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    Clinical Trial Results:
    A randomized, double-blind, parallel group, placebo-controlled, multi-center study to assess the safety and tolerability of monthly subcutaneous administrations of a low and high dose cohort of osocimab to ESRD patients on regular hemodialysis

    Summary
    EudraCT number
    		 2019-003957-27
    Trial protocol
    		 CZ   AT   GR   BE   PT   NL   LT   PL   HU   BG   IT  
    Global end of trial date
    30 May 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 May 2023
    First version publication date
    21 May 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    BAY1213790/20115
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04523220
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser Wilhelm Allee, Leverkusen, Germany, D-51368
    Public contact
    Therapeutic Area Head, Bayer AG, +49 30 300139003, clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG, +49 30 300139003, clinical-trials-contact@bayer.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
    27 Jun 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 May 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to clinically assess the safety and tolerability of different doses of osocimab administered subcutaneously once a month during main treatment period as compared to placebo.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and the International Council for Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent was read by and explained to all the subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Aug 2020
    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
    Austria: 10
    Country: Number of subjects enrolled
    Lithuania: 5
    Country: Number of subjects enrolled
    Poland: 27
    Country: Number of subjects enrolled
    Australia: 6
    Country: Number of subjects enrolled
    Israel: 28
    Country: Number of subjects enrolled
    Japan: 60
    Country: Number of subjects enrolled
    United States: 114
    Country: Number of subjects enrolled
    Czechia: 15
    Country: Number of subjects enrolled
    Greece: 25
    Country: Number of subjects enrolled
    Italy: 20
    Country: Number of subjects enrolled
    Bulgaria: 40
    Country: Number of subjects enrolled
    Netherlands: 13
    Country: Number of subjects enrolled
    Spain: 17
    Country: Number of subjects enrolled
    Belgium: 23
    Country: Number of subjects enrolled
    Hungary: 50
    Country: Number of subjects enrolled
    Portugal: 30
    Country: Number of subjects enrolled
    Russian Federation: 110
    Country: Number of subjects enrolled
    Turkey: 20
    Country: Number of subjects enrolled
    Ukraine: 91
    Worldwide total number of subjects
    704
    EEA total number of subjects
    275
    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)
    418
    From 65 to 84 years
    271
    85 years and over
    15

    Subject disposition

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    Recruitment
    Recruitment details
    		 Study was conducted at multiple centers in 19 countries/regions, between 28-Aug-2020 (first subject first visit) and 30-May-2022 (last subject last visit).

    Pre-assignment
    Screening details
    		 A total of 859 subjects were screened; 155 subjects were not randomized. Most common reasons for not being randomized was screen failure (144 subjects). 704 subjects were randomized to treatment; 18 subjects did not receive treatment. The remaining 686 subjects were treated.

    Period 1
    Period 1 title
    Main treatment Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Higher-dose osocimab
    Arm description
    		 Subjects were randomized to receive Osocimab (BAY1213790) 210 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 105 mg for 6 months in main treatment phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osocimab
    Investigational medicinal product code
    BAY1213790
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subcutaneous abdominal injection; starting with 1 loading dose of 210 mg, followed by monthly maintenance doses of 105 mg until the end of the main treatment period for 6 months.

    Arm title
    		 Lower-dose osocimab
    Arm description
    		 Subjects were randomized to receive Osocimab (BAY1213790) 105 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 52.5 mg for 6 months in main treatment phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osocimab
    Investigational medicinal product code
    BAY1213790
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subcutaneous abdominal injection; starting with 1 loading dose of 105 mg, followed by monthly maintenance doses of 52.5 mg until the end of the main treatment period for 6 months.

    Arm title
    		 Placebo
    Arm description
    		 Subjects were randomized to receive matching placebo subcutaneously in the same manner as Osocimab until the end of the main treatment period for 6 months.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Matching placebo, subcutaneous abdominal injection; starting with 1 loading dose, followed by monthly maintenance doses in the same manner as Osocimab until the end of the main treatment period for 6 months.

    Number of subjects in period 1
    		Higher-dose osocimab Lower-dose osocimab Placebo
    Started
    234
    235
    235
    Treated
    224
    232
    230
    Completed
    194
    199
    206
    Not completed
    40
    36
    29
         Consent withdrawn by subject
    3
    3
    4
         Physician decision
    1
    1
    -
         Subject Decision
    5
    7
    3
         Study drug never adminstered
    10
    3
    5
         Adverse event, non-fatal
    11
    9
    9
         Other
    5
    2
    4
         Death
    5
    11
    4
    Period 2
    Period 2 title
    Extension treatment period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Higher-dose osocimab
    Arm description
    		 Subjects received Osocimab (BAY1213790) at monthly maintenance doses of 105 mg up to a maximum of 12 months or until the last subject randomized to the study has performed the end of main treatment (EOMT) visit (whichever comes first) in extension treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osocimab
    Investigational medicinal product code
    BAY1213790
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subcutaneous abdominal injection; monthly maintenance doses of 105 mg until the end of the extension treatment period.

    Arm title
    		 Lower-dose osocimab
    Arm description
    		 Subjects received Osocimab (BAY1213790) at monthly maintenance doses of 52.5 mg up to a maximum of 12 months or until the last subject randomized to the study has performed the end of main treatment (EOMT) visit (whichever comes first) in extension treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Osocimab
    Investigational medicinal product code
    BAY1213790
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subcutaneous abdominal injection; monthly maintenance doses of 52.5 mg until the end of the extension treatment period.

    Arm title
    		 Placebo
    Arm description
    		 Subjects received matching placebo subcutaneously in the same manner as Osocimab in extension treatment period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Matching placebo, subcutaneous abdominal injection; monthly maintenance doses in the same manner as Osocimab until the end of the extension treatment period.

    Number of subjects in period 2
    		Higher-dose osocimab Lower-dose osocimab Placebo
    Started
    194
    199
    206
    Completed
    174
    178
    176
    Not completed
    20
    21
    30
         Physician decision
    1
    -
    3
         Consent withdrawn by subject
    -
    1
    1
         Subject Decision
    5
    2
    4
         Adverse event, non-fatal
    6
    7
    9
         Other
    2
    6
    6
         Death
    6
    4
    7
         Study drug never administered
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Higher-dose osocimab
    Reporting group description
    		 Subjects were randomized to receive Osocimab (BAY1213790) 210 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 105 mg for 6 months in main treatment phase.

    Reporting group title
    Lower-dose osocimab
    Reporting group description
    		 Subjects were randomized to receive Osocimab (BAY1213790) 105 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 52.5 mg for 6 months in main treatment phase.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects were randomized to receive matching placebo subcutaneously in the same manner as Osocimab until the end of the main treatment period for 6 months.

    Reporting group values
    		 Higher-dose osocimab Lower-dose osocimab Placebo Total
    Number of subjects
    		 234 235 235 704
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        median (standard deviation)
    		 61.0 ( 13.4 ) 61.1 ( 12.9 ) 59.5 ( 13.3 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 85 90 81 256
        Male
    		 149 145 154 448
    Race
    Units: Subjects
        WHITE
    		 193 194 190 577
        BLACK OR AFRICAN AMERICAN
    		 19 18 22 59
        ASIAN
    		 21 21 21 63
        AMERICAN INDIAN OR ALASKA NATIVE
    		 1 0 1 2
        NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER
    		 0 1 1 2
        MULTIPLE
    		 0 1 0 1
    Activated partial thromboplastin time (aPTT) value at baseline
    aPTT was measured via the kaolin-trigger method (clotting assay). Furthermore, the aPTT assay was conducted after in vitro- neutralization of heparin in order to separate potential heparin effects from the PD effect of osocimab.The actual number of subjects entering the analysis was 628 (Higher-dose osocimab 209 subjects; Lower-dose osocimab 213 subjects; Placebo 206 subjects).
    Units: seconds
        geometric mean (standard deviation)
    		 31.49 ( 1.10 ) 31.32 ( 1.10 ) 31.65 ( 1.09 ) -
    Factor XI (FXI) activity at baseline
    Factor XI activity was assessed with an aPTT-based coagulation test using FXI deficient plasma. Furthermore, the assay was conducted after in vitro-neutralization of heparin in order to separate potential heparin effects from the PD effect of osocimab. The actual number of subjects entering the analysis was 622 (Higher-dose osocimab 208 subjects; Lower-dose osocimab 212 subjects; Placebo 202 subjects).
    Units: percent
        geometric mean (standard deviation)
    		 100.54 ( 1.29 ) 102.27 ( 1.28 ) 103.09 ( 1.25 ) -

    End points

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    End points reporting groups
    Reporting group title
    Higher-dose osocimab
    Reporting group description
    		 Subjects were randomized to receive Osocimab (BAY1213790) 210 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 105 mg for 6 months in main treatment phase.

    Reporting group title
    Lower-dose osocimab
    Reporting group description
    		 Subjects were randomized to receive Osocimab (BAY1213790) 105 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 52.5 mg for 6 months in main treatment phase.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects were randomized to receive matching placebo subcutaneously in the same manner as Osocimab until the end of the main treatment period for 6 months.
    Reporting group title
    Higher-dose osocimab
    Reporting group description
    		 Subjects received Osocimab (BAY1213790) at monthly maintenance doses of 105 mg up to a maximum of 12 months or until the last subject randomized to the study has performed the end of main treatment (EOMT) visit (whichever comes first) in extension treatment period.

    Reporting group title
    Lower-dose osocimab
    Reporting group description
    		 Subjects received Osocimab (BAY1213790) at monthly maintenance doses of 52.5 mg up to a maximum of 12 months or until the last subject randomized to the study has performed the end of main treatment (EOMT) visit (whichever comes first) in extension treatment period.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received matching placebo subcutaneously in the same manner as Osocimab in extension treatment period.

    Subject analysis set title
    Full analysis set (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects randomly assigned to study intervention.

    Subject analysis set title
    Safety Analysis Set (SAF)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects randomly assigned to study intervention who took at least 1 dose of study intervention. Subjects were analyzed according to the intervention they actually received.

    Subject analysis set title
    Pharmacodynamic analysis set (PDS)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All subjects with at least 1 PD sample in accordance with the PD sampling schedule and without deviation from the protocol that would have interfered with the evaluation of the PD data were included in the PD analysis.

    Primary: Composite of major bleeding (MB) and clinically-relevant non-major bleeding (CRNMB) events as assessed by blinded Central Independent Adjudication Committee (CIAC)

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    End point title
    		 Composite of major bleeding (MB) and clinically-relevant non-major bleeding (CRNMB) events as assessed by blinded Central Independent Adjudication Committee (CIAC)
    End point description
    Descriptive time to composite of treatment emergent major and CRNMB events [in alignment with International Society on Thrombosis and Haemostatsis (ISTH) guidelines] analyses were performed. The cumulative incidence function for the event-of-interest together with the corresponding confidence interval were estimated for each treatment arm using Aalen-Johansen estimators. Cumulative incidence of events up to the day, inclusive.
    End point type
    Primary
    End point timeframe
    From the first dose of study intervention up till 30 days after last study intervention in the main treatment period, up to 6 months
    End point values
    		 Higher-dose osocimab Lower-dose osocimab Placebo
    Number of subjects analysed
    224 [1]
    232 [2]
    230 [3]
    Units: Percentage
        number (confidence interval 90%)
    3.57 (1.91 to 6.04)
    4.32 (2.48 to 6.91)
    6.09 (3.84 to 9.04)
    Notes
    [1] - SAF
    [2] - SAF
    [3] - SAF
    Statistical analysis title
    		 Cause-specific Hazard Ratios
    Statistical analysis description
    Two-sided log-rank tests and Cox proportional hazards model were used in the analyses.
    Comparison groups
    Placebo v Higher-dose osocimab
    Number of subjects included in analysis
    454
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.222
    Method
    		 Logrank
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.59
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.28
         upper limit
    		 1.21
    Statistical analysis title
    		 Cause-specific Hazard Ratios
    Statistical analysis description
    Two-sided log-rank tests and Cox proportional hazards model were used in the analyses.
    Comparison groups
    Lower-dose osocimab v Placebo
    Number of subjects included in analysis
    462
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.427
    Method
    		 Logrank
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.72
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.36
         upper limit
    		 1.42

    Primary: Composite of moderate and severe adverse events (AEs) and serious adverse events (SAEs)

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    End point title
    		 Composite of moderate and severe adverse events (AEs) and serious adverse events (SAEs)
    End point description
    An AE was any untoward medical occurrence in a patient or clinical study subject, whether or not considered related to the study intervention.
    End point type
    Primary
    End point timeframe
    From the first dose of study intervention up until 30 days after last study intervention in the main treatment period, up to 6 months
    End point values
    		 Higher-dose osocimab Lower-dose osocimab Placebo
    Number of subjects analysed
    224 [4]
    232 [5]
    230 [6]
    Units: Percentages
        number (confidence interval 90%)
    38.84 (33.46 to 44.17)
    38.37 (33.10 to 43.60)
    32.17 (27.16 to 37.28)
    Notes
    [4] - SAF
    [5] - SAF
    [6] - SAF
    Statistical analysis title
    		 Cause-specific Hazard Ratios
    Statistical analysis description
    Two-sided log-rank tests and Cox proportional hazards model were used in the analyses.
    Comparison groups
    Lower-dose osocimab v Placebo
    Number of subjects included in analysis
    462
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.166
    Method
    		 Logrank
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.24
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.61
    Statistical analysis title
    		 Cause-specific Hazard Ratios
    Statistical analysis description
    Two-sided log-rank tests and Cox proportional hazards model were used in the analyses.
    Comparison groups
    Higher-dose osocimab v Placebo
    Number of subjects included in analysis
    454
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.128
    Method
    		 Logrank
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.27
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.64

    Secondary: Activated partial thromboplastin time (aPTT) at trough levels

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    End point title
    		 Activated partial thromboplastin time (aPTT) at trough levels
    End point description
    aPTT was measured via the kaolin-trigger method (clotting assay).
    End point type
    Secondary
    End point timeframe
    At baseline and after 6 months (V19 / Day 30)
    End point values
    		 Higher-dose osocimab Lower-dose osocimab Placebo
    Number of subjects analysed
    167 [7]
    174 [8]
    174 [9]
    Units: Ratio
    geometric mean (standard deviation)
        Ratio to Baseline at V19 / Day 30
    1.26 ( 1.11 )
    1.19 ( 1.11 )
    1.02 ( 1.08 )
    Notes
    [7] - PDS
    [8] - PDS
    [9] - PDS
    No statistical analyses for this end point

    Secondary: Factor XI (FXI) activity at trough levels

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    End point title
    		 Factor XI (FXI) activity at trough levels
    End point description
    Factor XI activity was assessed with an aPTT-based coagulation test using FXI deficient plasma.
    End point type
    Secondary
    End point timeframe
    At baseline and after 6 months (V19 / Day 30)
    End point values
    		 Higher-dose osocimab Lower-dose osocimab Placebo
    Number of subjects analysed
    164 [10]
    175 [11]
    171 [12]
    Units: Ratio
    geometric mean (standard deviation)
        Ratio to Baseline at V19 / Day 30
    0.87 ( 1.27 )
    0.94 ( 1.23 )
    0.96 ( 1.20 )
    Notes
    [10] - PDS
    [11] - PDS
    [12] - PDS
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    After the first study dose up until 30 days after last study dose, with up to approx. 19 months. AE reporting for the deaths (all causes) considers all deaths that occurred at any time during the study before the last contact, with up to approx. 23 months
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Higher-dose osocimab
    Reporting group description
    		 Subjects received Osocimab (BAY1213790) 210 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 105 mg

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received matching placebo subcutaneously in the same manner as Osocimab

    Reporting group title
    Lower-dose osocimab
    Reporting group description
    		 Subjects received Osocimab (BAY1213790) 105 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 52.5 mg

    Serious adverse events
    		 Higher-dose osocimab Placebo Lower-dose osocimab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    61 / 224 (27.23%)
    63 / 230 (27.39%)
    67 / 232 (28.88%)
         number of deaths (all causes)
    19
    15
    24
         number of deaths resulting from adverse events
    9
    13
    16
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder neoplasm
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic dissection
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    3 / 224 (1.34%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vena cava thrombosis
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iliac artery dissection
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arterial haemorrhage
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral vein occlusion
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Arteriovenous fistula operation
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip arthroplasty
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parathyroidectomy
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal transplant
         subjects affected / exposed
    5 / 224 (2.23%)
    5 / 230 (2.17%)
    3 / 232 (1.29%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toe amputation
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Central venous catheterisation
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc operation
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dialysis device insertion
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous graft
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder neoplasm surgery
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritoneal catheter insertion
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 224 (0.45%)
    1 / 230 (0.43%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    General physical health deterioration
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Cardiac death
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Reproductive system and breast disorders
    Uterine polyp
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    2 / 224 (0.89%)
    1 / 230 (0.43%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    1 / 224 (0.45%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Angiocardiogram
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous fistula thrombosis
         subjects affected / exposed
    1 / 224 (0.45%)
    3 / 230 (1.30%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shunt occlusion
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous fistula site haemorrhage
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous fistula site complication
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous fistula occlusion
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shunt stenosis
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shunt aneurysm
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular graft thrombosis
         subjects affected / exposed
    1 / 224 (0.45%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Unintentional medical device removal
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular access site inflammation
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    2 / 224 (0.89%)
    2 / 230 (0.87%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Angina pectoris
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    2 / 224 (0.89%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    Cardiac failure chronic
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dressler's syndrome
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 224 (0.00%)
    3 / 230 (1.30%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    2 / 224 (0.89%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery insufficiency
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Mitral valve disease
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute left ventricular failure
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Syncope
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 224 (0.45%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Basal ganglia haemorrhage
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 224 (0.00%)
    2 / 230 (0.87%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Normocytic anaemia
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 224 (0.00%)
    2 / 230 (0.87%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic retinopathy
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal dilatation
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tongue haematoma
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal wall thickening
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrosclerosis
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal haematoma
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Renal cyst ruptured
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal mass
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperparathyroidism secondary
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    4 / 224 (1.79%)
    4 / 230 (1.74%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 224 (0.45%)
    2 / 230 (0.87%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tuberculous pleurisy
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 224 (0.45%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronavirus infection
         subjects affected / exposed
    0 / 224 (0.00%)
    2 / 230 (0.87%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Febrile infection
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Perirectal abscess
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriovenous fistula site infection
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cyst infection
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic foot infection
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atypical mycobacterial infection
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular access site infection
         subjects affected / exposed
    2 / 224 (0.89%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    7 / 224 (3.13%)
    5 / 230 (2.17%)
    8 / 232 (3.45%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    COVID-19 pneumonia
         subjects affected / exposed
    3 / 224 (1.34%)
    8 / 230 (3.48%)
    9 / 232 (3.88%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 8
    0 / 9
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
    Device related bacteraemia
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asymptomatic COVID-19
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 224 (0.45%)
    1 / 230 (0.43%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypervolaemia
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    0 / 224 (0.00%)
    1 / 230 (0.43%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    2 / 232 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic complication
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Ketoacidosis
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    0 / 224 (0.00%)
    0 / 230 (0.00%)
    1 / 232 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    1 / 224 (0.45%)
    0 / 230 (0.00%)
    0 / 232 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         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
    		 Higher-dose osocimab Placebo Lower-dose osocimab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    90 / 224 (40.18%)
    88 / 230 (38.26%)
    85 / 232 (36.64%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    18 / 224 (8.04%)
    16 / 230 (6.96%)
    18 / 232 (7.76%)
         occurrences all number
    20
    17
    24
    Hypotension
         subjects affected / exposed
    15 / 224 (6.70%)
    18 / 230 (7.83%)
    13 / 232 (5.60%)
         occurrences all number
    22
    28
    27
    Nervous system disorders
    Headache
         subjects affected / exposed
    19 / 224 (8.48%)
    14 / 230 (6.09%)
    23 / 232 (9.91%)
         occurrences all number
    21
    15
    26
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    10 / 224 (4.46%)
    12 / 230 (5.22%)
    12 / 232 (5.17%)
         occurrences all number
    10
    13
    12
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    14 / 224 (6.25%)
    14 / 230 (6.09%)
    9 / 232 (3.88%)
         occurrences all number
    15
    17
    12
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    13 / 224 (5.80%)
    16 / 230 (6.96%)
    6 / 232 (2.59%)
         occurrences all number
    16
    18
    6
    Vomiting
         subjects affected / exposed
    7 / 224 (3.13%)
    12 / 230 (5.22%)
    8 / 232 (3.45%)
         occurrences all number
    7
    16
    10
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    12 / 224 (5.36%)
    15 / 230 (6.52%)
    9 / 232 (3.88%)
         occurrences all number
    20
    23
    17
    Infections and infestations
    COVID-19
         subjects affected / exposed
    11 / 224 (4.91%)
    12 / 230 (5.22%)
    14 / 232 (6.03%)
         occurrences all number
    11
    12
    14

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

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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