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    Clinical Trial Results:
    A Placebo-Controlled, Double-Blind, Parallel-Group, Bayesian Adaptive Randomization Design and Dose Regimen-Finding Study With an Open-Label Extension Phase to Evaluate Safety, Tolerability, and Efficacy of BAN2401 in Subjects With Early Alzheimer’s Disease

    Summary
    EudraCT number
    		 2012-002843-11
    Trial protocol
    		 IT   SE   DE   GB   NL   ES  
    Global end of trial date
    10 Dec 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Dec 2025
    First version publication date
    26 Dec 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    BAN2401-G000-201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01767311
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Eisai Ltd.
    Sponsor organisation address
    European Knowledge Centre Mosquito Way, Hatfield, Hertfordshire, United Kingdom, AL10 9SN
    Public contact
    Eisai Europe Ltd., EMEA Medical Information, +44 (0)208 600 1400, EUMedInfo@eisai.net
    Scientific contact
    Eisai Europe Ltd., EMEA Medical Information, +44 (0)208 600 1400, EUMedInfo@eisai.net
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    10 Dec 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Dec 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of the core phase were to evaluate the efficacy of BAN2401 compared to placebo by establishing the dose regimen with at least 90% of the maximum effective dose (dmax) treatment effect (ED90) for BAN2401 on the Alzheimer’s Disease Composite Score (ADCOMS) at 12 months of treatment in subjects with Early Alzheimer’s Disease (EAD), defined as mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) – intermediate likelihood or mild AD dementia and to assess the safety and tolerability of 3 doses and 2 dose regimens of BAN2401 in subjects with EAD. The primary objective of the extension phase was to evaluate the long-term safety and tolerability of lecanemab in subjects with Early Alzheimer’s Disease.
    Protection of trial subjects
    This study was performed in full compliance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and all applicable local Good Clinical Practice (GCP) and regulations. This study is to be conducted in compliance with the protocol and in compliance with the EU Clinical Trial Regulation (CTR). All required study documentation is archived as required by regulatory authorities.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Dec 2012
    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
    Canada: 43
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Spain: 32
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    Italy: 19
    Country: Number of subjects enrolled
    Japan: 34
    Country: Number of subjects enrolled
    Korea, Republic of: 19
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Sweden: 8
    Country: Number of subjects enrolled
    United States: 685
    Worldwide total number of subjects
    854
    EEA total number of subjects
    69
    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)
    170
    From 65 to 84 years
    639
    85 years and over
    45

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study has been conducted in two phases: Core Study Phase and an Open-Label Extension (OLE) Phase. Subjects took part in the Core study at 149 investigative sites across the North America, Europe and Asia-Pacific. The OLE Phase was conducted at 56 investigative sites across the United States, Europe and Asia-Pacific.

    Pre-assignment
    Screening details
    		 A total of 3267 subjects were screened, of which 2411 subjects were screen failures, and 856 subjects were randomized. Out of 856, 854 subjects were treated in Core Study Phase, and 180 subjects were enrolled and treated in OLE Phase.

    Period 1
    Period 1 title
    Core Study Phase (18 months)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Core Study Phase: Placebo
    Arm description
    		 Subjects received lecanemab matching-placebo as 60-minute intravenous (IV) infusions, biweekly or monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab matched placebo in core study phase.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Lecanemab matching-placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lecanemab matching-placebo as 60-minute IV infusions, biweekly or monthly, up to 18 months.

    Arm title
    		 Core Study Phase: Lecanemab 2.5 mg/kg Biweekly
    Arm description
    		 Subjects received lecanemab 2.5 milligrams per kilogram (mg/kg) as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lecanemab 2.5 mg/kg
    Investigational medicinal product code
    BAN2401
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lecanemab 2.5 mg/kg as 60-minute IV infusions, biweekly, up to 18 months.

    Arm title
    		 Core Study Phase: Lecanemab 5 mg/kg Monthly
    Arm description
    		 Subjects received lecanemab 5 mg/kg as 60-minute IV infusions, monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lecanemab 5mg/kg
    Investigational medicinal product code
    BAN2401
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lecanemab 5mg/kg as 60-minute IV infusions, monthly, up to 18 months.

    Arm title
    		 Core Study Phase: Lecanemab 5 mg/kg Biweekly
    Arm description
    		 Subjects received lecanemab 5 mg/kg as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lecanemab 5mg/kg
    Investigational medicinal product code
    BAN2401
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lecanemab 5mg/kg as 60-minute IV infusions, biweekly, up to 18 months.

    Arm title
    		 Core Study Phase: Lecanemab 10 mg/kg Monthly
    Arm description
    		 Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lecanemab 10mg/kg
    Investigational medicinal product code
    BAN2401
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lecanemab 10mg/kg as 60-minute IV infusions, monthly, up to 18 months.

    Arm title
    		 Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Arm description
    		 Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lecanemab 10mg/kg
    Investigational medicinal product code
    BAN2401
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lecanemab 10mg/kg as 60-minute IV infusions, biweekly, up to 18 months.

    Number of subjects in period 1
    		Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Started
    245
    52
    51
    92
    253
    161
    Full Analysis Set (FAS)
    238
    52
    48
    89
    246
    152
    Safety Analysis Set (SAS)
    245
    52
    51
    92
    253
    161
    PD Analysis Set (Amyloid PET)
    99 [1]
    28 [2]
    28 [3]
    27 [4]
    89 [5]
    44 [6]
    Completed
    177
    35
    37
    61
    155
    87
    Not completed
    68
    17
    14
    31
    98
    74
         Consent withdrawn by subject
    23
    1
    5
    13
    37
    20
         Adverse event, non-fatal
    10
    4
    2
    5
    23
    12
         Other
    13
    7
    4
    4
    20
    31
         Subject Choice
    15
    5
    2
    7
    14
    8
         Lost to follow-up
    7
    -
    1
    2
    4
    3
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only applicable subjects were present in this analysis set.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only applicable subjects were present in this analysis set.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only applicable subjects were present in this analysis set.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only applicable subjects were present in this analysis set.
    [5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only applicable subjects were present in this analysis set.
    [6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only applicable subjects were present in this analysis set.
    Period 2
    Period 2 title
    OLE Phase (60 months)
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 OLE Phase: Lecanemab 10 mg/kg Biweekly
    Arm description
    		 Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, biweekly, up to 60 months. Subjects were followed up for 3 months after last dose of lecanemab in OLE phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lecanemab 10mg/kg
    Investigational medicinal product code
    BAN2401
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Lecanemab 10mg/kg as 60-minute IV infusions, biweekly, up to 60 months.

    Number of subjects in period 2 [7]
    		OLE Phase: Lecanemab 10 mg/kg Biweekly
    Started
    180
    Treated
    180
    Coming from Core Part: Placebo
    45
    ComingfromCore-2.5,5mg/kgQ2W,5 mg/kgQ4W
    37 [8]
    ComingfromCorePart-10mg/kgQ4W
    60
    Coming fromCorePart-10mg/kgQ2W
    38 [9]
    Safety Analysis Set (SAS)
    180
    PD Analysis Set (Amyloid PET)
    105
    Completed
    39
    Not completed
    141
         Consent withdrawn by subject
    37
         Transition To Commercial LEQEMBI
    18
         Adverse event, non-fatal
    12
         Subject Choice
    37
         Other
    22
         Lost to follow-up
    3
         Treatment Terminated by Sponsor
    12
    Notes
    [7] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: The number of subjects who enrolled for OLE phase were different and not equal to that of the core phase.
    [8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only applicable subjects from core phase were part of this milestone.
    [9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only applicable subjects were present in this analysis set.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Core Study Phase: Placebo
    Reporting group description
    		 Subjects received lecanemab matching-placebo as 60-minute intravenous (IV) infusions, biweekly or monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab matched placebo in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 2.5 mg/kg Biweekly
    Reporting group description
    		 Subjects received lecanemab 2.5 milligrams per kilogram (mg/kg) as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 5 mg/kg Monthly
    Reporting group description
    		 Subjects received lecanemab 5 mg/kg as 60-minute IV infusions, monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 5 mg/kg Biweekly
    Reporting group description
    		 Subjects received lecanemab 5 mg/kg as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 10 mg/kg Monthly
    Reporting group description
    		 Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Reporting group description
    		 Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly Total
    Number of subjects
    		 245 52 51 92 253 161 854
    Age Categorical
    Units: subjects
        <=18 years
    		 0 0 0 0 0 0 0
        Between 18 and 65 years
    		 56 11 9 20 46 28 170
        >=65 years
    		 189 41 42 72 207 133 684
    Sex: Female, Male
    Units: subjects
        Female
    		 138 26 26 50 112 70 422
        Male
    		 107 26 25 42 141 91 432
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 10 4 1 3 10 10 38
        Not Hispanic or Latino
    		 235 48 50 89 243 151 816
        Unknown or Not Reported
    		 0 0 0 0 0 0 0
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 222 48 49 76 228 150 773
        Black or African American
    		 5 2 1 4 5 4 21
        Chinese
    		 1 0 0 0 0 0 1
        Japanese
    		 10 1 0 6 12 5 34
        Other Asian
    		 6 1 1 3 5 2 18
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0
        Native Hawaiian or other Pacific Islander
    		 0 0 0 0 0 0 0
        Other
    		 1 0 0 3 3 0 7
        Missing
    		 0 0 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Core Study Phase: Placebo
    Reporting group description
    		 Subjects received lecanemab matching-placebo as 60-minute intravenous (IV) infusions, biweekly or monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab matched placebo in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 2.5 mg/kg Biweekly
    Reporting group description
    		 Subjects received lecanemab 2.5 milligrams per kilogram (mg/kg) as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 5 mg/kg Monthly
    Reporting group description
    		 Subjects received lecanemab 5 mg/kg as 60-minute IV infusions, monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 5 mg/kg Biweekly
    Reporting group description
    		 Subjects received lecanemab 5 mg/kg as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 10 mg/kg Monthly
    Reporting group description
    		 Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Reporting group description
    		 Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.
    Reporting group title
    OLE Phase: Lecanemab 10 mg/kg Biweekly
    Reporting group description
    		 Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, biweekly, up to 60 months. Subjects were followed up for 3 months after last dose of lecanemab in OLE phase.

    Subject analysis set title
    OLE Phase: Lecanemab 10 mg/kg Biweekly
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, biweekly, up to 60 months. Subjects were followed up for 3 months after last dose of lecanemab in OLE phase.

    Subject analysis set title
    Core Phase: Lecanemab 10 mg/kg Biweekly
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Subject analysis set title
    OLE Phase: Newly Treated Core Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects randomized to placebo in the Core Study and newly-treated with lecanemab 10 mg/kg, biweekly, in the OLE phase.

    Subject analysis set title
    OLE Phase: Re-treated Core Lower Doses
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects randomized to 2.5 mg/kg biweekly, 5 mg/kg monthly, or 5 mg/kg biweekly in the Core Study and re-treated with lecanemab 10 mg/kg, biweekly, in the OLE phase.

    Subject analysis set title
    OLE Phase: Re-treated Core 10 mg/kg Monthly
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects randomized to 10 mg/kg monthly in the Core Study and re-treated with lecanemab 10 mg/kg, biweekly, in the OLE phase.

    Subject analysis set title
    OLE Phase: Re-treated Core 10 mg/kg Biweekly
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects randomized to 10 mg/kg biweekly in the Core Study and re-treated with lecanemab 10 mg/kg, biweekly, in the OLE phase.

    Subject analysis set title
    OLE Phase: Newly Treated Core Placebo
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects randomized to placebo in the Core Study and newly-treated with lecanemab 10 mg/kg, biweekly, in the OLE phase.

    Subject analysis set title
    OLE Phase: Re-treated Core Lower Doses
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects randomized to 2.5 mg/kg biweekly, 5 mg/kg monthly, or 5 mg/kg biweekly in the Core Study and re-treated with lecanemab 10 mg/kg, biweekly, in the OLE phase.

    Subject analysis set title
    OLE Phase: Re-treated Core 10 mg/kg Monthly
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects randomized to 10 mg/kg monthly in the Core Study and re-treated with lecanemab 10 mg/kg, biweekly, in the OLE phase.

    Subject analysis set title
    OLE Phase: Re-treated Core 10 mg/kg Biweekly
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects randomized to 10 mg/kg biweekly in the Core Study and re-treated with lecanemab 10 mg/kg, biweekly, in the OLE phase.

    Primary: Core Study Phase: Change from Baseline in Alzheimer's Disease Composite Score (ADCOMS) at Month 12

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    End point title
    		 Core Study Phase: Change from Baseline in Alzheimer's Disease Composite Score (ADCOMS) at Month 12 [1]
    End point description
    The ADCOMS is a composite score that comprises 4/14 items from the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), 2 items from the Mini Mental State Examination (MMSE), and all items from the Clinical Dementia Rating (CDR). Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score means greater impairment. Change from baseline was analyzed using Bayesian analysis. Data presented are posterior mean and posterior standard deviation. The primary analysis indicated that the 10mg/kg biweekly dose had a 64% probability of being better than placebo with 25% less decline. FAS was the group of randomized subjects who received at least 1 dose of study drug and had baseline and at least 1 post dose primary efficacy measurement.
    End point type
    Primary
    End point timeframe
    Core Study Phase: at Month 12
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was evaluated for this end point.
    End point values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    238
    52
    48
    89
    246
    152
    Units: score on a scale
        arithmetic mean (standard deviation)
    0.113 ( 0.012 )
    0.134 ( 0.024 )
    0.119 ( 0.021 )
    0.116 ( 0.016 )
    0.084 ( 0.011 )
    0.077 ( 0.014 )
    No statistical analyses for this end point

    Primary: Core Study Phase: Number of Subjects with all Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Core Study Phase: Number of Subjects with all Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [2]
    End point description
    A TEAE is defined as an adverse event (AE) that emerged during treatment or within 90 days following last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (that is, subject is at immediate risk of death from AE as it occurs, this does not include an event that, has it occurred in a more severe form or is allowed to continue, might have caused death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect (in child of a subject who is exposed to study drug). Safety Analysis Set.
    End point type
    Primary
    End point timeframe
    From first dose of the study drug (Week 1) up to 90 days after last dose of study drug (up to 21 months)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was evaluated for this end point.
    End point values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    245
    52
    51
    92
    253
    161
    Units: subjects
        TEAEs
    216
    46
    48
    81
    238
    139
        SAEs
    43
    10
    4
    16
    31
    25
    No statistical analyses for this end point

    Primary: OLE Phase: Number of Subjects with all TEAEs and SAEs

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    End point title
    		 OLE Phase: Number of Subjects with all TEAEs and SAEs [3]
    End point description
    A TEAE is defined as an AE that emerged during treatment or within 30 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (that is, subject is at immediate risk of death from the adverse event as it occurs, this does not include an event that, has it occurred in a more severe form or is allowed to continue, might have cause death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect (in the child of a subject who is exposed to the study drug). SAS was group of subjects who received at least one active dose of study drug.
    End point type
    Primary
    End point timeframe
    From first dose of the study drug (Week 1) up to 30 days after last dose of study drug (up to 61 months)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This end point was assessed for OLE phase only.
    End point values
    		 OLE Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    180
    Units: subjects
        TEAEs
    173
        SAEs
    60
    No statistical analyses for this end point

    Secondary: Core Study Phase: Change from Baseline at Months 12 and 18 in Brain Amyloid Pathophysiology as Measured by Amyloid Positron Emission Tomography (PET)

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    End point title
    		 Core Study Phase: Change from Baseline at Months 12 and 18 in Brain Amyloid Pathophysiology as Measured by Amyloid Positron Emission Tomography (PET)
    End point description
    Amyloid plaque load was identified by PET using 2 tracers (florbetapir and flutemetamol). The imaging uptake was determined via standard uptake value ratio (SUVr) versus a reference region. The SUVr is a quantitative tool and refers to the ratio of the global cortical average as compared to a reference region of choice. Whole cerebellum mask was used as the reference region of choice in this study. PET SUVr values were converted to Centiloid units. Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition. The pharmacodynamic (PD) analysis set was the group of subjects who had sufficient amyloid PET data to derive at least 1 amyloid PET parameter. Here, 'n' refers to number of subjects analyzed at given time points.
    End point type
    Secondary
    End point timeframe
    Core Study Phase: at Months 12 and 18
    End point values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    99
    28
    28
    27
    89
    44
    Units: centiloids
    least squares mean (standard error)
        Change at Month 12 (n= 96, 27, 27, 25, 88, 43)
    -2.154 ( 2.448 )
    -14.733 ( 4.345 )
    -16.877 ( 4.350 )
    -37.796 ( 4.522 )
    -41.704 ( 2.682 )
    -62.827 ( 3.486 )
        Change at Month 18 (n= 88, 23, 23, 24, 82, 37)
    1.004 ( 2.651 )
    -22.404 ( 4.822 )
    -31.168 ( 4.844 )
    -46.217 ( 4.879 )
    -53.412 ( 2.877 )
    -72.495 ( 3.870 )
    No statistical analyses for this end point

    Secondary: Core Study Phase: Change from Baseline in ADCOMS at Month 18

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    End point title
    		 Core Study Phase: Change from Baseline in ADCOMS at Month 18
    End point description
    The ADCOMS is a composite score that comprises 4/14 items from the ADAS-cog, 2 items from the MMSE, and all items from the CDR. Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score means greater impairment. FAS was the group of randomized subjects who received at least 1 dose of study drug and had baseline and at least 1 post dose primary efficacy measurement. Here, 'Number of Subjects Analyzed' refers to number of subjects analyzed at given time point.
    End point type
    Secondary
    End point timeframe
    Core Study Phase: at Month 18
    End point values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    160
    33
    35
    61
    146
    79
    Units: score on a scale
        least squares mean (standard error)
    0.193 ( 0.017 )
    0.173 ( 0.035 )
    0.192 ( 0.035 )
    0.199 ( 0.026 )
    0.166 ( 0.018 )
    0.136 ( 0.022 )
    No statistical analyses for this end point

    Secondary: Core Study Phase: Change from Baseline in Clinical Dementia Rating- Sum of Boxes (CDR-SB) at Months 12 and 18

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    End point title
    		 Core Study Phase: Change from Baseline in Clinical Dementia Rating- Sum of Boxes (CDR-SB) at Months 12 and 18
    End point description
    The CDR is a clinical scale that describes 5 degrees of impairment in performance on each of 6 categories of function including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The ratings of degree of impairment obtained on each of the 6 categories of function are synthesized into 1 global rating of dementia CDR score (ranging from 0 to 3). A sum of boxes score provides an additional measure of change where each category has a maximum possible score of 3 points and the total score is a sum of the category scores giving a total possible score of 0 to 18 with higher scores indicating more impairment. The full analysis set was the group of randomized subjects who received at least 1 dose of study drug and had baseline and at least 1 post dose primary efficacy measurement. Here, 'n' refers to number of subjects analyzed at given time points.
    End point type
    Secondary
    End point timeframe
    Core Study Phase: at Months 12 and 18
    End point values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    238
    52
    48
    89
    246
    152
    Units: score on a scale
    least squares mean (standard error)
        Change at Month 12 (n= 188, 38, 42, 70, 166, 94)
    0.911 ( 0.124 )
    1.038 ( 0.257 )
    1.277 ( 0.253 )
    0.945 ( 0.194 )
    0.705 ( 0.133 )
    0.568 ( 0.163 )
        Change at Month 18 (n= 161, 34, 36, 67, 149, 84)
    1.499 ( 0.160 )
    1.227 ( 0.338 )
    1.713 ( 0.334 )
    1.463 ( 0.250 )
    1.248 ( 0.169 )
    1.102 ( 0.213 )
    No statistical analyses for this end point

    Secondary: Core Study Phase: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Months 12 and 18

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    End point title
    		 Core Study Phase: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at Months 12 and 18
    End point description
    The ADAS-Cog is a cognitive scale which evaluates 14 items- memory (word recall, delayed word recall, and word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope), constructional praxis (copying geometric designs), spoken language, language comprehension, word finding difficulty, ability to remember test instructions, maze, and number cancellation. The total score ranges from 0 to 90. Higher score indicates greater cognitive impairment. The full analysis set was the group of randomized subjects who received at least 1 dose of study drug and had baseline and at least 1 post dose primary efficacy measurement. Here, 'n' refers to number of subjects analyzed at given time points.
    End point type
    Secondary
    End point timeframe
    Core Study Phase: at Months 12 and 18
    End point values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    238
    52
    48
    89
    246
    152
    Units: score on a scale
    least squares mean (standard error)
        Change at Month 12 (n= 186, 38, 41, 69, 164, 94)
    2.842 ( 0.501 )
    4.251 ( 1.005 )
    3.426 ( 1.005 )
    3.297 ( 0.766 )
    2.200 ( 0.536 )
    1.481 ( 0.648 )
        Change at Month 18 (n= 158, 33, 34, 61, 146, 79)
    4.902 ( 0.617 )
    5.574 ( 1.275 )
    5.746 ( 1.279 )
    4.506 ( 0.959 )
    4.624 ( 0.652 )
    2.588 ( 0.811 )
    No statistical analyses for this end point

    Secondary: Core Study Phase: Change from Baseline in Cerebrospinal fluid (CSF) Biomarker Levels at Months 12 and 18

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    End point title
    		 Core Study Phase: Change from Baseline in Cerebrospinal fluid (CSF) Biomarker Levels at Months 12 and 18
    End point description
    The measurement of the amyloid proteins- Aβ(1-42) (amyloid beta monomer from amino acid 1 to 42), total (t)-tau, and phospho (p)-tau in CSF have been shown to be important biomarkers for alzheimer's disease. The PD analysis set was the group of subjects who had sufficient CSF data to derive at least 1 CSF parameter. Here, 'n' refers to number of subjects analyzed at given time points.
    End point type
    Secondary
    End point timeframe
    Core Study Phase: at Months 12 and 18
    End point values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    24
    7
    13
    20
    16
    12
    Units: picogram per milliliter (pg/mL)
    least squares mean (standard error)
        Month 12 in Aβ(1-42) (n= 22, 7, 13, 19, 16, 10)
    -8.008 ( 36.952 )
    49.921 ( 57.175 )
    89.009 ( 44.816 )
    152.271 ( 39.993 )
    137.036 ( 42.042 )
    286.542 ( 51.385 )
        Month 18 in Aβ(1-42) (n= 19, 5, 10, 14, 13, 9)
    -3.639 ( 38.228 )
    130.940 ( 63.467 )
    104.253 ( 48.358 )
    168.906 ( 43.762 )
    193.388 ( 44.454 )
    392.445 ( 53.603 )
        Month 12 in t-tau (n= 17, 6, 8, 14, 10, 7)
    -25.680 ( 47.937 )
    -92.678 ( 72.662 )
    -51.163 ( 65.398 )
    -61.933 ( 57.301 )
    -153.214 ( 58.215 )
    -39.101 ( 66.565 )
        Month 18 in t-tau (n= 15, 4, 6, 12, 8, 7)
    -70.490 ( 46.075 )
    -154.465 ( 76.475 )
    -128.914 ( 67.208 )
    -92.441 ( 56.026 )
    -102.221 ( 57.606 )
    66.279 ( 59.639 )
        Month 12 in p -tau (n= 22, 7, 13, 19, 16, 10)
    3.258 ( 4.834 )
    -2.451 ( 7.785 )
    -2.135 ( 5.848 )
    -3.810 ( 5.211 )
    -15.732 ( 5.542 )
    -9.732 ( 6.606 )
        Month 18 in p -tau (n= 19, 5, 10, 14, 13, 10)
    1.436 ( 4.335 )
    -6.496 ( 7.323 )
    -2.201 ( 5.434 )
    -10.508 ( 5.073 )
    -11.874 ( 5.023 )
    -10.880 ( 5.492 )
    No statistical analyses for this end point

    Secondary: Core Study Phase: Change from Baseline in Total Hippocampal Volume at Months 6, 12 and 18

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    End point title
    		 Core Study Phase: Change from Baseline in Total Hippocampal Volume at Months 6, 12 and 18
    End point description
    Total hippocampal volume is measured by volumetric magnetic resonance imaging (vMRI). Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total hippocampal volume is calculated by summing up right and left hippocampal volumes. The PD analysis set was the group of subjects who had sufficient vMRI data to derive at least 1 vMRI parameter. Here, 'n' refers to number of subjects analyzed at given time points.
    End point type
    Secondary
    End point timeframe
    Core Study Phase: at Months 6, 12 and 18
    End point values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    209
    41
    46
    73
    188
    99
    Units: cubic millimeters
    least squares mean (standard error)
        Change at Month 6 (n= 199, 39, 44, 72, 185, 91)
    -112.881 ( 9.973 )
    -100.640 ( 19.511 )
    -127.152 ( 18.495 )
    -112.335 ( 15.102 )
    -99.922 ( 10.981 )
    -120.262 ( 13.979 )
        Change at Month 12 (n= 178, 40, 43, 66, 158, 83)
    -187.122 ( 10.196 )
    -189.687 ( 19.422 )
    -200.721 ( 18.640 )
    -213.074 ( 15.376 )
    -172.774 ( 11.271 )
    -204.058 ( 14.233 )
        Change at Month 18 (n= 162, 34, 39, 55, 144, 72)
    -257.297 ( 10.394 )
    -305.254 ( 20.161 )
    -304.600 ( 19.053 )
    -297.469 ( 15.955 )
    -264.868 ( 11.448 )
    -276.740 ( 14.681 )
    No statistical analyses for this end point

    Secondary: Core Study Phase: Change from Baseline in Left and Right Hippocampal Volume at Months 6, 12 and 18

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    End point title
    		 Core Study Phase: Change from Baseline in Left and Right Hippocampal Volume at Months 6, 12 and 18
    End point description
    Left Hippocampal Volume (LHV) and Right Hippocampus Volume (RHV) are measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Left and right hippocampal volumes represent a summary measure in the left and right hippocampal regions. The PD analysis set was the group of subjects who had sufficient vMRI data to derive at least 1 vMRI parameter. Here, 'n' refers to number of subjects analyzed at given time points.
    End point type
    Secondary
    End point timeframe
    Core Study Phase: at Months 6, 12 and 18
    End point values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    209
    41
    46
    73
    188
    99
    Units: cubic millimeters
    least squares mean (standard error)
        Month 6 in LHV (n= 199, 39, 44, 72, 185, 91)
    -54.087 ( 5.457 )
    -50.434 ( 10.664 )
    -61.886 ( 10.120 )
    -55.660 ( 8.263 )
    -51.235 ( 6.009 )
    -65.037 ( 7.650 )
        Month 12 in LHV (n= 178, 40, 43, 66, 158, 83)
    -93.718 ( 5.580 )
    -93.988 ( 10.614 )
    -101.775 ( 10.200 )
    -103.744 ( 8.414 )
    -89.696 ( 6.169 )
    -109.026 ( 7.790 )
        Month 18 in LHV (n= 162, 34, 39, 55, 144, 72)
    -129.578 ( 5.689 )
    -147.500 ( 11.022 )
    -149.009 ( 10.428 )
    -149.244 ( 8.734 )
    -134.749 ( 6.266 )
    -142.666 ( 8.036 )
        Month 6 in RHV (n= 199, 39, 44, 72, 185, 91)
    -58.876 ( 5.765 )
    -51.454 ( 11.299 )
    -65.724 ( 10.700 )
    -56.881 ( 8.734 )
    -48.976 ( 6.344 )
    -55.242 ( 8.085 )
        Month 12 in RHV (n= 178, 40, 43, 66, 158, 53)
    -93.503 ( 5.897 )
    -96.952 ( 11.246 )
    -99.397 ( 10.785 )
    -109.513 ( 8.896 )
    -83.346 ( 6.515 )
    -94.972 ( 8.235 )
        Month 18 in RHV (n= 162, 34, 39, 55, 144, 72)
    -127.823 ( 6.014 )
    -158.981 ( 11.684 )
    -156.004 ( 11.030 )
    -148.467 ( 9.239 )
    -130.389 ( 6.620 )
    -134.090 ( 8.500 )
    No statistical analyses for this end point

    Secondary: Core Study Phase: Change from Baseline in Whole Brain Volume at Months 6, 12 and 18

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    End point title
    		 Core Study Phase: Change from Baseline in Whole Brain Volume at Months 6, 12 and 18
    End point description
    Whole brain volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Whole brain volume represents a summary measure of total brain parenchyma which includes the cerebrum, basal ganglia, diencephalon, and cerebellum. The PD analysis set was the group of subjects who had sufficient vMRI data to derive at least 1 vMRI parameter. Here, 'n' refers to number of subjects analyzed at given time points.
    End point type
    Secondary
    End point timeframe
    Core Study Phase: at Months 6, 12 and 18
    End point values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    209
    41
    46
    73
    188
    99
    Units: cubic millimeters
    least squares mean (standard error)
        Change at Month 6 (n= 198, 38, 43, 72, 183, 91)
    -8874.418 ( 885.172 )
    -10020.371 ( 1732.015 )
    -13726.830 ( 1656.368 )
    -11237.195 ( 1339.685 )
    -9656.914 ( 979.072 )
    -12613.175 ( 1240.020 )
        Change at Month 12 (n= 177, 38, 42, 66, 156, 82)
    -15489.162 ( 904.604 )
    -18027.826 ( 1734.486 )
    -19721.462 ( 1669.211 )
    -19616.201 ( 1363.106 )
    -16900.972 ( 1004.379 )
    -21913.188 ( 1264.436 )
        Change at Month 18 (n= 162, 32, 38, 55, 144, 72)
    -21775.855 ( 921.131 )
    -26987.109 ( 1805.216 )
    -27972.208 ( 1706.449 )
    -26520.544 ( 1413.525 )
    -25030.190 ( 1017.492 )
    -29894.193 ( 1300.815 )
    No statistical analyses for this end point

    Secondary: Core Study Phase: Change from Baseline in Total Ventricular Volume at Months 6, 12 and 18

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    End point title
    		 Core Study Phase: Change from Baseline in Total Ventricular Volume at Months 6, 12 and 18
    End point description
    Total ventricular volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total ventricular volume represents a summary measure of total including right and left lateral ventricles, third ventricle and fourth ventricle of brain. The PD analysis set was the group of subjects who had sufficient vMRI data to derive at least 1 vMRI parameter. Here, 'n' refers to number of subjects analyzed at given time points.
    End point type
    Secondary
    End point timeframe
    Core Study Phase: at Months 6, 12 and 18
    End point values
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Number of subjects analysed
    209
    41
    46
    73
    188
    99
    Units: cubic millimeters
    least squares mean (standard error)
        Change at Month 6 (n= 199, 39, 44, 72, 185, 92)
    1903.815 ( 233.516 )
    2052.336 ( 454.966 )
    2528.554 ( 432.705 )
    2486.366 ( 353.749 )
    2121.032 ( 257.082 )
    3110.184 ( 326.434 )
        Change at Month 12 (n= 178, 40, 43, 66, 158, 82)
    3590.079 ( 238.650 )
    4043.315 ( 452.855 )
    4824.827 ( 436.020 )
    4330.876 ( 359.983 )
    4322.248 ( 263.766 )
    5529.833 ( 333.677 )
        Change at Month 18 (n= 161, 34, 39, 55, 144, 72)
    5344.503 ( 243.477 )
    6250.430 ( 469.844 )
    7265.785 ( 445.381 )
    6338.779 ( 373.274 )
    6504.053 ( 267.760 )
    7662.459 ( 343.216 )
    No statistical analyses for this end point

    Secondary: OLE Phase: Change from OLE Baseline in Brain Amyloid Levels as Measured by Amyloid PET

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    End point title
    		 OLE Phase: Change from OLE Baseline in Brain Amyloid Levels as Measured by Amyloid PET
    End point description
    Amyloid plaque load was identified by PET using 2 tracers (florbetapir and flutemetamol). The imaging uptake was determined via SUVr versus a reference region. SUVr is a quantitative tool and refers to ratio of global cortical average as compared to a reference region of choice. Whole cerebellum mask was used as reference region of choice in this study. PET SUVr values were converted to Centiloid units. Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents amount of global amyloid deposition. Change from OLE baseline was analyzed using the Mixed Model for Repeated Measures (MMRM) with Core Study treatment group, visit, Core Study treatment group by visit interaction, APOE4 status as fixed effects, and OLE baseline value and Gap duration as covariates. OLE PD Analysis Set was group of subjects who had sufficient PD data to derive at least 1 PD parameter during OLE Phase.
    End point type
    Secondary
    End point timeframe
    OLE Phase: at Months 3, 6, 12, 24, 36 and 48
    End point values
    		 OLE Phase: Newly Treated Core Placebo OLE Phase: Re-treated Core Lower Doses OLE Phase: Re-treated Core 10 mg/kg Monthly OLE Phase: Re-treated Core 10 mg/kg Biweekly
    Number of subjects analysed
    27 [4]
    20
    36
    22
    Units: centiloids
    arithmetic mean (standard error)
        Change at Month 3 (n= 9, 9, 18, 10)
    -18.260 ( 5.481 )
    -9.562 ( 5.555 )
    -10.136 ( 8.045 )
    -27.575 ( 4.302 )
        Change at Month 6 (n= 11, 7, 11, 10)
    -32.208 ( 5.452 )
    -11.929 ( 6.833 )
    -21.253 ( 5.717 )
    -21.606 ( 4.481 )
        Change at Month 12 (n= 19, 13, 25, 18)
    -50.951 ( 5.070 )
    -27.162 ( 5.403 )
    -27.927 ( 6.024 )
    -22.769 ( 3.868 )
        Change at Month 24 (n= 17, 14, 26, 13)
    -60.300 ( 5.772 )
    -36.304 ( 5.605 )
    -34.646 ( 4.417 )
    -30.715 ( 5.066 )
        Change at Month 36 (n= 13, 10, 17, 9)
    -65.243 ( 7.544 )
    -38.383 ( 6.356 )
    -40.367 ( 4.906 )
    -33.116 ( 5.783 )
        Change at Month 48 (n= 9, 7, 12, 8)
    -66.598 ( 7.185 )
    -38.249 ( 8.190 )
    -43.541 ( 5.848 )
    -32.976 ( 5.655 )
    Notes
    [4] - Here, 'n' refers to number of subjects analyzed at given timepoints.
    No statistical analyses for this end point

    Secondary: OLE Phase: Change from end of Core Study at the Baseline of OLE Phase in Brain Amyloid Levels as Measured by Amyloid PET

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    End point title
    		 OLE Phase: Change from end of Core Study at the Baseline of OLE Phase in Brain Amyloid Levels as Measured by Amyloid PET
    End point description
    Amyloid plaque load was identified by PET using 2 tracers (florbetapir and flutemetamol). The imaging uptake was determined via standard uptake value ratio (SUVr) versus a reference region. The SUVr is a quantitative tool and refers to the ratio of the global cortical average as compared to a reference region of choice. Whole cerebellum mask was used as the reference region of choice in this study. PET SUVr values were converted to Centiloid units. Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition. The OLE enrolled set was the group of subjects who were enrolled in OLE phase. Here, 'n' refers to number of subjects analyzed at given time points.
    End point type
    Secondary
    End point timeframe
    Core Study: at Month 18, OLE Phase: Baseline
    End point values
    		 OLE Phase: Newly Treated Core Placebo OLE Phase: Re-treated Core Lower Doses OLE Phase: Re-treated Core 10 mg/kg Monthly OLE Phase: Re-treated Core 10 mg/kg Biweekly
    Number of subjects analysed
    45
    37
    60
    38
    Units: centiloids
    arithmetic mean (standard deviation)
        At end of core study-at Month 18(n= 13,6,24,13)
    12.077 ( 27.7765 )
    -50.610 ( 20.3136 )
    -54.491 ( 33.4376 )
    -78.022 ( 27.4337 )
        Change at OLE Baseline(n= 16,9,26,15)
    0.303 ( 25.4131 )
    -19.673 ( 31.7079 )
    -43.984 ( 37.7811 )
    -61.031 ( 37.6563 )
    No statistical analyses for this end point

    Secondary: OLE Phase: Percentage of Amyloid Positive Subjects over Time

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    End point title
    		 OLE Phase: Percentage of Amyloid Positive Subjects over Time
    End point description
    Percentage of amyloid positive subjects over time was reported. Subjects who had Amyloid PET (using Centiloid scales) values greater than or equal to 30.00 were considered as amyloid positive. The OLE PD analysis set was the group of subjects who had sufficient PD data to derive at least 1 PD parameter during the OLE Phase. Here, 'n' refers to number of subjects analyzed at given time points.
    End point type
    Secondary
    End point timeframe
    OLE Phase: Baseline, at Months 3, 6, 12, 24, 36 and 48
    End point values
    		 OLE Phase: Newly Treated Core Placebo OLE Phase: Re-treated Core Lower Doses OLE Phase: Re-treated Core 10 mg/kg Monthly OLE Phase: Re-treated Core 10 mg/kg Biweekly
    Number of subjects analysed
    27
    20
    36
    22
    Units: percentage of subjects
    number (not applicable)
        Amyloid Positivity at Baseline (n= 27, 20, 36, 22)
    92.6
    75.0
    63.9
    22.7
        Month 3 (n= 9, 9, 18, 10)
    66.7
    44.4
    44.4
    0
        Month 6 (n= 11, 7, 11, 10)
    45.5
    57.1
    45.5
    20.0
        Month 12 (n= 19, 13, 25, 18)
    36.8
    30.8
    40.0
    11.1
        Month 24 (n= 17, 14, 26, 13)
    5.9
    21.4
    15.4
    0
        Month 36 (n= 13, 10, 17,9)
    15.4
    20.0
    0
    0
        Month 48 (n= 9, 7, 12, 8)
    0
    28.6
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Core Phase: From first dose of the study drug (Week 1) up to 90 days after last dose of study drug (up to 21 months); OLE Phase: From first dose of the study drug (Week 1) up to 30 days after last dose of study drug (up to 61 months)
    Adverse event reporting additional description
    Adverse events were collected for all subjects who were in SAS (Core: group of subjects who received at least 1 dose of study drug and had at least 1 post dose safety assessment; OLE: group of subjects who received at least 1 active dose of study drug). MedDRA Version is 20.1 for core and 25.0 for OLE.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1, 25.0
    Reporting groups
    Reporting group title
    Core Study Phase: Placebo
    Reporting group description
    		 Subjects received lecanemab matching-placebo as 60-minute IV infusions, biweekly or monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab matched placebo in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 2.5 mg/kg Biweekly
    Reporting group description
    		 Subjects received lecanemab 2.5 mg/kg as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 5 mg/kg Monthly
    Reporting group description
    		 Subjects received lecanemab 5 mg/kg as 60-minute IV infusions, monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 5 mg/kg Biweekly
    Reporting group description
    		 Subjects received lecanemab 5 mg/kg as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 10 mg/kg Monthly
    Reporting group description
    		 Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, monthly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    Core Study Phase: Lecanemab 10 mg/kg Biweekly
    Reporting group description
    		 Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, biweekly, up to 18 months. Subjects were followed up for 3 months after last dose of lecanemab in core study phase.

    Reporting group title
    OLE Phase: Lecanemab 10 mg/kg Biweekly
    Reporting group description
    		 Subjects received lecanemab 10 mg/kg as 60-minute IV infusions, biweekly, up to 60 months. Subjects were followed up for 3 months after last dose of lecanemab in OLE phase.

    Serious adverse events
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly OLE Phase: Lecanemab 10 mg/kg Biweekly
    Total subjects affected by serious adverse events
         subjects affected / exposed
    43 / 245 (17.55%)
    10 / 52 (19.23%)
    4 / 51 (7.84%)
    16 / 92 (17.39%)
    31 / 253 (12.25%)
    25 / 161 (15.53%)
    60 / 180 (33.33%)
         number of deaths (all causes)
    2
    2
    0
    1
    2
    0
    5
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    0 / 245 (0.00%)
    1 / 52 (1.92%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ductal adenocarcinoma of pancreas
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sarcoma
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer metastatic
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma stage III
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine carcinoma
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Metastases to central nervous system
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Malignant neoplasm of unknown primary site
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Vascular disorders
    Internal haemorrhage
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Axillary vein thrombosis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Cyst
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    2 / 253 (0.79%)
    2 / 161 (1.24%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulcer haemorrhage
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vaginal prolapse
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    2 / 161 (1.24%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    2 / 161 (1.24%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    0 / 245 (0.00%)
    2 / 52 (3.85%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Aspiration
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Agitation
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aggression
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device breakage
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatinine abnormal
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    1 / 51 (1.96%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    4 / 245 (1.63%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    7 / 180 (3.89%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaw fracture
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    3 / 180 (1.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Splenic rupture
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal cord injury
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Sternal fracture
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    2 / 245 (0.82%)
    1 / 52 (1.92%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haemorrhage
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    3 / 180 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Head injury
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fractured coccyx
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniofacial fracture
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural hypotension
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic renal injury
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary contusion
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 245 (0.00%)
    1 / 52 (1.92%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 245 (0.00%)
    1 / 52 (1.92%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    1 / 253 (0.40%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 245 (0.00%)
    1 / 52 (1.92%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    0 / 245 (0.00%)
    1 / 52 (1.92%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Nervous system disorders
    Altered state of consciousness
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amyloid related imaging abnormalities
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    3 / 161 (1.86%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aphasia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral artery thrombosis
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral microhaemorrhage
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    2 / 161 (1.24%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolic stroke
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Focal dyscognitive seizures
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic transformation stroke
         subjects affected / exposed
    0 / 245 (0.00%)
    1 / 52 (1.92%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemic seizure
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Normal pressure hydrocephalus
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    3 / 245 (1.22%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    1 / 253 (0.40%)
    1 / 161 (0.62%)
    3 / 180 (1.67%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    2 / 51 (3.92%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    1 / 161 (0.62%)
    4 / 180 (2.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 0
    1 / 1
    1 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amyloid related imaging abnormality-oedema/effusion
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acquired epileptic aphasia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Superficial siderosis of central nervous system
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural hygroma
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic encephalopathy
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thalamic infarction
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal mass
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 245 (0.41%)
    1 / 52 (1.92%)
    1 / 51 (1.96%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal food impaction
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis acute
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    3 / 180 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    1 / 51 (1.96%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    2 / 161 (1.24%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    4 / 245 (1.63%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridial sepsis
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    4 / 180 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    3 / 180 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    1 / 92 (1.09%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal infection
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    2 / 180 (1.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypernatraemia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    1 / 253 (0.40%)
    0 / 161 (0.00%)
    0 / 180 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    1 / 180 (0.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Core Study Phase: Placebo Core Study Phase: Lecanemab 2.5 mg/kg Biweekly Core Study Phase: Lecanemab 5 mg/kg Monthly Core Study Phase: Lecanemab 5 mg/kg Biweekly Core Study Phase: Lecanemab 10 mg/kg Monthly Core Study Phase: Lecanemab 10 mg/kg Biweekly OLE Phase: Lecanemab 10 mg/kg Biweekly
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    212 / 245 (86.53%)
    46 / 52 (88.46%)
    48 / 51 (94.12%)
    80 / 92 (86.96%)
    237 / 253 (93.68%)
    135 / 161 (83.85%)
    169 / 180 (93.89%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma of skin
         subjects affected / exposed
    4 / 245 (1.63%)
    3 / 52 (5.77%)
    1 / 51 (1.96%)
    2 / 92 (2.17%)
    3 / 253 (1.19%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences all number
    5
    3
    3
    2
    3
    1
    0
    Basal cell carcinoma
         subjects affected / exposed
    7 / 245 (2.86%)
    4 / 52 (7.69%)
    2 / 51 (3.92%)
    6 / 92 (6.52%)
    4 / 253 (1.58%)
    3 / 161 (1.86%)
    12 / 180 (6.67%)
         occurrences all number
    12
    4
    2
    8
    5
    5
    16
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    28 / 245 (11.43%)
    3 / 52 (5.77%)
    6 / 51 (11.76%)
    13 / 92 (14.13%)
    21 / 253 (8.30%)
    17 / 161 (10.56%)
    47 / 180 (26.11%)
         occurrences all number
    40
    3
    10
    20
    26
    21
    82
    Contusion
         subjects affected / exposed
    7 / 245 (2.86%)
    2 / 52 (3.85%)
    5 / 51 (9.80%)
    6 / 92 (6.52%)
    11 / 253 (4.35%)
    7 / 161 (4.35%)
    18 / 180 (10.00%)
         occurrences all number
    7
    2
    6
    9
    13
    8
    20
    Infusion related reaction
         subjects affected / exposed
    8 / 245 (3.27%)
    3 / 52 (5.77%)
    4 / 51 (7.84%)
    11 / 92 (11.96%)
    59 / 253 (23.32%)
    31 / 161 (19.25%)
    39 / 180 (21.67%)
         occurrences all number
    12
    3
    5
    16
    111
    44
    98
    Skin laceration
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    12 / 180 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    14
    Skin abrasion
         subjects affected / exposed
    8 / 245 (3.27%)
    0 / 52 (0.00%)
    1 / 51 (1.96%)
    1 / 92 (1.09%)
    13 / 253 (5.14%)
    4 / 161 (2.48%)
    11 / 180 (6.11%)
         occurrences all number
    8
    0
    1
    1
    16
    4
    11
    Procedural pain
         subjects affected / exposed
    4 / 245 (1.63%)
    3 / 52 (5.77%)
    2 / 51 (3.92%)
    2 / 92 (2.17%)
    4 / 253 (1.58%)
    4 / 161 (2.48%)
    0 / 180 (0.00%)
         occurrences all number
    7
    3
    3
    2
    4
    4
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    13 / 245 (5.31%)
    1 / 52 (1.92%)
    1 / 51 (1.96%)
    3 / 92 (3.26%)
    10 / 253 (3.95%)
    7 / 161 (4.35%)
    18 / 180 (10.00%)
         occurrences all number
    13
    1
    1
    5
    10
    7
    25
    Hypotension
         subjects affected / exposed
    5 / 245 (2.04%)
    2 / 52 (3.85%)
    3 / 51 (5.88%)
    2 / 92 (2.17%)
    5 / 253 (1.98%)
    2 / 161 (1.24%)
    11 / 180 (6.11%)
         occurrences all number
    5
    2
    3
    3
    5
    2
    15
    Nervous system disorders
    Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    30 / 180 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    49
    Amyloid related imaging abnormality-oedema/effusion
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    15 / 180 (8.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    30
    Dizziness
         subjects affected / exposed
    18 / 245 (7.35%)
    4 / 52 (7.69%)
    0 / 51 (0.00%)
    10 / 92 (10.87%)
    9 / 253 (3.56%)
    13 / 161 (8.07%)
    15 / 180 (8.33%)
         occurrences all number
    19
    5
    0
    12
    10
    18
    17
    Superficial siderosis of central nervous system
         subjects affected / exposed
    1 / 245 (0.41%)
    0 / 52 (0.00%)
    1 / 51 (1.96%)
    5 / 92 (5.43%)
    7 / 253 (2.77%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences all number
    1
    0
    1
    6
    8
    1
    0
    Cerebral microhaemorrhage
         subjects affected / exposed
    12 / 245 (4.90%)
    2 / 52 (3.85%)
    7 / 51 (13.73%)
    12 / 92 (13.04%)
    22 / 253 (8.70%)
    9 / 161 (5.59%)
    0 / 180 (0.00%)
         occurrences all number
    16
    2
    10
    14
    30
    12
    0
    Amyloid related imaging abnormalities
         subjects affected / exposed
    2 / 245 (0.82%)
    1 / 52 (1.92%)
    1 / 51 (1.96%)
    3 / 92 (3.26%)
    24 / 253 (9.49%)
    13 / 161 (8.07%)
    0 / 180 (0.00%)
         occurrences all number
    2
    1
    1
    3
    24
    13
    0
    Headache
         subjects affected / exposed
    25 / 245 (10.20%)
    9 / 52 (17.31%)
    4 / 51 (7.84%)
    17 / 92 (18.48%)
    43 / 253 (17.00%)
    23 / 161 (14.29%)
    17 / 180 (9.44%)
         occurrences all number
    34
    12
    5
    24
    58
    34
    18
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    10 / 180 (5.56%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    10
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    15 / 245 (6.12%)
    4 / 52 (7.69%)
    1 / 51 (1.96%)
    7 / 92 (7.61%)
    17 / 253 (6.72%)
    8 / 161 (4.97%)
    9 / 180 (5.00%)
         occurrences all number
    39
    5
    1
    8
    22
    14
    10
    Pyrexia
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    11 / 180 (6.11%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    25
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    9 / 180 (5.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    11
    Diarrhoea
         subjects affected / exposed
    12 / 245 (4.90%)
    5 / 52 (9.62%)
    7 / 51 (13.73%)
    12 / 92 (13.04%)
    16 / 253 (6.32%)
    12 / 161 (7.45%)
    11 / 180 (6.11%)
         occurrences all number
    14
    6
    8
    12
    22
    17
    14
    Nausea
         subjects affected / exposed
    10 / 245 (4.08%)
    1 / 52 (1.92%)
    4 / 51 (7.84%)
    8 / 92 (8.70%)
    15 / 253 (5.93%)
    6 / 161 (3.73%)
    12 / 180 (6.67%)
         occurrences all number
    14
    1
    6
    20
    25
    6
    13
    Vomiting
         subjects affected / exposed
    8 / 245 (3.27%)
    2 / 52 (3.85%)
    4 / 51 (7.84%)
    7 / 92 (7.61%)
    10 / 253 (3.95%)
    2 / 161 (1.24%)
    11 / 180 (6.11%)
         occurrences all number
    14
    3
    5
    15
    11
    2
    16
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    12 / 245 (4.90%)
    1 / 52 (1.92%)
    2 / 51 (3.92%)
    4 / 92 (4.35%)
    11 / 253 (4.35%)
    14 / 161 (8.70%)
    12 / 180 (6.67%)
         occurrences all number
    13
    2
    3
    6
    13
    16
    24
    Skin and subcutaneous tissue disorders
    Drug eruption
         subjects affected / exposed
    1 / 245 (0.41%)
    3 / 52 (5.77%)
    0 / 51 (0.00%)
    2 / 92 (2.17%)
    4 / 253 (1.58%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences all number
    1
    3
    0
    2
    5
    1
    0
    Erythema
         subjects affected / exposed
    2 / 245 (0.82%)
    0 / 52 (0.00%)
    3 / 51 (5.88%)
    1 / 92 (1.09%)
    1 / 253 (0.40%)
    1 / 161 (0.62%)
    0 / 180 (0.00%)
         occurrences all number
    2
    0
    3
    1
    1
    1
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    13 / 245 (5.31%)
    1 / 52 (1.92%)
    3 / 51 (5.88%)
    6 / 92 (6.52%)
    13 / 253 (5.14%)
    5 / 161 (3.11%)
    11 / 180 (6.11%)
         occurrences all number
    13
    1
    3
    7
    14
    5
    11
    Agitation
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    12 / 180 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    12
    Insomnia
         subjects affected / exposed
    7 / 245 (2.86%)
    3 / 52 (5.77%)
    3 / 51 (5.88%)
    3 / 92 (3.26%)
    7 / 253 (2.77%)
    2 / 161 (1.24%)
    0 / 180 (0.00%)
         occurrences all number
    7
    3
    4
    3
    7
    2
    0
    Anxiety
         subjects affected / exposed
    15 / 245 (6.12%)
    1 / 52 (1.92%)
    3 / 51 (5.88%)
    4 / 92 (4.35%)
    10 / 253 (3.95%)
    6 / 161 (3.73%)
    20 / 180 (11.11%)
         occurrences all number
    20
    1
    3
    4
    11
    6
    21
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    17 / 245 (6.94%)
    0 / 52 (0.00%)
    4 / 51 (7.84%)
    5 / 92 (5.43%)
    12 / 253 (4.74%)
    6 / 161 (3.73%)
    19 / 180 (10.56%)
         occurrences all number
    19
    0
    4
    6
    12
    6
    21
    Back pain
         subjects affected / exposed
    24 / 245 (9.80%)
    4 / 52 (7.69%)
    6 / 51 (11.76%)
    4 / 92 (4.35%)
    20 / 253 (7.91%)
    11 / 161 (6.83%)
    18 / 180 (10.00%)
         occurrences all number
    26
    4
    6
    4
    21
    11
    19
    Pain in extremity
         subjects affected / exposed
    10 / 245 (4.08%)
    1 / 52 (1.92%)
    2 / 51 (3.92%)
    7 / 92 (7.61%)
    8 / 253 (3.16%)
    3 / 161 (1.86%)
    9 / 180 (5.00%)
         occurrences all number
    10
    1
    2
    7
    8
    3
    10
    Muscle spasms
         subjects affected / exposed
    5 / 245 (2.04%)
    1 / 52 (1.92%)
    6 / 51 (11.76%)
    0 / 92 (0.00%)
    5 / 253 (1.98%)
    3 / 161 (1.86%)
    0 / 180 (0.00%)
         occurrences all number
    5
    2
    7
    0
    5
    3
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 245 (0.00%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    0 / 92 (0.00%)
    0 / 253 (0.00%)
    0 / 161 (0.00%)
    33 / 180 (18.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    36
    Bronchitis
         subjects affected / exposed
    15 / 245 (6.12%)
    0 / 52 (0.00%)
    0 / 51 (0.00%)
    2 / 92 (2.17%)
    9 / 253 (3.56%)
    4 / 161 (2.48%)
    0 / 180 (0.00%)
         occurrences all number
    15
    0
    0
    2
    10
    7
    0
    Nasopharyngitis
         subjects affected / exposed
    28 / 245 (11.43%)
    3 / 52 (5.77%)
    7 / 51 (13.73%)
    9 / 92 (9.78%)
    19 / 253 (7.51%)
    13 / 161 (8.07%)
    22 / 180 (12.22%)
         occurrences all number
    33
    4
    10
    15
    21
    19
    32
    Urinary tract infection
         subjects affected / exposed
    32 / 245 (13.06%)
    5 / 52 (9.62%)
    5 / 51 (9.80%)
    17 / 92 (18.48%)
    25 / 253 (9.88%)
    16 / 161 (9.94%)
    34 / 180 (18.89%)
         occurrences all number
    39
    6
    6
    26
    35
    21
    49
    Sinusitis
         subjects affected / exposed
    8 / 245 (3.27%)
    1 / 52 (1.92%)
    5 / 51 (9.80%)
    1 / 92 (1.09%)
    9 / 253 (3.56%)
    7 / 161 (4.35%)
    0 / 180 (0.00%)
         occurrences all number
    9
    1
    8
    1
    14
    7
    0
    Upper respiratory tract infection
         subjects affected / exposed
    41 / 245 (16.73%)
    7 / 52 (13.46%)
    7 / 51 (13.73%)
    10 / 92 (10.87%)
    22 / 253 (8.70%)
    19 / 161 (11.80%)
    18 / 180 (10.00%)
         occurrences all number
    52
    7
    9
    11
    24
    22
    27

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Apr 2013
    Amendment 1: For consistency to align with NIA-AA terminology, mild “Alzheimer’s” dementia was changed to mild “Alzheimer’s disease dementia”. • Clarified that all 3 clinical scales were to be assessed before diagnosis and to further clarify the role of Wechsler Memory Scale criteria in eligibility (for MCI due to AD only). • Clarified Inclusion Criterion 4 for MCI due to AD subjects with objective impairment in episodic memory according to Wechsler Memory Scale. Subjects who scored below the age-adjusted range (not above) were also eligible, and thus the Inclusion Criterion for MCI due to AD was revised to clarify this point. • Clarified exclusion criterion No. 11 regarding thyroid function, in order to enable subjects who were euthyroid, and otherwise well and suitable for the study, to be eligible. • Updated the definition of futility and how it was addressed. • Included sensitivity analyses for the primary endpoint, so to include analyses that did not censor data based on compliance or changes in medication for AD. • Revised prohibited concomitant medication criteria window from before Screening to before Baseline, so to allow subjects additional time to meet the criteria for concomitant medication. • Scheduled infusion window was increased from 3 to 8 days, so to minimize the number of missed infusions while still ensuring adequate exposure to study drug. • Clarified that the GDS was clinician-assisted. While subjects can usually report this information on their own, it was important to clarify that the instrument would be clinician-assisted in the event that a subject was not capable of self-reporting. • Clarification on collection of exploratory biomarker and pharmacogenomic samples, since exploratory biomarker and pharmacogenomic samples would not be collected in those countries whose local regulations require the return of these data to subjects.
    27 Jun 2013
    Amendment 2: Amyvid could now be used in the EU, as had been recently approved. • The imaging subgroup was comprised of subjects in the United States only, since it was anticipated relatively few subjects were imaged with Amyvid in the EU, so for consistency, only those subjects in the United States were in the imaging subgroup.
    18 Sep 2013
    Amendment 3: As requested by the Germany regulatory authorities through the VHP, home infusions were not to be allowed at study sites in Germany. • As requested by EU regulatory authorities through the VHP process, for study inclusion, MMSE scores had to be greater than or equal to 22 or less than or equal to 28 in France, Germany, Spain, Sweden, Netherlands, and United Kingdom.
    09 Jul 2014
    Amendment 4: As recommended by the DSMB, to allow for early detection of ARIA–E before the Visit 9 (Week 13) MRI scan, safety and vMRIs at Visit 7 (Week 9) were added. This measure was to prevent the further dosing of subjects with early ARIA–E • As recommended by the DSMB, after unblinded review of all asymptomatic and symptomatic cases of ARIA–E in Study 201, the randomization algorithm was modified so ApoE4 homozygous subjects were not randomized to BAN2401 10 mg/kg biweekly.
    11 Aug 2014
    Amendment 5: Further to Amendment 04, the VHP committee requested that subjects confirmed ApoE4 carriers (homozygous or heterozygous) were not to be randomized to the 10 mg/kg biweekly dose of BAN2401.
    20 Nov 2014
    Amendment 6: Since mild AD dementia subjects should also exhibit deficits in episodic memory to be eligible for the study, the inclusion criteria for WMS was revised to apply to all subjects, not only subjects with MCI due to AD. •Since positive amyloid load can be indicated by either PET or CSF Aβ(1-42), CSF was added as an eligibility criterion for amyloid load in the brain to allow for potential study expansion to sites and countries that might not have amyloid PET imaging capabilities. Subjects who consented to both amyloid PET and CSF subgroups needed a positive amyloid result in only 1 of the 2 measures. • Per the Netherland’s request via the VHP process, the inclusion criteria were revised to include subjects with a BMI of greater than 17 kg/m2. • Only subjects with hypothyroidism as indicated by elevated TSH were to be excluded. Other tests of thyroid function with results outside the normal range were only to be exclusionary if considered clinically significant by the investigator. • To allow continuous monitoring of the risk factors for development of ARIA unblinding of all subjects who underwent Early Termination due to ARIA was allowed. • To allow for the use of alternative imaging agents and options when the need arose, but maintaining consistency for the quantitative longitudinal assessment, any approved imaging agent could be used in the US, Canada, EU, or any region in which the study was conducted. • In those subjects consenting to CSF collection, CSF collection was moved to coincide to 2 to 4 days after the last visit at which study drug was administered at Visit 29 (Week 53; Month 12). This change allowed for collection of BAN2401 PK in CSF following dosing and coincided with the CSF Cmax. • So that CSF could be collected predose to determine Cmin for BAN2401 in CSF, the CSF collection was moved from Visit 42 to Visit 41. Serum PK samples were collected immediately after CSF sampling at Visit 29 and Visit 41.
    26 Jun 2015
    Amendment 7: In order to explore preliminary data in Japanese subjects for consistency of treatment effect between populations, 40 randomized Japanese subjects were to be enrolled. • Inclusion Criterion No. 7 was revised to specify that subjects must consent to both Baseline CSF and PET before the eligibility results for either subgroup study were confirmed. • Inclusion Criterion No. 16 was revised to account for subjects with EAD who may lack capacity to consent at Screening, and who had capacity to consent at Screening but may lose capacity to consent over time. • Since potential untoward effects were sufficiently characterized to allow safe flexibility, subjects were no longer required to remain in clinic for 2 hours following infusion at all visits. • Due to low participation in home infusion this option was stopped for subjects recruited after implementation of Amendment 07. However, subjects previously enrolled in the study who had opted for home infusions were allowed to continue with them. • Due to increased availability of approved agents in other regions, the amyloid PET substudy was expanded to outside the US. • To account for the enrollment rate, the overall duration of study was increased from 41 to 67 months with an approximate study end of June 2018. • To increase the statistical power and increase likelihood of detecting an effect on amyloid, the imaging substudy sample size was increased from 260 to 306 subjects.
    30 Jul 2015
    Amendment 7: Per request from European Regulatory Authorities a Visit 6 (Week 7) safety MRI was added for European sites only (this safety MRI is not accompanied by vMRI sequences).
    19 Feb 2016
    Amendment 8: A 60-month open-label Extension Phase was added, to be conducted only if early success was achieved at any interim analysis or at the Bayesian analysis at 12 months of treatment. The criterion for conducting this open-label Extension Phase was not met, and thus it was not implemented. However, subsequently a 24-month open-label Extension Phase was implemented (see Amendment 11, 14 Sep 2018). • Historical brain amyloid positive PET scans could be used for study eligibility upon evaluation by the central imaging CRO. However, historical PET scans were not to be used as Baseline scans for longitudinal assessments in the imaging subgroup. • BAN2401 had to be infused with a terminal in-line filter. • Skin rash due to study drug was to be considered an event of interest and subjects with skin rash need not be withdrawn from the study.
    09 Nov 2017
    Amendment 9: Key secondary objectives and endpoints were specified. • The Bayesian analysis of ADCOMS was extended to include the 18-month endpoint to aid identification of the simplest dose regimen with the highest predictive probability of being the ED90 dose. • It was also specified that the conventional analysis for change from Baseline in ADCOMS at 18 months was based on the ED90 dose identified from the 18-month Bayesian analysis.
    16 Mar 2018
    Amendment 10: Updated key secondary objectives and secondary objectives to emphasize disease pathophysiology based on 18-month data. • Updated analysis methods to account for the lack of ApoE4 carriers in the 10 mg/kg biweekly dose group due to the change in the middle of randomization following a Regulatory request by European Health Authorities in July 2014 (see Amendments 04 and 05).
    14 Sep 2018
    Amendment 11: An open-label Extension Phase was initiated following the Core Study to allow subjects to receive open-label BAN2401 10 mg/kg biweekly for up to 24 months (2 years), until the drug was commercially available in the country where the subject resided, or until the benefit to risk ratio from treatment with BAN2401 was no longer considered favorable, whichever came first. • Florbetapir was the sole imaging agent used in the open-label Extension Phase PET substudy. As the availability of florbetapir was limited outside of the United States and Japan, the open-label Extension Phase PET was performed in the United States and Japan only using florbetapir and only in subjects who had agreed to participate in the longitudinal PET substudy. • The CSF biomarker exploratory objective and endpoint was removed because of projected lack of enrollment in the substudy. • The drug product formulation was clarified because the current formulation of the drug product was being progressively phased out as stocks neared the end of their shelf life, to be replaced by a newer formulation. • All subjects in the open-label Extension Phase were to receive open-label BAN2401 10 mg/kg biweekly, and it was clarified that the DSMB was to monitor safety only in the Core Study. • The PK sampling times were updated in line with the early timepoint assessments in the open-label Extension Phase. • The clinical experience with BAN2401 was updated to reflect completed and ongoing study data.
    15 Nov 2018
    Amendment 12: The requirements for Baseline amyloid PET scan before dosing in the Extension Phase were revised. • Revised tracers for PET longitudinal substudy; revised PET longitudinal substudy assessment timing for subjects in Japan. • Modification of assessment of ARIA-H and ARIA–E. • The Extension Phase inclusion and exclusion criteria were updated. • Revised Extension Phase screening criteria for MRI assessment. • Revised concomitant medications.
    15 Nov 2018
    Amendment 13: Modification of the safety monitoring plan for ARIA–E at Japan sites only, based on consultation meeting with Pharmaceuticals and Medical Devices Agency in December 2018.

    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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