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    Clinical Trial Results:
    Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Safety, Tolerability, and Efficacy of BIIB092 in Subjects with Mild Cognitive Impairment due to Alzheimer’s Disease or with Mild Alzheimer’s Disease

    Summary
    EudraCT number
    2017-002901-37
    Trial protocol
    DE   SE   ES   IT   PL   FR  
    Global end of trial date
    30 Aug 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    11 Sep 2022
    First version publication date
    11 Sep 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    251AD201
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03352557
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Biogen
    Sponsor organisation address
    250 Binney Street, Cambridge, United States, 02142
    Public contact
    Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
    Scientific contact
    Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Aug 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Aug 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of the placebo-controlled (PC) period was to evaluate the safety and tolerability of BIIB092 in subjects with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) or with mild AD.
    Protection of trial subjects
    Written informed consent was obtained from each subject or subject’s legally authorised representative (e.g., legal guardian), as applicable, prior to evaluations performed for eligibility. Subjects or the subject’s legally authorised representative were given adequate time to review the information in the informed consent/assent and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    03 May 2018
    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
    France: 54
    Country: Number of subjects enrolled
    Poland: 41
    Country: Number of subjects enrolled
    Sweden: 19
    Country: Number of subjects enrolled
    Australia: 19
    Country: Number of subjects enrolled
    Japan: 19
    Country: Number of subjects enrolled
    United States: 355
    Country: Number of subjects enrolled
    Germany: 62
    Country: Number of subjects enrolled
    Italy: 27
    Country: Number of subjects enrolled
    Spain: 58
    Worldwide total number of subjects
    654
    EEA total number of subjects
    261
    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)
    146
    From 65 to 84 years
    508
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Subjects were enrolled at 100 investigational sites in United States,Australia,Germany,Spain,France,Italy,Japan,Poland and Sweden from 03 May 2018 to 30 August 2021. WBS=Withdrawal by Subject;WBP/G=Withdrawal by Parent/Guardian;SV=Study Visit;PR=Perceived Risks;CIT=Change in Treatment;EP=Enable Participation;I/H/D=Illness/Hospitalisation/Death

    Pre-assignment
    Screening details
    A total of 654 subjects with Alzheimer's Disease (AD) were enrolled and randomised to receive placebo or BIIB092 125/375/600/2000 milligrams (mg) in PC period. Following PC period, 521 subjects entered and 516 were dosed in Long-term Extension (LTE) period, and no subjects completed the study due to early termination of the study.

    Period 1
    Period 1 title
    PC Period: Day 1 to Week 78
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    PC Period: Placebo
    Arm description
    Subjects received BIIB092-matching placebo, intravenous (IV) infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
    Arm type
    Placebo

    Investigational medicinal product name
    BIIB092-matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    BIIB092-matching placebo administered via IV infusion, on Day 1 and then every 4 weeks for 76 weeks.

    Arm title
    PC Period: BIIB092 125 mg/4 week
    Arm description
    Subjects received BIIB092, 125 milligrams (mg), IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB092
    Investigational medicinal product code
    Other name
    Formally known as BMS 986168
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    BIIB092 125 mg administered via IV infusion, on Day 1 and then every 4 weeks for 76 weeks.

    Arm title
    PC Period: BIIB092 375 mg/12 week
    Arm description
    Subjects received BIIB092, 375 mg, IV infusion, on Day 1 and then once every 12 weeks for 76 weeks during the PC period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB092
    Investigational medicinal product code
    Other name
    Formally known as BMS 986168
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    BIIB092 375 mg administered via IV infusion, on Day 1 and then every 12 weeks for 76 weeks.

    Arm title
    PC Period: BIIB092 600 mg/4 week
    Arm description
    Subjects received BIIB092, 600 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB092
    Investigational medicinal product code
    Other name
    Formally known as BMS 986168
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    BIIB092 600 mg administered via IV infusion, on Day 1 and then every 4 weeks for 76 weeks.

    Arm title
    PC Period: BIIB092 2000 mg/4 week
    Arm description
    Subjects received BIIB092, 2000 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB092
    Investigational medicinal product code
    Other name
    Formally known as BMS 986168
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    BIIB092 2000 mg administered via IV infusion, on Day 1 and then every 4 weeks for 76 weeks.

    Number of subjects in period 1
    PC Period: Placebo PC Period: BIIB092 125 mg/4 week PC Period: BIIB092 375 mg/12 week PC Period: BIIB092 600 mg/4 week PC Period: BIIB092 2000 mg/4 week
    Started
    214
    58
    58
    106
    218
    Safety Analysis Set
    214
    58
    58
    106
    214
    Full Analysis Set (FAS)
    214
    58
    58
    106
    214
    Antidrug antibody (ADA) Evaluable Set
    211
    57
    57
    105
    212
    Completed
    172
    48
    50
    91
    175
    Not completed
    42
    10
    8
    15
    43
         WBS-Relocation (Moving or has Moved)
    1
    1
    -
    1
    1
         WBP/G-Other
    -
    2
    -
    -
    3
         WBP/G-SV Burden/Scheduling Conflicts
    -
    -
    -
    1
    3
         WBP/G-Desire for CIT (Unrelated to Safety)
    1
    -
    -
    -
    1
         Physician Decision-Unrelated to Safety
    2
    -
    -
    -
    1
         Adverse Event
    10
    1
    1
    -
    5
         Protocol Deviation
    1
    -
    -
    1
    2
         WBS-SV Burden/Scheduling Conflicts
    7
    1
    1
    -
    5
         WBS-Desire for CIT (Unrelated to Safety)
    -
    -
    1
    -
    1
         WBP/G-Unable to Continue to EP due to I/H/D
    -
    -
    -
    -
    1
         Site Terminated by Sponsor
    2
    1
    1
    1
    2
         WBS-Other
    6
    2
    2
    5
    7
         WBS-Concern About Study Procedures/PR
    1
    -
    -
    1
    2
         Noncompliance with Study Drug
    1
    -
    -
    -
    -
         Death
    1
    1
    -
    -
    1
         Progressive Disease
    -
    -
    -
    -
    1
         Not Specified
    5
    1
    -
    3
    -
         Randomised by Mistake
    2
    -
    -
    1
    -
         WBP/G-Concern About Study Procedures/PR
    1
    -
    1
    1
    1
         Not Dosed
    -
    -
    -
    -
    4
         Lost to follow-up
    1
    -
    1
    -
    2
    Period 2
    Period 2 title
    LTE Period: Week 80 to Week 173
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    LTE Period: BIIB092 125 mg/4 week
    Arm description
    Subjects who received BIIB092, 125 mg, IV infusion during the PC period, continued to receive BIIB092, 125 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB092
    Investigational medicinal product code
    Other name
    Formally known as BMS 986168
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    BIIB092 125 mg administered via IV infusion, once every 4 weeks from Week 80 to Week 155.

    Arm title
    LTE Period: BIIB092 375 mg/12 week
    Arm description
    Subjects who received BIIB092, 375 mg, IV infusion during the PC period, continued to receive BIIB092, 375 mg, IV infusion once every 12 weeks from Week 80 to Week 155 during the LTE period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB092
    Investigational medicinal product code
    Other name
    Formally known as BMS 986168
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    BIIB092 375 mg administered via IV infusion, once every 12 weeks from Week 80 to Week 155.

    Arm title
    LTE Period: BIIB092 600 mg/4 week
    Arm description
    Subjects who received BIIB092, 600 mg, IV infusion during the PC period, continued to receive BIIB092, 600 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB092
    Investigational medicinal product code
    Other name
    Formally known as BMS 986168
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    BIIB092 600 mg administered via IV infusion, once every 4 weeks from Week 80 to Week 155.

    Arm title
    LTE Period: BIIB092 2000 mg/4 week – Early Start
    Arm description
    Subjects who received BIIB092, 2000 mg, IV infusion during the PC period, continued to receive BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB092
    Investigational medicinal product code
    Other name
    Formally known as BMS 986168
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    BIIB092 2000 mg administered via IV infusion, once every 4 weeks from Week 80 to Week 155.

    Arm title
    LTE Period: BIIB092 2000 mg/4 week – Late Start
    Arm description
    Subjects who received BIIB092-matching placebo, IV infusion during the PC period, received BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.
    Arm type
    Experimental

    Investigational medicinal product name
    BIIB092
    Investigational medicinal product code
    Other name
    Formally known as BMS 986168
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    BIIB092 2000 mg administered via IV infusion, once every 4 weeks from Week 80 to Week 155.

    Number of subjects in period 2 [1]
    LTE Period: BIIB092 125 mg/4 week LTE Period: BIIB092 375 mg/12 week LTE Period: BIIB092 600 mg/4 week LTE Period: BIIB092 2000 mg/4 week – Early Start LTE Period: BIIB092 2000 mg/4 week – Late Start
    Started
    46
    49
    90
    169
    167
    Safety Analysis Set
    45
    49
    89
    168
    165
    Completed
    0
    0
    0
    0
    0
    Not completed
    46
    49
    90
    169
    167
         WBS-Relocation (Moving or has Moved)
    1
    -
    1
    1
    -
         WBP/G-Other
    1
    -
    -
    2
    -
         WBP/G-SV Burden/Scheduling Conflicts
    -
    -
    -
    2
    1
         Adverse Event
    3
    -
    -
    -
    -
         Physician Decision
    -
    -
    -
    -
    3
         WBS-SV Burden/Scheduling Conflicts
    1
    -
    5
    3
    3
         WBP/G-Unable to Continue to EP due to I/H/D
    -
    -
    2
    1
    -
         WBS-Other
    1
    -
    1
    1
    4
         Site Terminated by Sponsor
    -
    -
    -
    2
    -
         Study Terminated by Sponsor
    38
    49
    75
    151
    154
         Death
    1
    -
    1
    1
    1
         Progressive Disease
    -
    -
    1
    2
    -
         Not Specified
    -
    -
    1
    -
    -
         WBP/G-Concern About Study Procedures/PR
    -
    -
    1
    -
    -
         WBP/G-Relocation (Moving or has Moved)
    -
    -
    2
    -
    -
         Lost to follow-up
    -
    -
    -
    3
    1
    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: 536 subjects completed the PC period, out of which only 521 subjects entered in LTE period. 15 subjects from PC period did not enter LTE period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    PC Period: Placebo
    Reporting group description
    Subjects received BIIB092-matching placebo, intravenous (IV) infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 125 mg/4 week
    Reporting group description
    Subjects received BIIB092, 125 milligrams (mg), IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 375 mg/12 week
    Reporting group description
    Subjects received BIIB092, 375 mg, IV infusion, on Day 1 and then once every 12 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 600 mg/4 week
    Reporting group description
    Subjects received BIIB092, 600 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 2000 mg/4 week
    Reporting group description
    Subjects received BIIB092, 2000 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Reporting group values
    PC Period: Placebo PC Period: BIIB092 125 mg/4 week PC Period: BIIB092 375 mg/12 week PC Period: BIIB092 600 mg/4 week PC Period: BIIB092 2000 mg/4 week Total
    Number of subjects
    214 58 58 106 218 654
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    69.8 ( 6.63 ) 70.4 ( 6.80 ) 70.3 ( 6.79 ) 69.7 ( 6.66 ) 69.4 ( 7.11 ) -
    Gender Categorical
    Units: subjects
        Female
    106 28 26 55 114 329
        Male
    108 30 32 51 104 325
    Race
    Units: Subjects
        American Indian or Alaska Native
    1 0 0 0 0 1
        Asian
    5 3 2 6 7 23
        Native Hawaiian or Other Pacific Islander
    0 0 0 0 0 0
        Black or African American
    4 0 1 1 1 7
        White
    201 53 53 98 206 611
        More than one race
    0 0 0 0 0 0
        Unknown or Not Reported
    3 2 2 1 4 12
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    3 2 2 1 9 17
        Not Hispanic or Latino
    208 53 55 103 208 627
        Unknown or Not Reported
    3 3 1 2 1 10

    End points

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    End points reporting groups
    Reporting group title
    PC Period: Placebo
    Reporting group description
    Subjects received BIIB092-matching placebo, intravenous (IV) infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 125 mg/4 week
    Reporting group description
    Subjects received BIIB092, 125 milligrams (mg), IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 375 mg/12 week
    Reporting group description
    Subjects received BIIB092, 375 mg, IV infusion, on Day 1 and then once every 12 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 600 mg/4 week
    Reporting group description
    Subjects received BIIB092, 600 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 2000 mg/4 week
    Reporting group description
    Subjects received BIIB092, 2000 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.
    Reporting group title
    LTE Period: BIIB092 125 mg/4 week
    Reporting group description
    Subjects who received BIIB092, 125 mg, IV infusion during the PC period, continued to receive BIIB092, 125 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.

    Reporting group title
    LTE Period: BIIB092 375 mg/12 week
    Reporting group description
    Subjects who received BIIB092, 375 mg, IV infusion during the PC period, continued to receive BIIB092, 375 mg, IV infusion once every 12 weeks from Week 80 to Week 155 during the LTE period.

    Reporting group title
    LTE Period: BIIB092 600 mg/4 week
    Reporting group description
    Subjects who received BIIB092, 600 mg, IV infusion during the PC period, continued to receive BIIB092, 600 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.

    Reporting group title
    LTE Period: BIIB092 2000 mg/4 week – Early Start
    Reporting group description
    Subjects who received BIIB092, 2000 mg, IV infusion during the PC period, continued to receive BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.

    Reporting group title
    LTE Period: BIIB092 2000 mg/4 week – Late Start
    Reporting group description
    Subjects who received BIIB092-matching placebo, IV infusion during the PC period, received BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.

    Subject analysis set title
    PC Period: Placebo
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received BIIB092-matching placebo, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Subject analysis set title
    PC Period: BIIB092 Low Dose
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received BIIB092, 125 mg, IV infusion, on Day 1 and then once every 4 weeks or BIIB092, 375 mg, IV infusion, on Day 1 and then once every 12 weeks for 76 weeks during the PC period.

    Subject analysis set title
    PC Period: BIIB092 600 mg/4 week
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received BIIB092, 600 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Subject analysis set title
    PC Period: BIIB092 2000 mg/4 week
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received BIIB092, 2000 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Primary: PC Period: Percentage of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    PC Period: Percentage of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) [1]
    End point description
    An AE is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the subject at immediate risk of death; requires inpatient hospitalisation or prolongation of existing hospitalisation; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event. The safety analysis set included all randomised subjects who received at least one dose of study treatment (BIIB092 or placebo).
    End point type
    Primary
    End point timeframe
    From Day 1 to Week 90
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    PC Period: Placebo PC Period: BIIB092 125 mg/4 week PC Period: BIIB092 375 mg/12 week PC Period: BIIB092 600 mg/4 week PC Period: BIIB092 2000 mg/4 week
    Number of subjects analysed
    214
    58
    58
    106
    214
    Units: percentage of subjects
    number (not applicable)
        AEs
    84.6
    86.2
    82.8
    88.7
    88.3
        SAEs
    12.1
    10.3
    10.3
    12.3
    11.7
    No statistical analyses for this end point

    Primary: LTE Period: Percentage of Subjects With AEs and SAEs

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    End point title
    LTE Period: Percentage of Subjects With AEs and SAEs [2]
    End point description
    An AE is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose, results in death; in the view of the investigator places the subject at immediate risk of death; requires inpatient hospitalisation or prolongation of existing hospitalisation; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event. The safety analysis set included all randomised subjects who received at least one dose of study treatment (BIIB092 or placebo).
    End point type
    Primary
    End point timeframe
    From Week 80 to Week 173
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was planned for this endpoint.
    End point values
    LTE Period: BIIB092 125 mg/4 week LTE Period: BIIB092 375 mg/12 week LTE Period: BIIB092 600 mg/4 week LTE Period: BIIB092 2000 mg/4 week – Early Start LTE Period: BIIB092 2000 mg/4 week – Late Start
    Number of subjects analysed
    45
    49
    89
    168
    165
    Units: percentage of subjects
    number (not applicable)
        AEs
    68.9
    55.1
    58.4
    61.3
    60.0
        SAEs
    11.1
    2.0
    10.1
    6.0
    7.9
    No statistical analyses for this end point

    Secondary: PC Period: Change From Baseline Over Time at Week 78 on the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score

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    End point title
    PC Period: Change From Baseline Over Time at Week 78 on the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score
    End point description
    The CDR-SB is a validated clinical assessment of global function in subjects with AD. The CDR is comprised of 6 domains: Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care. CDR-SB is the sum of the scores for these 6 domains. Impairment is scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or "box scores", can be added together to give the CDR-SB score which ranges from 0 (none) to 18 (severe impairment). FAS included all randomised subjects who received study treatment (BIIB092 or placebo). The 'n' signifies number of subjects analysed at the specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 78
    End point values
    PC Period: Placebo PC Period: BIIB092 Low Dose PC Period: BIIB092 600 mg/4 week PC Period: BIIB092 2000 mg/4 week
    Number of subjects analysed
    214
    116
    106
    214
    Units: score on a scale
    arithmetic mean (standard deviation)
        Baseline (n=214,116,106,214)
    3.07 ( 1.467 )
    2.92 ( 1.620 )
    3.24 ( 1.557 )
    3.04 ( 1.378 )
        Change at Week 78 (n=170,98,91,174)
    1.71 ( 2.376 )
    2.10 ( 2.375 )
    2.23 ( 2.987 )
    1.76 ( 2.038 )
    No statistical analyses for this end point

    Secondary: PC Period: Percentage of Subjects With Anti-BIIB092 Antibodies in Serum

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    End point title
    PC Period: Percentage of Subjects With Anti-BIIB092 Antibodies in Serum
    End point description
    The ADA evaluable set is defined as subjects in the FAS who have an evaluable postbaseline ADA sample.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 76
    End point values
    PC Period: Placebo PC Period: BIIB092 125 mg/4 week PC Period: BIIB092 375 mg/12 week PC Period: BIIB092 600 mg/4 week PC Period: BIIB092 2000 mg/4 week
    Number of subjects analysed
    211
    57
    57
    105
    212
    Units: percentage of subjects
        number (not applicable)
    1.9
    0
    0
    1.0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose through 14 weeks after last dose of study drug (Up to approximately 173 weeks)
    Adverse event reporting additional description
    The safety analysis set included all randomised subjects who received at least one dose of study treatment (BIIB092 or placebo). The total number of deaths (all causes) data and adverse events are reported for 'safety analysis set'.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    PC Period: Placebo
    Reporting group description
    Subjects received BIIB092-matching placebo, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 125 mg/4 week
    Reporting group description
    Subjects received BIIB092, 125 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 375 mg/12 week
    Reporting group description
    Subjects received BIIB092, 375 mg, IV infusion, on Day 1 and then once every 12 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 600 mg/4 week
    Reporting group description
    Subjects received BIIB092, 600 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Reporting group title
    PC Period: BIIB092 2000 mg/4 week
    Reporting group description
    Subjects received BIIB092, 2000 mg, IV infusion, on Day 1 and then once every 4 weeks for 76 weeks during the PC period.

    Reporting group title
    LTE Period: BIIB092 600 mg/4 week
    Reporting group description
    Subjects who received BIIB092, 600 mg, IV infusion during the PC period, continued to receive BIIB092, 600 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.

    Reporting group title
    LTE Period: BIIB092 125 mg/4 week
    Reporting group description
    Subjects who received BIIB092, 125 mg, IV infusion during the PC period, continued to receive BIIB092, 125 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.

    Reporting group title
    LTE Period: BIIB092 375 mg/12 week
    Reporting group description
    Subjects who received BIIB092, 375 mg, IV infusion during the PC period, continued to receive BIIB092, 375 mg, IV infusion once every 12 weeks from Week 80 to Week 155 during the LTE period.

    Reporting group title
    LTE Period: BIIB092 2000 mg/4 week – Early Start
    Reporting group description
    Subjects who received BIIB092, 2000 mg, IV infusion during the PC period, continued to receive BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.

    Reporting group title
    LTE Period: BIIB092 2000 mg/4 week – Late Start
    Reporting group description
    Subjects who received BIIB092-matching placebo, IV infusion during the PC period, received BIIB092, 2000 mg, IV infusion once every 4 weeks from Week 80 to Week 155 during the LTE period.

    Serious adverse events
    PC Period: Placebo PC Period: BIIB092 125 mg/4 week PC Period: BIIB092 375 mg/12 week PC Period: BIIB092 600 mg/4 week PC Period: BIIB092 2000 mg/4 week LTE Period: BIIB092 600 mg/4 week LTE Period: BIIB092 125 mg/4 week LTE Period: BIIB092 375 mg/12 week LTE Period: BIIB092 2000 mg/4 week – Early Start LTE Period: BIIB092 2000 mg/4 week – Late Start
    Total subjects affected by serious adverse events
         subjects affected / exposed
    26 / 214 (12.15%)
    6 / 58 (10.34%)
    6 / 58 (10.34%)
    13 / 106 (12.26%)
    25 / 214 (11.68%)
    9 / 89 (10.11%)
    5 / 45 (11.11%)
    1 / 49 (2.04%)
    10 / 168 (5.95%)
    13 / 165 (7.88%)
         number of deaths (all causes)
    1
    1
    0
    0
    1
    1
    2
    0
    1
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer recurrent
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer stage II
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive breast carcinoma
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma stage III
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    1 / 58 (1.72%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Penile squamous cell carcinoma
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    1 / 58 (1.72%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    1 / 45 (2.22%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    1 / 106 (0.94%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    1 / 45 (2.22%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Female genital tract fistula
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    1 / 106 (0.94%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Organising pneumonia
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    1 / 45 (2.22%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    2 / 214 (0.93%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delusion
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    1 / 49 (2.04%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    1 / 58 (1.72%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    1 / 106 (0.94%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    1 / 45 (2.22%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post lumbar puncture syndrome
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    1 / 106 (0.94%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    1 / 58 (1.72%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    2 / 214 (0.93%)
    1 / 58 (1.72%)
    1 / 58 (1.72%)
    1 / 106 (0.94%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    1 / 49 (2.04%)
    3 / 168 (1.79%)
    3 / 165 (1.82%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    1 / 49 (2.04%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    2 / 106 (1.89%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    1 / 45 (2.22%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic encephalopathy
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    1 / 106 (0.94%)
    2 / 214 (0.93%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    1 / 89 (1.12%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    1 / 106 (0.94%)
    1 / 214 (0.47%)
    1 / 89 (1.12%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dementia Alzheimer's type
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    1 / 106 (0.94%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    1 / 45 (2.22%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Idiopathic orbital inflammation
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    1 / 89 (1.12%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterovesical fistula
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    1 / 106 (0.94%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    1 / 58 (1.72%)
    1 / 106 (0.94%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal stenosis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal ulcer haemorrhage
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    1 / 45 (2.22%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal prolapse
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis acute
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    1 / 89 (1.12%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    2 / 106 (1.89%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    1 / 89 (1.12%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    1 / 89 (1.12%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Escherichia sepsis
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic abscess
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    1 / 106 (0.94%)
    0 / 214 (0.00%)
    1 / 89 (1.12%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 214 (0.47%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    1 / 89 (1.12%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    1 / 58 (1.72%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    1 / 89 (1.12%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    1 / 89 (1.12%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal abscess
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    1 / 165 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    1 / 168 (0.60%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    PC Period: Placebo PC Period: BIIB092 125 mg/4 week PC Period: BIIB092 375 mg/12 week PC Period: BIIB092 600 mg/4 week PC Period: BIIB092 2000 mg/4 week LTE Period: BIIB092 600 mg/4 week LTE Period: BIIB092 125 mg/4 week LTE Period: BIIB092 375 mg/12 week LTE Period: BIIB092 2000 mg/4 week – Early Start LTE Period: BIIB092 2000 mg/4 week – Late Start
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    121 / 214 (56.54%)
    39 / 58 (67.24%)
    38 / 58 (65.52%)
    68 / 106 (64.15%)
    139 / 214 (64.95%)
    19 / 89 (21.35%)
    10 / 45 (22.22%)
    11 / 49 (22.45%)
    28 / 168 (16.67%)
    29 / 165 (17.58%)
    Investigations
    Weight decreased
         subjects affected / exposed
    4 / 214 (1.87%)
    2 / 58 (3.45%)
    3 / 58 (5.17%)
    3 / 106 (2.83%)
    5 / 214 (2.34%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    4
    2
    3
    3
    5
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    6 / 214 (2.80%)
    0 / 58 (0.00%)
    1 / 58 (1.72%)
    8 / 106 (7.55%)
    5 / 214 (2.34%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    8
    0
    2
    8
    8
    0
    0
    0
    0
    0
    Fall
         subjects affected / exposed
    23 / 214 (10.75%)
    6 / 58 (10.34%)
    11 / 58 (18.97%)
    19 / 106 (17.92%)
    30 / 214 (14.02%)
    6 / 89 (6.74%)
    5 / 45 (11.11%)
    7 / 49 (14.29%)
    14 / 168 (8.33%)
    15 / 165 (9.09%)
         occurrences all number
    26
    7
    13
    20
    35
    6
    8
    7
    17
    18
    Limb injury
         subjects affected / exposed
    0 / 214 (0.00%)
    1 / 58 (1.72%)
    3 / 58 (5.17%)
    1 / 106 (0.94%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    0
    1
    3
    1
    1
    0
    0
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    14 / 214 (6.54%)
    5 / 58 (8.62%)
    3 / 58 (5.17%)
    6 / 106 (5.66%)
    13 / 214 (6.07%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    18
    6
    3
    6
    18
    0
    0
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    13 / 214 (6.07%)
    5 / 58 (8.62%)
    2 / 58 (3.45%)
    9 / 106 (8.49%)
    11 / 214 (5.14%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    15
    8
    2
    11
    13
    0
    0
    0
    0
    0
    Headache
         subjects affected / exposed
    20 / 214 (9.35%)
    1 / 58 (1.72%)
    6 / 58 (10.34%)
    11 / 106 (10.38%)
    22 / 214 (10.28%)
    4 / 89 (4.49%)
    1 / 45 (2.22%)
    3 / 49 (6.12%)
    3 / 168 (1.79%)
    6 / 165 (3.64%)
         occurrences all number
    27
    1
    11
    19
    31
    4
    2
    3
    4
    8
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    7 / 214 (3.27%)
    1 / 58 (1.72%)
    4 / 58 (6.90%)
    8 / 106 (7.55%)
    12 / 214 (5.61%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    9
    1
    5
    9
    13
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    8 / 214 (3.74%)
    5 / 58 (8.62%)
    1 / 58 (1.72%)
    2 / 106 (1.89%)
    6 / 214 (2.80%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    8
    5
    1
    2
    6
    0
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    12 / 214 (5.61%)
    11 / 58 (18.97%)
    3 / 58 (5.17%)
    6 / 106 (5.66%)
    11 / 214 (5.14%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    15
    14
    4
    9
    11
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    13 / 214 (6.07%)
    4 / 58 (6.90%)
    2 / 58 (3.45%)
    6 / 106 (5.66%)
    11 / 214 (5.14%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    16
    4
    2
    9
    14
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 214 (2.34%)
    1 / 58 (1.72%)
    3 / 58 (5.17%)
    7 / 106 (6.60%)
    16 / 214 (7.48%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    5
    1
    3
    7
    20
    0
    0
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 214 (0.47%)
    1 / 58 (1.72%)
    3 / 58 (5.17%)
    1 / 106 (0.94%)
    2 / 214 (0.93%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    1
    1
    3
    1
    2
    0
    0
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    11 / 214 (5.14%)
    4 / 58 (6.90%)
    2 / 58 (3.45%)
    3 / 106 (2.83%)
    15 / 214 (7.01%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    12
    5
    2
    3
    17
    0
    0
    0
    0
    0
    Confusional state
         subjects affected / exposed
    5 / 214 (2.34%)
    4 / 58 (6.90%)
    0 / 58 (0.00%)
    4 / 106 (3.77%)
    2 / 214 (0.93%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    5
    5
    0
    6
    3
    0
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    13 / 214 (6.07%)
    4 / 58 (6.90%)
    2 / 58 (3.45%)
    4 / 106 (3.77%)
    11 / 214 (5.14%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    13
    4
    2
    4
    11
    0
    0
    0
    0
    0
    Disorientation
         subjects affected / exposed
    2 / 214 (0.93%)
    3 / 58 (5.17%)
    1 / 58 (1.72%)
    1 / 106 (0.94%)
    1 / 214 (0.47%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    3
    3
    1
    1
    1
    0
    0
    0
    0
    0
    Irritability
         subjects affected / exposed
    2 / 214 (0.93%)
    3 / 58 (5.17%)
    2 / 58 (3.45%)
    3 / 106 (2.83%)
    3 / 214 (1.40%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    2
    4
    3
    3
    3
    0
    0
    0
    0
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    0 / 214 (0.00%)
    3 / 58 (5.17%)
    1 / 58 (1.72%)
    0 / 106 (0.00%)
    3 / 214 (1.40%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    0
    4
    1
    0
    3
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    14 / 214 (6.54%)
    6 / 58 (10.34%)
    7 / 58 (12.07%)
    9 / 106 (8.49%)
    19 / 214 (8.88%)
    4 / 89 (4.49%)
    0 / 45 (0.00%)
    3 / 49 (6.12%)
    6 / 168 (3.57%)
    3 / 165 (1.82%)
         occurrences all number
    16
    7
    7
    11
    23
    4
    0
    4
    9
    3
    Back pain
         subjects affected / exposed
    16 / 214 (7.48%)
    5 / 58 (8.62%)
    3 / 58 (5.17%)
    9 / 106 (8.49%)
    13 / 214 (6.07%)
    2 / 89 (2.25%)
    3 / 45 (6.67%)
    0 / 49 (0.00%)
    5 / 168 (2.98%)
    5 / 165 (3.03%)
         occurrences all number
    18
    5
    4
    10
    16
    2
    3
    0
    5
    12
    Muscle spasms
         subjects affected / exposed
    3 / 214 (1.40%)
    3 / 58 (5.17%)
    0 / 58 (0.00%)
    3 / 106 (2.83%)
    7 / 214 (3.27%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    3
    3
    0
    3
    8
    0
    0
    0
    0
    0
    Neck pain
         subjects affected / exposed
    2 / 214 (0.93%)
    3 / 58 (5.17%)
    0 / 58 (0.00%)
    2 / 106 (1.89%)
    5 / 214 (2.34%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    2
    3
    0
    2
    5
    0
    0
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    22 / 214 (10.28%)
    4 / 58 (6.90%)
    6 / 58 (10.34%)
    9 / 106 (8.49%)
    24 / 214 (11.21%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    26
    5
    7
    12
    29
    0
    0
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    2 / 214 (0.93%)
    3 / 58 (5.17%)
    0 / 58 (0.00%)
    1 / 106 (0.94%)
    7 / 214 (3.27%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    3
    3
    0
    1
    8
    0
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    15 / 214 (7.01%)
    5 / 58 (8.62%)
    3 / 58 (5.17%)
    6 / 106 (5.66%)
    15 / 214 (7.01%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    19
    6
    3
    7
    18
    0
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    13 / 214 (6.07%)
    5 / 58 (8.62%)
    3 / 58 (5.17%)
    8 / 106 (7.55%)
    20 / 214 (9.35%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    17
    6
    5
    11
    26
    0
    0
    0
    0
    0
    COVID-19
         subjects affected / exposed
    0 / 214 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    0 / 214 (0.00%)
    9 / 89 (10.11%)
    2 / 45 (4.44%)
    1 / 49 (2.04%)
    2 / 168 (1.19%)
    3 / 165 (1.82%)
         occurrences all number
    0
    0
    0
    0
    0
    9
    2
    1
    3
    3
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 214 (0.93%)
    3 / 58 (5.17%)
    0 / 58 (0.00%)
    0 / 106 (0.00%)
    2 / 214 (0.93%)
    0 / 89 (0.00%)
    0 / 45 (0.00%)
    0 / 49 (0.00%)
    0 / 168 (0.00%)
    0 / 165 (0.00%)
         occurrences all number
    2
    3
    0
    0
    2
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Sep 2018
    Updated the list of allowed concomitant medications for subjects enrolled in this study, washout period of Alzheimer’s disease (AD) medications, added the requirement for stable doses of key concomitant medications prior to and during Screening and for the duration of the study.
    29 Mar 2019
    Added a dose-blinded long-term extension (LTE) period of approximately 3 years. The primary purpose of the LTE was to obtain long-term safety and tolerability information on BIIB092 and further explore its effects on immunogenicity, disease progression, and additional clinical and health outcomes.
    13 Jan 2020
    Updated the number of randomised subjects from 528 to 654.

    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.
    The study was terminated based on lack of efficacy following the placebo-controlled period readout.
    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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