed
    17 / 239 (7.11%)
    15 / 241 (6.22%)
    32 / 480 (6.67%)
         occurrences all number
    19
    18
    37
    Rhinitis
         subjects affected / exposed
    14 / 239 (5.86%)
    4 / 241 (1.66%)
    18 / 480 (3.75%)
         occurrences all number
    15
    4
    19
    Sinusitis
         subjects affected / exposed
    22 / 239 (9.21%)
    9 / 241 (3.73%)
    31 / 480 (6.46%)
         occurrences all number
    25
    11
    36
    Upper respiratory tract infection
         subjects affected / exposed
    52 / 239 (21.76%)
    26 / 241 (10.79%)
    78 / 480 (16.25%)
         occurrences all number
    75
    40
    115

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Nov 2009
    Addition of baseline MRD, exploratory endpoints, post-PD PRO and clarifications.
    21 May 2010
    Added study name and clarifications, modified I/E
    07 Feb 2013
    At the request of the French regulatory agency related information from the Study Procedures Manual (SPM) was added into Section 6.4.6
    17 Dec 2013
    FDA request for additional HBV information and protocol clarifications
    26 Aug 2014
    As the significance level was met at the interim analysis of efficacy, further enrollment in the study was discontinued.
    01 Apr 2016
    References to GlaxoSmithKline or its staff were replaced with that of Novartis and its authorized agents to align with the change of sponsorship

    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.
    Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.
    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-Fri Apr 26 09:32:50 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA