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    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled and Delayed-Start Study of LY3314814 in Mild Alzheimer’s Disease Dementia (The DAYBREAK Study)

    Summary
    EudraCT number
    		 2015-005625-39
    Trial protocol
    		 GB   PT   ES   PL   CZ   DK   NL   FR   IT  
    Global end of trial date
    28 Sep 2018

    Results information
    Results version number
    		 v2(current)
    This version publication date
    15 Aug 2019
    First version publication date
    27 Jun 2019
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Correction of full data set

    Trial information

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    Trial identification
    Sponsor protocol code
    I8D-MC-AZET
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02783573
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 16024
    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,
    Sponsor organisation name
    AstraZeneca UK Limited
    Sponsor organisation address
    Charter Way, Macclesfield, Cheshire, United Kingdom, SK10 2NA
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, AstraZeneca UK Limited, 44 1625-58-2828,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, AstraZeneca UK Limited, 44 1625-58-2828,
    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
    28 Sep 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Sep 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main purpose of this study is to evaluate the efficacy of the study drug known as lanabecestat in participants with mild Alzheimer's disease (AD) dementia.
    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
    01 Jul 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Czech Republic: 129
    Country: Number of subjects enrolled
    United States: 600
    Country: Number of subjects enrolled
    Japan: 119
    Country: Number of subjects enrolled
    United Kingdom: 68
    Country: Number of subjects enrolled
    Portugal: 24
    Country: Number of subjects enrolled
    Russian Federation: 100
    Country: Number of subjects enrolled
    Spain: 78
    Country: Number of subjects enrolled
    Canada: 96
    Country: Number of subjects enrolled
    Korea, Republic of: 59
    Country: Number of subjects enrolled
    Netherlands: 30
    Country: Number of subjects enrolled
    China: 2
    Country: Number of subjects enrolled
    Taiwan: 24
    Country: Number of subjects enrolled
    Poland: 122
    Country: Number of subjects enrolled
    Denmark: 23
    Country: Number of subjects enrolled
    Italy: 66
    Country: Number of subjects enrolled
    Mexico: 29
    Country: Number of subjects enrolled
    France: 93
    Country: Number of subjects enrolled
    Germany: 60
    Worldwide total number of subjects
    1722
    EEA total number of subjects
    693
    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)
    257
    From 65 to 84 years
    1435
    85 years and over
    30

    Subject disposition

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    Recruitment
    Recruitment details
    		 No Text Available

    Pre-assignment
    Screening details
    		 In Period 1, per the protocol, placebo-controlled groups (Placebo for 78 weeks then Lanabecestat 20 mg; Placebo for 78 weeks then Lanabecestat 50 mg) were combined to form one placebo group. As study terminated early and very few participants entered into the period 2, the arms in period 2 are combined based on dose exposure for ease of comparison.

    Period 1
    Period 1 title
    Placebo-Controlled Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received placebo film-coated oral tablets once daily.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Film-coated tablets of placebo administered orally once a day.

    Arm title
    		 Lanabecestat 20 mg
    Arm description
    		 Participants received lanabecestat 20 mg film-coated oral tablets once daily.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lanabecestat
    Investigational medicinal product code
    Other name
    LY3314814, AZD3293
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    20 mg film-coated tablets of lanabecestat administered orally once a day.

    Arm title
    		 Lanabecestat 50 mg
    Arm description
    		 Participants received lanabecestat 50 mg film-coated oral tablets once daily.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lanabecestat
    Investigational medicinal product code
    Other name
    LY3314814, AZD3293
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg film-coated tablets of lanabecestat administered orally once a day.

    Number of subjects in period 1
    		Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Started
    562
    590
    570
    Received at Least 1 Dose of Study Drug
    558
    588
    568
    Completed
    26
    28
    22
    Not completed
    536
    562
    548
         Adverse event, serious fatal
    4
    2
    3
         Physician decision
    3
    1
    3
         Consent withdrawn by subject
    15
    20
    23
         Non-Compliance
    -
    1
    -
         Adverse event, non-fatal
    13
    17
    13
         Withdrawal due to Caregiver Circumstance
    3
    3
    9
         Other-selected by Investigator
    -
    1
    2
         Sponsor Decision
    494
    512
    492
         Lost to follow-up
    3
    3
    1
         Protocol deviation
    1
    2
    -
         Lack of efficacy
    -
    -
    2
    Period 2
    Period 2 title
    Delayed-Start Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Lanabecestat 20 mg
    Arm description
    		 Participants received lanabecestat 20 mg film-coated oral tablets once daily.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lanabecestat
    Investigational medicinal product code
    Other name
    LY3314814, AZD3293
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    20 mg film-coated tablets of lanabecestat administered orally.

    Arm title
    		 Lanabecestat 50 mg
    Arm description
    		 Participants received lanabecestat 50 mg film-coated oral tablets once daily.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lanabecestat
    Investigational medicinal product code
    Other name
    LY3314814, AZD3293
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg film-coated tablets of lanabecestat administered orally.

    Number of subjects in period 2 [1]
    		Lanabecestat 20 mg Lanabecestat 50 mg
    Started
    17
    12
    Received at Least 1 Dose of Study Drug
    14
    12
    Completed
    0
    0
    Not completed
    17
    12
         Sponsor Decision
    17
    12
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Patients who completed period 1 may not have entered period 2 due to early termination of the study.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo film-coated oral tablets once daily.

    Reporting group title
    Lanabecestat 20 mg
    Reporting group description
    		 Participants received lanabecestat 20 mg film-coated oral tablets once daily.

    Reporting group title
    Lanabecestat 50 mg
    Reporting group description
    		 Participants received lanabecestat 50 mg film-coated oral tablets once daily.

    Reporting group values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg Total
    Number of subjects
    		 562 590 570 1722
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 72.1 ± 7.1 72.3 ± 7.0 72.6 ± 7.0 -
    Gender categorical
    Units: Subjects
        Female
    		 348 335 340 1023
        Male
    		 214 255 230 699
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 53 45 55 153
        Not Hispanic or Latino
    		 416 442 423 1281
        Unknown or Not Reported
    		 93 103 92 288
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 5 7 6 18
        Asian
    		 64 76 69 209
        Native Hawaiian or Other Pacific Islander
    		 0 1 3 4
        Black or African American
    		 4 5 9 18
        White
    		 387 398 389 1174
        More than one race
    		 72 70 62 204
        Unknown or Not Reported
    		 30 33 32 95
    Region of Enrollment
    Units: Subjects
        United States
    		 196 205 199 600
        Japan
    		 38 43 38 119
        United Kingdom
    		 23 22 23 68
        Portugal
    		 8 8 8 24
        Russia
    		 33 36 31 100
        Spain
    		 25 25 28 78
        Canada
    		 32 33 31 96
        South Korea
    		 19 20 20 59
        Netherlands
    		 9 9 12 30
        China
    		 1 0 1 2
        Taiwan
    		 5 10 9 24
        Poland
    		 39 43 40 122
        Denmark
    		 7 8 8 23
        Italy
    		 23 22 21 66
        Mexico
    		 11 9 9 29
        France
    		 30 33 30 93
        Germany
    		 21 22 17 60
        Czech Republic
    		 42 42 45 129
    ADAS-Cog13 (13-item Alzheimer’s Disease Assessment Scale)
    ADAS-Cog13, a 13-item rating scale, measured the severity of cognitive dysfunction in persons with Alzheimer's disease (AD). Scores ranged from 0 to 85, with a higher score indicating worse cognitive functioning.
    Units: Units on a Scale
        arithmetic mean (standard deviation)
    		 30.4 ± 7.9 30.6 ± 8.3 30.6 ± 8.5 -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo film-coated oral tablets once daily.

    Reporting group title
    Lanabecestat 20 mg
    Reporting group description
    		 Participants received lanabecestat 20 mg film-coated oral tablets once daily.

    Reporting group title
    Lanabecestat 50 mg
    Reporting group description
    		 Participants received lanabecestat 50 mg film-coated oral tablets once daily.
    Reporting group title
    Lanabecestat 20 mg
    Reporting group description
    		 Participants received lanabecestat 20 mg film-coated oral tablets once daily.

    Reporting group title
    Lanabecestat 50 mg
    Reporting group description
    		 Participants received lanabecestat 50 mg film-coated oral tablets once daily.

    Subject analysis set title
    Lanabecestat
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received Lanabecestat film-coated tablets orally.

    Primary: Change from Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog13) Score

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    End point title
    		 Change from Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog13) Score
    End point description
    ADAS-Cog13 is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment-by-visit interaction, AChEI (acetylcholinesterase Inhibitor) use at baseline, pooled site, and covariates for baseline ADAS-Cog13 total score, age at baseline, and baseline ADAS-Cog13 total score-by-visit interaction. Analysis Population Description (APD): All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADAS-Cog13 measure.
    End point type
    Primary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    460
    471
    464
    Units: Units on a scale
        least squares mean (standard error)
    6.42 ± 1.23
    8.93 ± 1.11
    6.20 ± 1.32
    Statistical analysis title
    		 ADAS-Cog13
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    931
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.129
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    2.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.752
         upper limit
    		 5.776
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.64
    Statistical analysis title
    		 ADAS-Cog13
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    924
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.903
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -0.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.725
         upper limit
    		 3.296
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.76

    Secondary: Change from Baseline in Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items Score (ADCS-iADL)

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    End point title
    		 Change from Baseline in Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items Score (ADCS-iADL)
    End point description
    The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean was determined by MMRM model with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline iADL score, age at baseline, and baseline iADL score-by-visit interaction. APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADCS-iADL measure.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    357
    369
    347
    Units: Units on a scale
        least squares mean (standard error)
    -3.95 ± 1.27
    -6.91 ± 1.29
    -7.13 ± 1.40
    Statistical analysis title
    		 ADCS-iADL
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    726
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -2.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.488
         upper limit
    		 0.58
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.78
    Statistical analysis title
    		 ADCS-iADL
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    704
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.092
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -3.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.876
         upper limit
    		 0.525
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.86

    Secondary: Change from Baseline in Functional Activities Questionnaire (FAQ) Score

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    End point title
    		 Change from Baseline in Functional Activities Questionnaire (FAQ) Score
    End point description
    FAQ is a 10-item, caregiver-based questionnaire and was administered to the study partner who was asked to rate the participant's ability to perform a variety of activities ranging from writing checks, assembling tax records, shopping, playing games, food preparation, traveling, keeping appointments, traveling out of neighborhood, keeping track of current events and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. Each activity is rated on a scale from 0 to 3 (Never did and would have difficulty now=1; never did [the activity] but could do now =0; normal =0; has difficulty but does by self =1; requires assistance= 2; Dependent = 3). The maximum FAQ total score is 30, with higher scores indicating greater impairment. LS Mean determined by MMRM model. APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for FAQ score.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    358
    369
    347
    Units: Units on a scale
        least squares mean (standard error)
    3.93 ± 0.81
    5.16 ± 0.85
    3.41 ± 0.91
    Statistical analysis title
    		 FAQ Score
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    727
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.285
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    1.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.045
         upper limit
    		 3.499
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.14
    Statistical analysis title
    		 FAQ Score
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    705
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.661
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.889
         upper limit
    		 1.843
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.19

    Secondary: Change from Baseline on the Integrated Alzheimer’s Disease Rating Scale (iADRS) Score

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    End point title
    		 Change from Baseline on the Integrated Alzheimer’s Disease Rating Scale (iADRS) Score
    End point description
    The iADRS is a composite that measures both cognition and function. The iADRS comprises scores form the ADAS- Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 (score range 0 to 85 with higher scores reflecting worse performance) and the ADCS-iADL (score range from 0-59 with higher scores reflecting better performance). The iADRS score ranges from 0 to 144 with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline iADRS13 total score, age at baseline, and baseline iADRS13 total score-by-visit interaction. APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for iADRS.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    342
    348
    333
    Units: Units on a scale
        least squares mean (standard error)
    -10.46 ± 1.97
    -15.22 ± 1.90
    -12.43 ± 2.08
    Statistical analysis title
    		 iADRS
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    690
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.079
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -4.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.103
         upper limit
    		 0.56
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.69
    Statistical analysis title
    		 iADRS
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    675
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.486
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -1.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.573
         upper limit
    		 3.62
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.82

    Secondary: Change from Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score

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    End point title
    		 Change from Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score
    End point description
    The CDR-SB is a rater administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which no dementia = 0, questionable dementia = 0.5, mild dementia = 1, moderate dementia = 2 and severe dementia = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18, with higher scores indicating greater impairment. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline CDR-SB score, age at baseline, and baseline CDR-SB score-by-visit interaction. APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CDR-SB.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    369
    370
    363
    Units: Units on a scale
        least squares mean (standard error)
    2.32 ± 0.42
    2.57 ± 0.41
    2.10 ± 0.45
    Statistical analysis title
    		 CDR-SB
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    739
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.663
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    0.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.89
         upper limit
    		 1.391
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.57
    Statistical analysis title
    		 CDR-SB
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    732
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.717
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -0.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.423
         upper limit
    		 0.983
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.6

    Secondary: Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score Stage

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    End point title
    		 Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score Stage
    End point description
    The CDR global score is a composite score calculated using the Washington University CDR-assignment algorithm applied to the 6 individual domain box scores (Morris 1993). The memory domain is considered the primary category that drives the CDR global outcome, and all other domains are secondary. The CDR global score ranges from 0 to 3 (0 = no dementia, 0.5 = questionable dementia, 1 = mild dementia, 2 = moderate dementia, 3 = severe dementia). APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CDR global score.
    End point type
    Secondary
    End point timeframe
    From Loss of 1 Global Stage through Week 78
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    479
    500
    466
    Units: Days
        median (confidence interval 95%)
    379 (367 to 546)
    367 (365 to 456)
    449 (365 to 491)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Neuropsychiatric Inventory (NPI) Score

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    End point title
    		 Change from Baseline in Neuropsychiatric Inventory (NPI) Score
    End point description
    The NPI is a questionnaire administered to caregivers that quantifies behavioral changes. 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, with higher scores indicating a greater severity of neuropsychiatric disturbance. LS Mean was determined by MMRM methodology. All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for NPI.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    351
    363
    342
    Units: Units on a scale
        least squares mean (standard error)
    3.45 ± 1.70
    3.75 ± 1.84
    0.44 ± 1.45
    Statistical analysis title
    		 NPI
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    714
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.899
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.297
         upper limit
    		 4.889
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.34
    Statistical analysis title
    		 NPI
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    693
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.164
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -3.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.267
         upper limit
    		 1.238
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.16

    Secondary: Change from Baseline on the Mini-Mental State Examination (MMSE)

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    End point title
    		 Change from Baseline on the Mini-Mental State Examination (MMSE)
    End point description
    The MMSE is an instrument used to assess a participant's global cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline MMSE total score, age at baseline, and baseline MMSE total score-by-visit interaction. APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for MMSE.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    476
    495
    477
    Units: Units on a scale
        least squares mean (standard error)
    -4.16 ± 0.59
    -5.43 ± 0.58
    -4.31 ± 0.64
    Statistical analysis title
    		 MMSE
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    971
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.126
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -1.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.891
         upper limit
    		 0.362
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.82
    Statistical analysis title
    		 MMSE
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    953
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.862
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.867
         upper limit
    		 1.566
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.86

    Secondary: Percent Change from Baseline in Concentration of Cerebrospinal fluid (CSF) Biomarker Aβ1-42

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    End point title
    		 Percent Change from Baseline in Concentration of Cerebrospinal fluid (CSF) Biomarker Aβ1-42
    End point description
    Concentration of the peptide Aβ 1-42 in plasma measured by validated immunoassay. LS Mean was determined by Analysis of covariance (ANCOVA) with LOCF (last observation carried forward), terms for treatment, baseline biomarker and age at baseline. APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for Aβ1-42.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 71
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    4
    5
    5
    Units: Percentage change in Aβ1-42
        least squares mean (standard error)
    23.68 ± 26.76
    -13.87 ± 24.30
    -17.04 ± 23.26
    Statistical analysis title
    		 Aβ1-42
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    9
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.343
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -37.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -122.35
         upper limit
    		 47.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    37.49
    Statistical analysis title
    		 Aβ1-42
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    9
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.276
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -40.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -120.17
         upper limit
    		 38.73
    Variability estimate
    Standard error of the mean
    Dispersion value
    35.12

    Secondary: Percent Change from Baseline in Concentration of CSF Biomarker Aβ1-40

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    End point title
    		 Percent Change from Baseline in Concentration of CSF Biomarker Aβ1-40
    End point description
    Concentration of the peptide Aβ 1-40 in plasma measured by immunoassay. LS Mean was determined by ANCOVA with LOCF (last observation carried forward), terms for treatment, baseline biomarker and age at baseline. APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for Aβ1-40.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 71
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    4
    5
    5
    Units: Percentage change in Aβ1-40
        least squares mean (standard error)
    24.52 ± 23.08
    -37.42 ± 20.76
    -9.63 ± 20.74
    Statistical analysis title
    		 Aβ1-40
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    9
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.079
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -61.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -132.75
         upper limit
    		 8.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    31.3
    Statistical analysis title
    		 Aβ1-40
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    9
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.303
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -34.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -104.88
         upper limit
    		 36.59
    Variability estimate
    Standard error of the mean
    Dispersion value
    31.27

    Secondary: Change from Baseline in CSF Biomarker Total Tau

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    End point title
    		 Change from Baseline in CSF Biomarker Total Tau
    End point description
    Cerebrospinal fluid samples were collected for analysis of concentration total tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline biomarker and age at baseline. APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CSF Total Tau.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 71
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    4
    5
    5
    Units: Picogram per milliliter (pg/mL)
        least squares mean (standard error)
    1.84 ± 9.75
    18.16 ± 9.77
    -11.21 ± 9.32
    Statistical analysis title
    		 CSF Total Tau
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    9
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.283
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    16.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.015
         upper limit
    		 48.659
    Variability estimate
    Standard error of the mean
    Dispersion value
    14.29
    Statistical analysis title
    		 CSF Total Tau
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    9
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.349
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -13.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -42.929
         upper limit
    		 16.82
    Variability estimate
    Standard error of the mean
    Dispersion value
    13.21

    Secondary: Change from Baseline in CSF Biomarker Phosphorylated Tau

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    End point title
    		 Change from Baseline in CSF Biomarker Phosphorylated Tau
    End point description
    Cerebrospinal fluid samples are collected for analysis of concentration of phosphorylated tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline biomarker and age at baseline. APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CSF Phosphorylated Tau.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 71
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    4
    5
    5
    Units: Picogram per milliliter (pg/mL)
        least squares mean (standard error)
    2.22 ± 1.54
    3.81 ± 1.49
    0.08 ± 1.41
    Statistical analysis title
    		 CSF Phosphorylated Tau
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    9
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.494
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    1.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.457
         upper limit
    		 6.64
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.23
    Statistical analysis title
    		 CSF Phosphorylated Tau
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    9
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.323
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -2.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.743
         upper limit
    		 2.481
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.04

    Secondary: Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) Scan

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    End point title
    		 Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) Scan
    End point description
    Amyloid deposition in the brain is one of the defining neuropathologic findings of Alzheimer's disease. Florbetapir exhibits high affinity specific binding to amyloid plaques. The change from baseline was measured as average standard uptake value ratio in prespecified regions of interest assessed by florbetapir amyloid PET imaging in a subset of participants. The Centiloid standardizes quantitative brain amyloid PET results to allow cross-tracer and cross-methodology comparisons. The Centiloid anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scans. Florbetapir SUVr was converted to the Centiloid scale using the following conversion: Florbetapir Centiloids = 183 x SUVr-177. LS Mean was determined by using ANCOVA methodology. APD: All randomized participants who received at least one dose of study drug & have baseline and at least one post-baseline for amyloid burden.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    7
    10
    7
    Units: Units on a Scale
        least squares mean (standard error)
    -2.43 ± 10.47
    -0.21 ± 7.79
    -17.63 ± 9.69
    Statistical analysis title
    		 Florbetapir Amyloid Scan
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.873
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    2.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.569
         upper limit
    		 31.017
    Variability estimate
    Standard error of the mean
    Dispersion value
    13.76
    Statistical analysis title
    		 Florbetapir Amyloid Scan
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    14
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.337
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -15.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -47.488
         upper limit
    		 17.096
    Variability estimate
    Standard error of the mean
    Dispersion value
    15.43

    Secondary: Change from Baseline in Regional Cerebral Blood Flow (rCBF) using Florbetapir Perfusion Scan

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    End point title
    		 Change from Baseline in Regional Cerebral Blood Flow (rCBF) using Florbetapir Perfusion Scan
    End point description
    Florbetapir perfusion evaluated the regional cerebral blood flow (rCBF) as a biomarker of brain function and was performed at the same time as the amyloid florbetapir PET. Cerebral perfusion, especially in temporal and parietal areas, is reduced in AD and this pattern of hypoperfusion closely mirrors the hypometabolism pattern observed using FDG PET. Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA with LOCF (last observation carried forward) and with factors for treatment, baseline biomarker and age at baseline. APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for rCBF.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    82
    65
    66
    Units: Standard Uptake Value ratio (SUVr)
        least squares mean (standard error)
    -0.03 ± 0.01
    -0.03 ± 0.01
    -0.03 ± 0.01
    Statistical analysis title
    		 rCBF
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.927
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.015
         upper limit
    		 0.017
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.01
    Statistical analysis title
    		 rCBF
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    148
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.93
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.015
         upper limit
    		 0.017
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.01

    Secondary: Change from Baseline in Whole Brain Volume

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    End point title
    		 Change from Baseline in Whole Brain Volume
    End point description
    Magnetic resonance imaging (MRI) was used to evaluate the effect of lanabecestat on brain atrophy/whole brain volumes. Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline volumetric magnetic resonance imaging (vMRI), intracranial volume and age at baseline. APD: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for Whole Brain Volume.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    		 Placebo Lanabecestat 20 mg Lanabecestat 50 mg
    Number of subjects analysed
    215
    215
    214
    Units: cm^3 (cubic centimeter)
        least squares mean (standard error)
    -15.76 ± 0.75
    -17.38 ± 0.75
    -18.84 ± 0.76
    Statistical analysis title
    		 Whole Brain Volume
    Comparison groups
    Placebo v Lanabecestat 20 mg
    Number of subjects included in analysis
    430
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.127
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -1.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.708
         upper limit
    		 0.464
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.06
    Statistical analysis title
    		 Whole Brain Volume
    Comparison groups
    Placebo v Lanabecestat 50 mg
    Number of subjects included in analysis
    429
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean Difference (Final Values)
    Point estimate
    -3.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.172
         upper limit
    		 -0.991
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.06

    Secondary: Population Pharmacokinetics (PK): Apparent Oral Clearance of Lanabecestat

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    End point title
    		 Population Pharmacokinetics (PK): Apparent Oral Clearance of Lanabecestat
    End point description
    The apparent oral clearance of lanabecestat was estimated using a population approach. No covariate effects were assessed as part of this analysis. APD: All randomized participants who received at least 1 dose of study drug with evaluable PK data.
    End point type
    Secondary
    End point timeframe
    Predose, Week 4, 7, 19, 39, 45 and Week 71 post dose
    End point values
    		 Lanabecestat
    Number of subjects analysed
    1077
    Units: Liter per hour (L/h)
        geometric mean (geometric coefficient of variation)
    17.4 ± 38.8
    No statistical analyses for this end point

    Secondary: Population PK: Central Volume of Distribution of Lanabecestat

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    End point title
    		 Population PK: Central Volume of Distribution of Lanabecestat
    End point description
    The central volume of distribution for lanabecestat was estimated using a population approach. No covariate effects were assessed as part of this analysis. APD: All randomized participants who received at least 1 dose of study drug with evaluable PK data.
    End point type
    Secondary
    End point timeframe
    Predose, Week 4, 7, 19, 39, 45 and week 71 post dose
    End point values
    		 Lanabecestat
    Number of subjects analysed
    1077
    Units: Liters (L)
        geometric mean (geometric coefficient of variation)
    77.8 ± 198
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up To 156 Weeks
    Adverse event reporting additional description
    All randomized participants who received at least one dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Lanabecestat 20 mg-Period 1
    Reporting group description
    		 Participants received lanabecestat 20 mg film-coated oral tablets once daily.

    Reporting group title
    Lanabecestat 50 mg-Period 1
    Reporting group description
    		 Participants received lanabecestat 50 mg film-coated oral tablets once daily.

    Reporting group title
    Placebo-Period 1
    Reporting group description
    		 Participants received placebo film-coated oral tablets once daily.

    Reporting group title
    Lanabecestat 20 mg-Period 2
    Reporting group description
    		 Participants from placebo group were randomized to receive lanabecestat 20 mg film-coated oral tablets once daily.

    Reporting group title
    Lanabecestat 50 mg-Period 2
    Reporting group description
    		 Participants from placebo group were randomized to receive lanabecestat 50 mg film-coated oral tablets once daily.

    Serious adverse events
    		 Lanabecestat 20 mg-Period 1 Lanabecestat 50 mg-Period 1 Placebo-Period 1 Lanabecestat 20 mg-Period 2 Lanabecestat 50 mg-Period 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    50 / 588 (8.50%)
    46 / 568 (8.10%)
    50 / 558 (8.96%)
    0 / 14 (0.00%)
    1 / 12 (8.33%)
         number of deaths (all causes)
    2
    3
    5
    0
    0
         number of deaths resulting from adverse events
    1
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    adenocarcinoma of colon
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    adenocarcinoma pancreas
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    bladder transitional cell carcinoma
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    brain neoplasm
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    breast cancer
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colon cancer
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colorectal cancer
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    invasive ductal breast carcinoma
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    lung adenocarcinoma
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ovarian cancer recurrent
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed [1]
    0 / 333 (0.00%)
    1 / 339 (0.29%)
    0 / 347 (0.00%)
    0 / 9 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ovarian cancer stage ii
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed [2]
    0 / 333 (0.00%)
    0 / 339 (0.00%)
    1 / 347 (0.29%)
    0 / 9 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pancreatic carcinoma
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    papillary thyroid cancer
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    prostate cancer
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed [3]
    1 / 255 (0.39%)
    0 / 229 (0.00%)
    1 / 211 (0.47%)
    0 / 5 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    renal oncocytoma
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    squamous cell carcinoma of the tongue
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    deep vein thrombosis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypertension
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    peripheral ischaemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    thrombosis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    chest pain
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    death
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    feeling abnormal
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    non-cardiac chest pain
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    sudden cardiac death
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    anaphylactic reaction
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hiccups
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypoxia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    lung disorder
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    pleural effusion
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumonia aspiration
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumothorax
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    respiratory arrest
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Psychiatric disorders
    abnormal behaviour
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    acute psychosis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    adjustment disorder
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    aggression
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    confusional state
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    delirium
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    2 / 568 (0.35%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    delusion
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    mental status changes
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    2 / 558 (0.36%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    paranoia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    psychotic disorder
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    prostatic specific antigen increased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed [4]
    1 / 255 (0.39%)
    0 / 229 (0.00%)
    0 / 211 (0.00%)
    0 / 5 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    animal bite
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ankle fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    brain contusion
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    clavicle fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    craniocerebral injury
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    fall
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    3 / 588 (0.51%)
    5 / 568 (0.88%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    femoral neck fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    femur fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    1 / 568 (0.18%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    fibula fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    forearm fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    heat exhaustion
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hip fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    humerus fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    2 / 558 (0.36%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    lumbar vertebral fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pelvic fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    post procedural complication
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pubis fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    2 / 568 (0.35%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    rib fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    2 / 568 (0.35%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    road traffic accident
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    2 / 558 (0.36%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    spinal compression fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    spinal fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    subdural haematoma
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    tibia fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    upper limb fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    wrist fracture
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    gastrointestinal arteriovenous malformation
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    acute coronary syndrome
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    1 / 568 (0.18%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    acute myocardial infarction
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    atrial fibrillation
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    2 / 568 (0.35%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    atrial flutter
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    atrioventricular block complete
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac arrest
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    cardiac failure congestive
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardio-respiratory arrest
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    chronotropic incompetence
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coronary artery disease
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myocardial infarction
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    sinus node dysfunction
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    2 / 588 (0.34%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    stress cardiomyopathy
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    trifascicular block
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ventricular fibrillation
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    brain injury
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebellar haematoma
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebral infarction
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cerebrovascular accident
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    2 / 568 (0.35%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cognitive disorder
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    coma
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    dementia alzheimer's type
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    device malfunction
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    dizziness
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    2 / 558 (0.36%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    encephalopathy
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    generalised tonic-clonic seizure
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    haemorrhage intracranial
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    headache
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    presyncope
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    seizure
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    syncope
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    3 / 588 (0.51%)
    3 / 568 (0.53%)
    3 / 558 (0.54%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 4
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    toxic encephalopathy
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    iron deficiency anaemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    vertigo positional
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    colitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colitis ischaemic
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    constipation
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    2 / 568 (0.35%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diverticulum
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    inguinal hernia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    intestinal obstruction
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    peptic ulcer perforation
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    rectal prolapse
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    cholecystitis acute
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cholelithiasis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    acute kidney injury
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    2 / 558 (0.36%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    stress urinary incontinence
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    cervical spinal stenosis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    muscle haemorrhage
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    muscle spasms
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myalgia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    osteoarthritis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    bacteraemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    bronchitis viral
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cellulitis orbital
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    epididymitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed [5]
    1 / 255 (0.39%)
    0 / 229 (0.00%)
    1 / 211 (0.47%)
    0 / 5 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    erysipelas
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    liver abscess
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    orchitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed [6]
    0 / 255 (0.00%)
    0 / 229 (0.00%)
    1 / 211 (0.47%)
    0 / 5 (0.00%)
    0 / 7 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    1 / 568 (0.18%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    sinusitis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    urosepsis
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    1 / 568 (0.18%)
    1 / 558 (0.18%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    dehydration
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    2 / 588 (0.34%)
    1 / 568 (0.18%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypoglycaemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hyponatraemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    2 / 568 (0.35%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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 subjects. The number of subjects 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 subjects. The number of subjects 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 subjects. The number of subjects 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 subjects. The number of subjects 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 subjects. The number of subjects 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 subjects. The number of subjects exposed has been adjusted accordingly.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Lanabecestat 20 mg-Period 1 Lanabecestat 50 mg-Period 1 Placebo-Period 1 Lanabecestat 20 mg-Period 2 Lanabecestat 50 mg-Period 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    69 / 588 (11.73%)
    76 / 568 (13.38%)
    48 / 558 (8.60%)
    5 / 14 (35.71%)
    1 / 12 (8.33%)
    Investigations
    blood glucose decreased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    1 / 14 (7.14%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    thyroxine decreased
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    0 / 588 (0.00%)
    2 / 568 (0.35%)
    0 / 558 (0.00%)
    1 / 14 (7.14%)
    0 / 12 (0.00%)
         occurrences all number
    0
    2
    0
    1
    0
    Injury, poisoning and procedural complications
    fall
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    32 / 588 (5.44%)
    34 / 568 (5.99%)
    21 / 558 (3.76%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    37
    49
    34
    0
    0
    General disorders and administration site conditions
    influenza like illness
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    4 / 568 (0.70%)
    1 / 558 (0.18%)
    1 / 14 (7.14%)
    0 / 12 (0.00%)
         occurrences all number
    1
    4
    1
    1
    0
    Eye disorders
    glaucoma
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    4 / 588 (0.68%)
    3 / 568 (0.53%)
    5 / 558 (0.90%)
    1 / 14 (7.14%)
    0 / 12 (0.00%)
         occurrences all number
    4
    3
    5
    1
    0
    Reproductive system and breast disorders
    benign prostatic hyperplasia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed [7]
    4 / 255 (1.57%)
    3 / 229 (1.31%)
    4 / 211 (1.90%)
    1 / 5 (20.00%)
    0 / 7 (0.00%)
         occurrences all number
    4
    3
    4
    1
    0
    Gastrointestinal disorders
    diarrhoea
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    29 / 588 (4.93%)
    29 / 568 (5.11%)
    17 / 558 (3.05%)
    0 / 14 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    35
    39
    19
    0
    0
    Psychiatric disorders
    confusional state
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    4 / 588 (0.68%)
    9 / 568 (1.58%)
    2 / 558 (0.36%)
    1 / 14 (7.14%)
    0 / 12 (0.00%)
         occurrences all number
    4
    9
    2
    1
    0
    psychotic disorder
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    0 / 568 (0.00%)
    0 / 558 (0.00%)
    0 / 14 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    0
    0
    1
    Metabolism and nutrition disorders
    hyperlipidaemia
    alternative dictionary used: MedDRA 21.1
         subjects affected / exposed
    1 / 588 (0.17%)
    1 / 568 (0.18%)
    1 / 558 (0.18%)
    1 / 14 (7.14%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    1
    1
    0
    Notes
    [7] - 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 subjects. The number of subjects exposed has been adjusted accordingly.

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

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    An independent assessment concluded the trial was not likely to meet the primary endpoint upon completion and therefore, trial stopped for futility.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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