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    Clinical Trial Results:
    Continued Efficacy and Safety Monitoring of Solanezumab, an Anti-Amyloid β Antibody in Patients with Alzheimer's Disease

    Summary
    EudraCT number
    		 2010-021155-11
    Trial protocol
    		 DE   ES   IT   SE   GB  
    Global end of trial date
    17 Feb 2017

    Results information
    Results version number
    		 v1
    This version publication date
    28 Feb 2018
    First version publication date
    28 Feb 2018
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    H8A-MC-LZAO
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01127633
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 11935
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    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
    17 Feb 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Feb 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study is an open-label extension study in Alzheimer's patients who have completed participation in either solanezumab Clinical Trial H8A-MC-LZAM or H8A-MC-LZAN (2008-007926-21).
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Dec 2010
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 24 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 81
    Country: Number of subjects enrolled
    Australia: 60
    Country: Number of subjects enrolled
    Brazil: 72
    Country: Number of subjects enrolled
    Canada: 78
    Country: Number of subjects enrolled
    France: 45
    Country: Number of subjects enrolled
    Germany: 79
    Country: Number of subjects enrolled
    Italy: 86
    Country: Number of subjects enrolled
    Japan: 156
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 65
    Country: Number of subjects enrolled
    Poland: 43
    Country: Number of subjects enrolled
    Russian Federation: 28
    Country: Number of subjects enrolled
    Spain: 37
    Country: Number of subjects enrolled
    Sweden: 36
    Country: Number of subjects enrolled
    Taiwan: 49
    Country: Number of subjects enrolled
    United Kingdom: 35
    Country: Number of subjects enrolled
    United States: 507
    Worldwide total number of subjects
    1457
    EEA total number of subjects
    361
    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)
    196
    From 65 to 84 years
    1123
    85 years and over
    138

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants who completed one of the feeder studies (Study H8A-MC-LZAM or H8A-MC-LZAN) were enrolled in this study.

    Pre-assignment
    Screening details
    		 No text entered

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Placebo administered intravenously every 4 weeks through Week 80.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo administered intravenously every 4 weeks through Week 80.

    Arm title
    		 Solanezumab
    Arm description
    		 400 mg administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Solanezumab
    Investigational medicinal product code
    Other name
    LY2062430
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    400 mg of Solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.

    Number of subjects in period 1
    		Placebo Solanezumab
    Started
    723
    734
    Received at Least 1 Dose of Study Drug
    723
    734
    Completed
    70
    61
    Not completed
    653
    673
         Adverse event, serious fatal
    40
    43
         Parent/Caregiver Decision
    246
    228
         Physician decision
    60
    45
         Consent withdrawn by subject
    57
    72
         Adverse event, non-fatal
    74
    73
         Sponsor Decision
    163
    195
         Lost to follow-up
    4
    -
         Abnormal Lab/ECG Result
    -
    1
         Protocol deviation
    8
    16
         Not treated
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo administered intravenously every 4 weeks through Week 80.

    Reporting group title
    Solanezumab
    Reporting group description
    		 400 mg administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.

    Reporting group values
    		 Placebo Solanezumab Total
    Number of subjects
    		 723 734 1457
    Age categorical
    Units: Subjects
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 73.10 ( 8.004 ) 72.96 ( 7.766 ) -
    Gender categorical
    Units: Subjects
        Female
    		 406 415 821
        Male
    		 317 319 636
    Sex: Female, Male
    Units: Subjects
        Female
    		 406 415 821
        Male
    		 317 319 636
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 137 149 286
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 13 16 29
        White
    		 571 566 1137
        More than one race
    		 2 3 5
        Unknown or Not Reported
    		 0 0 0
    Region of Enrollment
    Units: Subjects
        Argentina
    		 41 40 81
        United States
    		 264 243 507
        Japan
    		 69 87 156
        United Kingdom
    		 17 18 35
        Spain
    		 15 22 37
        Russia
    		 13 15 28
        Canada
    		 38 40 78
        South Korea
    		 33 32 65
        Sweden
    		 21 15 36
        Taiwan
    		 26 23 49
        Poland
    		 18 25 43
        Brazil
    		 38 34 72
        Italy
    		 41 45 86
        Australia
    		 30 30 60
        France
    		 22 23 45
        Germany
    		 37 42 79

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo administered intravenously every 4 weeks through Week 80.

    Reporting group title
    Solanezumab
    Reporting group description
    		 400 mg administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.

    Primary: Assess the Number of Participants with One or More Drug-Related Adverse Events (AEs) or any Serious AEs (SAEs)

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    End point title
    		 Assess the Number of Participants with One or More Drug-Related Adverse Events (AEs) or any Serious AEs (SAEs) [1]
    End point description
    The number of participants with 1 or more AEs assessed as related to the study drug and is summarized cumulatively. In addition, the number of participants with 1 or more serious AEs is summarized cumulatively. A serious AE is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. Analysis Population Description: All randomized participants who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    Baseline through Week 104
    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: No arm comparison analyses were planned or conducted.
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    723
    734
    Units: participants
    number (not applicable)
        SAE
    308
    299
        Other AE
    485
    514
    No statistical analyses for this end point

    Secondary: Change from baseline to 104-week endpoint in Alzheimer's Disease Assessment Scale - Cognitive 14-Item Scale (ADAS-Cog14)

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    End point title
    		 Change from baseline to 104-week endpoint in Alzheimer's Disease Assessment Scale - Cognitive 14-Item Scale (ADAS-Cog14)
    End point description
    ADAS-Cog14 is ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity. Least Squares (LS) Mean was determined by mixed model repeated measures (MMRM) methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 Mini-Mental State Examination (MMSE) status (mild/moderate), concomitant acetylcholinesterase inhibitors (AChEI)/Memantine use at baseline (yes/no), baseline age and treatment*visit. Analysis Population Description: Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for ADAS-Cog14.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    409
    451
    Units: Units on a scale
        least squares mean (standard error)
    17.58 ( 0.532 )
    17.56 ( 0.517 )
    Statistical analysis title
    		 STATISTICAL_ANALYSIS_TITLE
    Comparison groups
    Solanezumab v Placebo
    Number of subjects included in analysis
    860
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    P-value
    		 = 0.974
    Method
    		 Mixed models analysis
    Parameter type
    		 Median difference (net)
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.14
         upper limit
    		 1.11
    Notes
    [2] - The noninferiority margin for this hypothesis was specified as 50% of the treatment difference observed at the end of the feeder study. If the lower limit of the confidence interval (CI) was greater than 0, the noninferiority criterion was met, indicating that at least 50% of the treatment difference observed at the end of the feeder studies was maintained at specified time points in the delayed-start period.

    Secondary: Change from baseline to 104-week endpoint in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL)

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    End point title
    		 Change from baseline to 104-week endpoint in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL)
    End point description
    ADCS-ADL is a 23-item inventory developed as a Rater-administered questionnaire answered by the participant’s caregiver. It measures performance of basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit. Analysis Population Description: Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for ADCS-ADL.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    420
    456
    Units: Units on a scale
        least squares mean (standard error)
    -26.77 ( 0.888 )
    -24.77 ( 0.871 )
    No statistical analyses for this end point

    Secondary: Change from baseline to 104-week endpoint in Clinical Dementia Rating - Sum of Boxes (CDR-SB)

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    End point title
    		 Change from baseline to 104-week endpoint in Clinical Dementia Rating - Sum of Boxes (CDR-SB)
    End point description
    CDR-SB is a semi-structured interview of participants and their caregivers. Participant’s cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit. Analysis Population Description: Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for CDR-SB.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    416
    452
    Units: Units on a scale
        least squares mean (standard error)
    5.59 ( 0.174 )
    5.27 ( 0.169 )
    No statistical analyses for this end point

    Secondary: Change from baseline to 104-week endpoint in Neuropsychiatric Inventory (NPI)

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    End point title
    		 Change from baseline to 104-week endpoint in Neuropsychiatric Inventory (NPI)
    End point description
    The NPI is a questionnaire administered to caregivers that quantifies behavioral changes in dementia. Each of the 12 behavioral domains the caregiver reports as present are scored for Frequency, scale: 1 (Occasionally) to 4 (Very Frequently), and Severity, scale: 1 (Mild) to 3 (Severe). If the domain is reported by the caregiver as 'Not Affected,' that domain is scored as 0. The individual domain scores are calculated by multiplying the frequency times the severity for each domain. NPI Total Score is calculated by adding the individual domain scores together for all 12 domains, with a scores range from 0 to 144. Lower scores indicated less severity and higher scores indicated a greater severity of neuropsychiatric disturbance. LS Mean was determined by MMRM methodology. APD: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for NPI.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    414
    457
    Units: Units on a scale
    least squares mean (standard error)
        Mild Alzheimer’s Disease
    4.49 ( 0.788 )
    5.41 ( 0.773 )
        Moderate Alzheimer’s Disease
    11.90 ( 1.517 )
    8.10 ( 1.427 )
    No statistical analyses for this end point

    Secondary: Change from baseline to 104-week endpoint in Resource Utilization in Dementia - Lite (RUD-Lite) Caregiver Hours

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    End point title
    		 Change from baseline to 104-week endpoint in Resource Utilization in Dementia - Lite (RUD-Lite) Caregiver Hours
    End point description
    The RUD-Lite is a caregiver-completed assessment designed to assess the amount of formal and informal resources used by participants and the primary caregiver. It is completed by the caregiver and compiles data on the following resources: length of time the caregiver spends giving care, assisting participants with basic activities of daily living (BADL: eating dressing, grooming, bathing); assisting participants with instrumental activities of daily living (IADLs: shopping, cooking, housekeeping, laundry, transportation, taking medication, managing finances), and providing supervision. Scores range from 0 to 24 hours. Higher values indicate greater resource use. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit. APD: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline observation for RUD-Lite.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    415
    451
    Units: hours per day (hr/day)
    least squares mean (standard error)
        Mild Alzheimer’s Disease-Basic ADL
    1.96 ( 0.184 )
    1.21 ( 0.182 )
        Mild Alzheimer’s Disease-Instrumental ADL
    1.65 ( 0.207 )
    1.05 ( 0.205 )
        Mild Alzheimer’s Disease-Supervision
    2.84 ( 0.368 )
    2.59 ( 0.361 )
        Moderate Alzheimer’s Disease-Basic ADL
    3.19 ( 0.461 )
    3.54 ( 0.436 )
        Moderate Alzheimer’s Disease-Instrumental ADL
    1.75 ( 0.461 )
    1.72 ( 0.433 )
        Moderate Alzheimer’s Disease-Supervision
    5.03 ( 0.693 )
    4.47 ( 0.654 )
    No statistical analyses for this end point

    Secondary: Change from baseline to 104-week endpoint in EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy version (EQ-5D Proxy)

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    End point title
    		 Change from baseline to 104-week endpoint in EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy version (EQ-5D Proxy)
    End point description
    EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument assessing caregiver's impression of participants overall health state. Profile allows caregivers to rate participant's health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale: 1 (no problem), 2 (some problems), and 3 (major problems). These attribute combinations are converted into a weighted Health-State Index Score according to the United States (US) population-based algorithm. EQ-5D US Population-Based Index Scores range from -0.11 to 1.0. A score of 1.0 indicated perfect health. The Overall Health State Index Score is caregiver-reported using a visual analogue scale marked 0 (worst imaginable health) to 100 (best imaginable health state). LS Mean was determined by MMRM methodology. APD: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    414
    453
    Units: Units on a scale
    least squares mean (standard error)
        Mild Alzheimer’s Disease
    -0.07 ( 0.010 )
    -0.06 ( 0.009 )
        Moderate Alzheimer’s Disease
    -0.16 ( 0.020 )
    -0.16 ( 0.019 )
    No statistical analyses for this end point

    Secondary: Change from baseline to 104-week endpoint in Quality of Life in Alzheimer's Disease (QoL-AD)

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    End point title
    		 Change from baseline to 104-week endpoint in Quality of Life in Alzheimer's Disease (QoL-AD)
    End point description
    The QoL-AD (Caregiver Total Score) is a disease-specific measure of quality of life for an Alzheimer's Disease (AD) population administered to the participant's primary caregiver, who answers on behalf of the participant. The assessment consists of 13 items covering physical health, energy, mood, living situations, memory, family, marriage, friends, chores, fun, money, self and life as a whole. The assessment is scored on a 4-point Likert scale with scores ranging from 1 (poor) to 4 (excellent). QoL-AD Total Score is defined as the sum of the 13 items with a scores range from 13 to 52. Higher scores denote a better quality of life. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit. APD: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for QoL-AD.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    387
    413
    Units: Units on a scale
    least squares mean (standard error)
        QLAD Self-Report Total Score-Mild Alzheimer’s
    -1.37 ( 0.331 )
    -0.98 ( 0.327 )
        QLAD Caregiver Total Score-Mild Alzheimer’s
    -3.28 ( 0.350 )
    -3.63 ( 0.345 )
        QLAD Self-Report Total Score-Moderate Alzheimer’s
    -2.52 ( 0.605 )
    -2.34 ( 0.585 )
        QLAD Caregiver Total Score-Moderate Alzheimer’s
    -4.26 ( 0.573 )
    -3.14 ( 0.552 )
    No statistical analyses for this end point

    Secondary: Change from baseline to 104-week endpoint in Mini-Mental State Examination (MMSE)

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    End point title
    		 Change from baseline to 104-week endpoint in Mini-Mental State Examination (MMSE)
    End point description
    The MMSE is an instrument used to assess a participant's cognitive function. The instrument is divided into 2 sections. The first section measures orientation, memory, and attention with scores ranging from 0 to 21 (lower scores indicate greater impairment). The second section tests the ability of the participant to name objects, follow verbal and written commands, write a sentence, and copy figures with scores ranging from 0 to 9 (lower scores indicate greater impairment). The range for MMSE Total Score is 0 to 30. Lower scores indicate more impairment. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit. APD: Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for MMSE.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    412
    446
    Units: Units on a scale
        least squares mean (standard error)
    -8.08 ( 0.270 )
    -7.60 ( 0.263 )
    No statistical analyses for this end point

    Secondary: Change from baseline to 52-week endpoint in Plasma Amyloid Beta (Aβ) Levels

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    End point title
    		 Change from baseline to 52-week endpoint in Plasma Amyloid Beta (Aβ) Levels
    End point description
    Concentration of the peptide Aβ 1-40 and Aβ 1-42 in plasma measured by immunoassay. The immunoassays for plasma Aβ 1-40 and Aβ 1-42 peptides were modified to render them tolerant to the presence of Solanezumab which would otherwise interfere with non-modified assays. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit. APD: All Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for plasma Aβ 1-40 and Aβ 1-42.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    515
    532
    Units: picograms per milliliter (pg/mL)
    least squares mean (standard error)
        Aβ 1-40-Mild Alzheimer’s Disease
    176412.04 ( 3718.292 )
    173064.99 ( 3717.695 )
        Aβ 1-42-Mild Alzheimer’s Disease
    19854.92 ( 366.392 )
    19723.48 ( 368.644 )
        Aβ 1-40-Moderate Alzheimer’s Disease
    169356 ( 4627.8 )
    169087 ( 4511.6 )
        Aβ 1-42-Moderate Alzheimer’s Disease
    19237 ( 556.3 )
    19552 ( 528.7 )
    No statistical analyses for this end point

    Secondary: Change from baseline to 104-week endpoint in volumetric Magnetic Resonance Imaging (vMRI)

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    End point title
    		 Change from baseline to 104-week endpoint in volumetric Magnetic Resonance Imaging (vMRI)
    End point description
    The vMRI assessment of right and left hippocampal volume is reported. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit. APD: Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for vMRI.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    310
    325
    Units: Cubic millimeter (mm³)
    least squares mean (standard error)
        Right hippocampal volume-Mild Alzheimer’s Disease
    -230.23 ( 8.232 )
    -230.07 ( 8.195 )
        Left hippocampal volume-Mild Alzheimer’s Disease
    -257.15 ( 8.153 )
    -244.00 ( 8.115 )
        Right hippocampal volume-Moderate Alzheimer’s
    -261.39 ( 11.796 )
    -256.52 ( 11.246 )
        Left hippocampal volume-Moderate Alzheimer’s
    -255.16 ( 11.466 )
    -253.29 ( 10.858 )
    No statistical analyses for this end point

    Secondary: Change from baseline to 104-week endpoint in Alzheimer's Disease Assessment Scale - Cognitive Subscore 11-Item Scale (ADAS-Cog11)

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    End point title
    		 Change from baseline to 104-week endpoint in Alzheimer's Disease Assessment Scale - Cognitive Subscore 11-Item Scale (ADAS-Cog11)
    End point description
    The cognitive subscale of the ADAS (ADAS Cog11) was used as a primary efficacy measure and consists of 11 items assessing areas of function most typically impaired in Alzheimer’s disease: orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment*visit. APD: Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for ADAS-Cog11.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 104
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    375
    409
    Units: units on a scale
        least squares mean (standard error)
    17.78 ( 0.595 )
    17.38 ( 0.580 )
    No statistical analyses for this end point

    Secondary: Change from baseline to 80-week endpoint in Amyloid Plaque Burden in the Brain using Positron Emission Tomography (PET) Imaging

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    End point title
    		 Change from baseline to 80-week endpoint in Amyloid Plaque Burden in the Brain using Positron Emission Tomography (PET) Imaging
    End point description
    Amyloid plaques are dense, mostly insoluble clumps of protein fragments. They leave a highly damaging substance outside and around the brain’s nerve cells. People with Alzheimer's Disease have a buildup of these plaques in their hippocampus. changes in amyloid plaque burden will be determined using positron emission tomography (PET) imaging. APD: Feeder Intent-to-Treat Population: All randomized participants with mild Alzheimer's Disease from feeder studies, who received at least one dose of study drug and had baseline & at least one post baseline observation for Amyloid Plaque Burden.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 80
    End point values
    		 Placebo Solanezumab
    Number of subjects analysed
    42
    48
    Units: units on a scale
        arithmetic mean (standard deviation)
    0.00 ( 0.131 )
    -0.01 ( 0.222 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Entire Study
    Adverse event reporting additional description
    H8A-MC-LZAO
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Placebo: Solanezumab 400mg Open Label
    Reporting group description
    		 -

    Reporting group title
    Solanezumab 400mg: Solanezumab 400mg Open Label
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo: Solanezumab 400mg Open Label Solanezumab 400mg: Solanezumab 400mg Open Label
    Total subjects affected by serious adverse events
         subjects affected / exposed
    308 / 723 (42.60%)
    299 / 734 (40.74%)
         number of deaths (all causes)
    39
    43
         number of deaths resulting from adverse events
    4
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    adenocarcinoma of colon
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    basal cell carcinoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    benign soft tissue neoplasm
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bladder cancer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bladder cancer recurrent
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bladder transitional cell carcinoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    brain neoplasm
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast cancer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    breast cancer metastatic
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    chronic myeloid leukaemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colon cancer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colon cancer metastatic
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    essential thrombocythaemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric cancer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    granular cell tumour
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    invasive ductal breast carcinoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lung cancer metastatic
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    lung carcinoma cell type unspecified stage iv
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lung neoplasm malignant
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lymphoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    malignant melanoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malignant neoplasm of unknown primary site
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malignant neoplasm progression
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    metastases to liver
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    metastatic malignant melanoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neoplasm
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    non-small cell lung cancer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophageal adenocarcinoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancreatic carcinoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    pancreatic carcinoma metastatic
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancreatic neoplasm
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    papillary thyroid cancer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    plasma cell myeloma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    plasmacytoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    prostate cancer metastatic
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed [1]
    0 / 317 (0.00%)
    1 / 319 (0.31%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rectal cancer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    renal cell carcinoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    renal neoplasm
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    salivary gland neoplasm
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    squamous cell carcinoma of skin
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    uterine cancer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed [2]
    1 / 406 (0.25%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vascular disorders
    aortic aneurysm
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    aortic stenosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    arterial thrombosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    arteriosclerosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    deep vein thrombosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    6 / 734 (0.82%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haematoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypertensive crisis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypotension
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peripheral artery thrombosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peripheral ischaemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    shock
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thromboangiitis obliterans
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombophlebitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    venous thrombosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    cataract operation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    abasia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    adverse drug reaction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    asthenia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    5 / 723 (0.69%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    catheter site haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    chest pain
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    complication associated with device
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    death
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    4 / 723 (0.55%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 4
    0 / 1
    drowning
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    gait disturbance
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    general physical health deterioration
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    non-cardiac chest pain
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oedema peripheral
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pain
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sudden death
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    Social circumstances
    activities of daily living impaired
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    acquired hydrocele
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed [3]
    0 / 317 (0.00%)
    1 / 319 (0.31%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    acute pulmonary oedema
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    acute respiratory failure
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    aspiration
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    benign prostatic hyperplasia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed [4]
    2 / 317 (0.63%)
    1 / 319 (0.31%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bronchospasm
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cystocele
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed [5]
    1 / 406 (0.25%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dyspnoea
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypoxia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    interstitial lung disease
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    lung disorder
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nasal polyps
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    organising pneumonia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pharyngeal oedema
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pleural effusion
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    4 / 723 (0.55%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia aspiration
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    5 / 723 (0.69%)
    5 / 734 (0.68%)
         occurrences causally related to treatment / all
    0 / 5
    2 / 6
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    pneumothorax
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumothorax spontaneous
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    prostatomegaly
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed [6]
    0 / 317 (0.00%)
    1 / 319 (0.31%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    6 / 734 (0.82%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    respiratory distress
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    respiratory failure
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 3
         deaths causally related to treatment / all
    1 / 1
    0 / 2
    uterine prolapse
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed [7]
    1 / 406 (0.25%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    abnormal behaviour
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    affective disorder
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    aggression
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    agitation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    11 / 723 (1.52%)
    7 / 734 (0.95%)
         occurrences causally related to treatment / all
    1 / 11
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    alcohol abuse
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    behavioural and psychiatric symptoms of dementia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    7 / 723 (0.97%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 10
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bipolar disorder
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    completed suicide
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    confusional state
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    6 / 734 (0.82%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    delirium
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    5 / 723 (0.69%)
    5 / 734 (0.68%)
         occurrences causally related to treatment / all
    0 / 5
    1 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    delirium febrile
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    delusion
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    delusional perception
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    disorientation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    insomnia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    irritability
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    major depression
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mental status changes
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    5 / 723 (0.69%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    restlessness
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    suicidal behaviour
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    suicidal ideation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    suicide attempt
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    blood pressure increased
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic enzyme increased
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    acetabulum fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ankle fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bone contusion
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cervical vertebral fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    clavicle fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    concussion
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    contusion
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    craniocerebral injury
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    facial bones fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fall
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    27 / 723 (3.73%)
    23 / 734 (3.13%)
         occurrences causally related to treatment / all
    0 / 27
    0 / 25
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    femoral neck fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    4 / 723 (0.55%)
    13 / 734 (1.77%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    femur fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    11 / 723 (1.52%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    1 / 11
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fibula fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    flail chest
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    foot fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    forearm fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fractured ischium
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    head injury
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hip fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    8 / 723 (1.11%)
    11 / 734 (1.50%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    humerus fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    4 / 723 (0.55%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    incisional hernia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    injury
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    joint dislocation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    joint injury
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    laceration
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ligament sprain
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lumbar vertebral fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    patella fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pelvic fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    4 / 734 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    periprosthetic fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pubis fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary contusion
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    radius fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rib fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    road traffic accident
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    skull fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spinal column injury
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spinal compression fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spinal fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    subdural haematoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    4 / 723 (0.55%)
    5 / 734 (0.68%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    subdural haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tibia fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    traumatic haematoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    traumatic intracranial haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    upper limb fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    wound
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    wound dehiscence
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    wrist fracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    acute myocardial infarction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    4 / 723 (0.55%)
    4 / 734 (0.54%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    angina pectoris
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    4 / 734 (0.54%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    arrhythmia supraventricular
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    atrial fibrillation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    5 / 723 (0.69%)
    9 / 734 (1.23%)
         occurrences causally related to treatment / all
    1 / 5
    6 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    atrial flutter
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    atrioventricular block
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    atrioventricular block second degree
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bradycardia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cardiac arrest
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    5 / 723 (0.69%)
    5 / 734 (0.68%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 5
    0 / 4
    cardiac failure
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    cardiac failure acute
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    cardiac failure congestive
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    6 / 723 (0.83%)
    5 / 734 (0.68%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    cardiac perforation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cardio-respiratory arrest
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    cardiogenic shock
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    cardiomyopathy
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    cardiopulmonary failure
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    cardiovascular disorder
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    coronary artery stenosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    myocardial infarction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    5 / 723 (0.69%)
    4 / 734 (0.54%)
         occurrences causally related to treatment / all
    2 / 5
    1 / 4
         deaths causally related to treatment / all
    1 / 1
    1 / 3
    palpitations
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pericardial effusion
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sinus bradycardia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sinus node dysfunction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    4 / 723 (0.55%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tachycardia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ventricular extrasystoles
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    altered state of consciousness
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    brain stem haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    brain stem infarction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebral haematoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebral haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    cerebral infarction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    4 / 734 (0.54%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebral microhaemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebrospinal fluid leakage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cerebrovascular accident
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    1 / 1
    0 / 1
    circadian rhythm sleep disorder
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cognitive disorder
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    coma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    complex partial seizures
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dementia alzheimer's type
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    8 / 723 (1.11%)
    5 / 734 (0.68%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    dementia with lewy bodies
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    depressed level of consciousness
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dizziness
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    encephalopathy
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    epilepsy
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    generalised tonic-clonic seizure
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemorrhage intracranial
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemorrhagic cerebral infarction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemorrhagic stroke
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    headache
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hemiparesis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypoxic-ischaemic encephalopathy
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intracranial aneurysm
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intraventricular haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    ischaemic cerebral infarction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ischaemic stroke
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    6 / 723 (0.83%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    lethargy
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    loss of consciousness
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    metabolic encephalopathy
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    myoclonus
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    normal pressure hydrocephalus
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    presyncope
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    seizure
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    11 / 734 (1.50%)
         occurrences causally related to treatment / all
    0 / 3
    3 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    somnolence
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    subarachnoid haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    syncope
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    10 / 723 (1.38%)
    15 / 734 (2.04%)
         occurrences causally related to treatment / all
    1 / 10
    1 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tremor
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vasogenic cerebral oedema
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    anaemia folate deficiency
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    coagulopathy
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    normochromic normocytic anaemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    vertigo
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    cataract
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    glaucoma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    retinal detachment
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    strabismus
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vitreous haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal hernia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    abdominal pain
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    abdominal pain upper
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colitis ischaemic
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colonic fistula
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colonic pseudo-obstruction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    constipation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diarrhoea
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    4 / 723 (0.55%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diarrhoea haemorrhagic
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diverticular fistula
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diverticulum
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    duodenal ulcer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dyspepsia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dysphagia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    erosive oesophagitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    faecaloma
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric ulcer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric ulcer haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastritis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrooesophageal reflux disease
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haematochezia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haemorrhoids
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hiatus hernia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ileus
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ileus paralytic
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    inguinal hernia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    4 / 734 (0.54%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intestinal obstruction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    jejunal perforation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    large intestine polyp
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lower gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophageal perforation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophageal ulcer haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancreatitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    5 / 723 (0.69%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancreatitis acute
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peptic ulcer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rectal prolapse
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rectal ulcer haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    small intestinal obstruction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    small intestinal perforation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    subileus
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    upper gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    bile duct obstruction
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bile duct stone
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholangitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholecystitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholecystitis acute
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholelithiasis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    drug-induced liver injury
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gallbladder polyp
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic steatosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    dermatitis contact
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diabetic foot
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    drug eruption
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypersensitivity vasculitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sebaceous gland disorder
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urticaria
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    acute kidney injury
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    6 / 723 (0.83%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    acute prerenal failure
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bladder tamponade
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    calculus bladder
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haematuria
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    hydronephrosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nephrolithiasis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    renal failure
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary bladder haemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary retention
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    myxoedema
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    arthritis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    arthropathy
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    back pain
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cervical spinal stenosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dupuytren's contracture
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    foot deformity
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gouty arthritis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intervertebral disc protrusion
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    joint effusion
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    joint swelling
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lumbar spinal stenosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    muscle spasms
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    muscular weakness
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    osteoarthritis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    7 / 723 (0.97%)
    13 / 734 (1.77%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    osteolysis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rhabdomyolysis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    rotator cuff syndrome
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spinal column stenosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    spondylolisthesis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    abdominal abscess
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    appendicitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    arthritis bacterial
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bacteraemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bacterial infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bronchitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    5 / 734 (0.68%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    campylobacter gastroenteritis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    7 / 734 (0.95%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    clostridium difficile colitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    clostridium difficile infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colostomy infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cystitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    device related infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diverticulitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    4 / 723 (0.55%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    erysipelas
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    escherichia sepsis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    escherichia urinary tract infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    extradural abscess
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastroenteritis viral
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    3 / 734 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    groin abscess
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    herpes simplex encephalitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    herpes zoster
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infected skin ulcer
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    influenza
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    4 / 734 (0.54%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    labyrinthitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lower respiratory tract infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lung infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    mediastinitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    meningitis bacterial
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    orchitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed [8]
    0 / 317 (0.00%)
    1 / 319 (0.31%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pericarditis tuberculous
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pharyngitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    27 / 723 (3.73%)
    27 / 734 (3.68%)
         occurrences causally related to treatment / all
    1 / 31
    1 / 31
         deaths causally related to treatment / all
    0 / 3
    0 / 1
    pneumonia bacterial
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia pneumococcal
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    post procedural infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    postoperative wound infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pulmonary sepsis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    pulmonary tuberculosis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    respiratory tract infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    6 / 734 (0.82%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    septic shock
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    2 / 723 (0.28%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    sinusitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tooth abscess
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    upper respiratory tract infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    16 / 723 (2.21%)
    17 / 734 (2.32%)
         occurrences causally related to treatment / all
    1 / 21
    1 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary tract infection bacterial
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary tract infection staphylococcal
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urosepsis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    5 / 734 (0.68%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    viral infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    wound infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    adult failure to thrive
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    decreased appetite
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    3 / 723 (0.41%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dehydration
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    7 / 723 (0.97%)
    13 / 734 (1.77%)
         occurrences causally related to treatment / all
    0 / 7
    1 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diabetes mellitus
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    failure to thrive
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    gout
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperammonaemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperglycaemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperkalaemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypernatraemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperosmolar hyperglycaemic state
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypoglycaemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    4 / 723 (0.55%)
    0 / 734 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyponatraemia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypophagia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malnutrition
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    1 / 723 (0.14%)
    2 / 734 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    type 2 diabetes mellitus
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    0 / 723 (0.00%)
    1 / 734 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
    [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
    [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
    [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo: Solanezumab 400mg Open Label Solanezumab 400mg: Solanezumab 400mg Open Label
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    485 / 723 (67.08%)
    514 / 734 (70.03%)
    Investigations
    weight decreased
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    48 / 723 (6.64%)
    38 / 734 (5.18%)
         occurrences all number
    51
    40
    Injury, poisoning and procedural complications
    contusion
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    45 / 723 (6.22%)
    58 / 734 (7.90%)
         occurrences all number
    62
    84
    fall
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    145 / 723 (20.06%)
    136 / 734 (18.53%)
         occurrences all number
    222
    245
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    42 / 723 (5.81%)
    36 / 734 (4.90%)
         occurrences all number
    43
    38
    Nervous system disorders
    cerebral microhaemorrhage
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    42 / 723 (5.81%)
    56 / 734 (7.63%)
         occurrences all number
    47
    61
    dizziness
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    39 / 723 (5.39%)
    43 / 734 (5.86%)
         occurrences all number
    43
    53
    headache
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    49 / 723 (6.78%)
    46 / 734 (6.27%)
         occurrences all number
    65
    64
    General disorders and administration site conditions
    oedema peripheral
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    31 / 723 (4.29%)
    37 / 734 (5.04%)
         occurrences all number
    33
    38
    Gastrointestinal disorders
    constipation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    51 / 723 (7.05%)
    64 / 734 (8.72%)
         occurrences all number
    56
    71
    diarrhoea
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    58 / 723 (8.02%)
    76 / 734 (10.35%)
         occurrences all number
    72
    105
    vomiting
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    41 / 723 (5.67%)
    51 / 734 (6.95%)
         occurrences all number
    51
    70
    Respiratory, thoracic and mediastinal disorders
    benign prostatic hyperplasia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed [9]
    17 / 317 (5.36%)
    9 / 319 (2.82%)
         occurrences all number
    17
    10
    cough
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    50 / 723 (6.92%)
    66 / 734 (8.99%)
         occurrences all number
    61
    74
    Psychiatric disorders
    agitation
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    75 / 723 (10.37%)
    64 / 734 (8.72%)
         occurrences all number
    83
    72
    anxiety
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    56 / 723 (7.75%)
    86 / 734 (11.72%)
         occurrences all number
    78
    114
    insomnia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    67 / 723 (9.27%)
    74 / 734 (10.08%)
         occurrences all number
    70
    80
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    42 / 723 (5.81%)
    33 / 734 (4.50%)
         occurrences all number
    51
    40
    back pain
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    49 / 723 (6.78%)
    67 / 734 (9.13%)
         occurrences all number
    54
    75
    Infections and infestations
    bronchitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    32 / 723 (4.43%)
    43 / 734 (5.86%)
         occurrences all number
    47
    56
    nasopharyngitis
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    78 / 723 (10.79%)
    88 / 734 (11.99%)
         occurrences all number
    129
    145
    upper respiratory tract infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    59 / 723 (8.16%)
    47 / 734 (6.40%)
         occurrences all number
    73
    61
    urinary tract infection
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    98 / 723 (13.55%)
    84 / 734 (11.44%)
         occurrences all number
    153
    161
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 19.0
         subjects affected / exposed
    35 / 723 (4.84%)
    37 / 734 (5.04%)
         occurrences all number
    39
    44
    Notes
    [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Nov 2012
    Amendment (c): Amended to specify the mild AD population as the primary population. In addition, all analyses were to be conducted in the moderate and overall (mild to moderate) populations. Finally, the duration of Study LZAO was extended for up to an additional 24 months or until solanezumab becomes commercially available in the host country, whichever occurs first.
    16 Sep 2014
    Amendment (d): Amended to extend the study for up to an additional 24 months or until solanezumab becomes commercially available in the host country, whichever occurs first. Additional secondary objectives and text were added to describe additional analyses to be performed with data from Study Periods 2 and 3.

    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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