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    Clinical Trial Results:
    A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Brodalumab in Subjects With Psoriatic Arthritis: AMVISION-2

    Summary
    EudraCT number
    2013-003553-16
    Trial protocol
    GR   DE   HU   LV  
    Global end of trial date
    01 Oct 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    16 Oct 2016
    First version publication date
    16 Oct 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20110144
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02024646
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Amgen, Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.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
    01 Oct 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Oct 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the efficacy of brodalumab compared to placebo, in patients with psoriatic arthritis, as measured by the proportion of subjects achieving an American College of Rheumatology 20% response (ACR20) response at week 16.
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with the International Conference on Harmonisation’s (ICH) guideline for Good Clinical Practice (GCP), applicable regulatory requirements, and the Sponsor’s applicable policies. The clinical study protocol (CSP) was reviewed and approved by an independent ethics committee (IEC) or institutional review board (IRB) at each clinical site prior to the enrollment of any study subjects. All subjects provided written informed consent before undergoing any study-related procedures, including screening procedures.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    24 Mar 2014
    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
    United States: 122
    Country: Number of subjects enrolled
    Russian Federation: 56
    Country: Number of subjects enrolled
    Poland: 177
    Country: Number of subjects enrolled
    Canada: 32
    Country: Number of subjects enrolled
    Germany: 27
    Country: Number of subjects enrolled
    Hungary: 20
    Country: Number of subjects enrolled
    Latvia: 15
    Country: Number of subjects enrolled
    Mexico: 13
    Country: Number of subjects enrolled
    France: 11
    Country: Number of subjects enrolled
    Greece: 11
    Worldwide total number of subjects
    484
    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)
    446
    From 65 to 84 years
    38
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Patients were recruited at 89 clinical centers in 10 countries worldwide. The first subject was randomized on 24 March 2014.

    Pre-assignment
    Screening details
    Eligible patients were randomized in a 1:1:1 ratio by interactive web response (IWR) system to receive either brodalumab (140 mg or 210 mg) or placebo. Randomization was stratified by baseline body weight (≤100 kg or >100 kg), prior use of a biologic, and geographic region.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Participants received placebo subcutaneous injection at baseline, week 1, week 2 and then every 2 weeks (Q2W) thereafter up to week 22. From week 14 participants with an inadequate response began treatment with 210 mg brodalumab Q2W. From Week 24 all participants received brodalumab 210 mg Q2W.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once every 2 weeks.

    Investigational medicinal product name
    Brodalumab
    Investigational medicinal product code
    AMG 827
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once every 2 weeks.

    Arm title
    Brodalumab 140 mg
    Arm description
    Participants received 140 mg brodalumab by subcutaneous injection at baseline, week 1, week 2 and then Q2W thereafter for up to 3 years.
    Arm type
    Experimental

    Investigational medicinal product name
    Brodalumab
    Investigational medicinal product code
    AMG 827
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once every 2 weeks.

    Arm title
    Brodalumab 210 mg
    Arm description
    Participants received 210 mg brodalumab by subcutaneous injection at baseline, week 1, week 2 and then Q2W thereafter for up to 3 years.
    Arm type
    Experimental

    Investigational medicinal product name
    Brodalumab
    Investigational medicinal product code
    AMG 827
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection once every 2 weeks.

    Number of subjects in period 1
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Started
    161
    160
    163
    Ongoing study at week 16
    146
    152
    149
    Ongoing study at week 24
    129
    134
    129
    Ongoing study at week 52
    41
    45
    40
    Completed
    0
    0
    0
    Not completed
    161
    160
    163
         Sponsor’s decision
    133
    143
    133
         Consent withdrawn by subject
    27
    15
    25
         Lost to follow-up
    1
    2
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received placebo subcutaneous injection at baseline, week 1, week 2 and then every 2 weeks (Q2W) thereafter up to week 22. From week 14 participants with an inadequate response began treatment with 210 mg brodalumab Q2W. From Week 24 all participants received brodalumab 210 mg Q2W.

    Reporting group title
    Brodalumab 140 mg
    Reporting group description
    Participants received 140 mg brodalumab by subcutaneous injection at baseline, week 1, week 2 and then Q2W thereafter for up to 3 years.

    Reporting group title
    Brodalumab 210 mg
    Reporting group description
    Participants received 210 mg brodalumab by subcutaneous injection at baseline, week 1, week 2 and then Q2W thereafter for up to 3 years.

    Reporting group values
    Placebo Brodalumab 140 mg Brodalumab 210 mg Total
    Number of subjects
    161 160 163 484
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    150 146 150 446
        From 65-84 years
    11 14 13 38
        85 years and over
    0 0 0 0
    Age Continuous
    Units: years
        median (full range (min-max))
    49 (18 to 76) 48 (22 to 80) 45 (19 to 79) -
    Gender Categorical
    Units: Subjects
        Female
    85 80 84 249
        Male
    76 80 79 235
    Race
    Units: Subjects
        White
    154 150 159 463
        Black or African American
    0 1 0 1
        Asian
    1 0 0 1
        American Indian or Alaska Native
    3 5 2 10
        Other
    3 4 2 9
    Tender joint count
    Units: joints
        arithmetic mean (standard deviation)
    20.9 ± 14.33 20.5 ± 15.66 17.2 ± 12.5 -
    Swollen joint count
    Units: joints
        arithmetic mean (standard deviation)
    11 ± 8.55 11.4 ± 9.19 11.1 ± 8.49 -
    Disease Activity Score 28-C-Reactive Protein (DAS28-CRP)
    The DAS28-CRP is a composite score to measure disease activity in patients with arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count;• C-reactive protein (CRP) level • Patient's global assessment of disease activity assessed on a score from 0 to 100. The DAS28-CRP score ranges from approximately zero to ten. Higher DAS28-CRP scores indicate higher disease activity.Data available for 157, 160, 160 subjects in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    4.6 ± 1.09 4.8 ± 1.08 4.6 ± 1.08 -
    Health Assessment Questionnaire – Disability Index (HAQ-DI)
    The HAQ-DI asks subjects about the degree of difficulty they have in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores). Responses in each functional area are scored from 0 indicating no difficulty to 3 indicating inability to perform a task in that area. The overall score is the average of the 8 category scores and ranges from 0 (no disability) to 3 (very severe, high dependency disability).
    Units: units on a scale
        arithmetic mean (standard deviation)
    1.1 ± 0.61 1.1 ± 0.7 1.1 ± 0.61 -
    Enthesitis score
    The enthesitis count is defined as the total number of 6 sites that have enthesitis. The sites assessed were: Lateral epicondyle (left/right), Medial femoral condyle (left/right), Achilles tendon insertion (left/right).
    Units: entheses
        arithmetic mean (standard deviation)
    1.7 ± 1.78 1.7 ± 1.95 1.6 ± 1.81 -
    Dactylitis score
    The dactylitis count is defined as the sum of 20 fingers/toes that exhibit dactylitis (absent 0, present 1).
    Units: digits
        arithmetic mean (standard deviation)
    2.4 ± 3.99 1.7 ± 3.37 1.9 ± 3.45 -
    Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
    BASDAI is a self-administered questionnaire composed of six items using an 11-point numerical rating scale from “0 = none” to “10 = very severe” for the first five items, and “0 = 0 hours” to “10 = 2 or more hours” for the sixth item that asks about the duration of morning stiffness. The BASDAI assesses the severity of fatigue, spinal and peripheral joint pain, localized tenderness, and morning stiffness. The final BASDAI score averages the individual assessments for a final score range of 0-10. Data available for 159, 160, and 162 subjects in each group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    5.2 ± 2.09 5 ± 2.3 5 ± 2.16 -
    Psoriasis Area and Severity Index (PASI) Score
    The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Data available for 160, 160, 163 subjects in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    8.9 ± 9.86 9 ± 11.23 7.9 ± 9.36 -
    Nail Psoriasis Severity Index (NAPSI)
    The NAPSI scale is an objective, numeric, and reproducible grading system for nail psoriasis that incorporates the many different features of nail psoriasis. Each quarter of the nail was scored for the presence (1) or absence (0) of 8 clinical features for a score of 0-4 for each feature. The total score for each nail ranges from 0 (absent) to 32 (worst). Data are reported for the worst nail for subjects with baseline nail involvement (58, 64 and 70 participants in each treatment group respectively).
    Units: units on a scale
        arithmetic mean (standard deviation)
    10.2 ± 4.19 9.8 ± 5.29 9.4 ± 3.51 -
    Dermatology Life Quality Index (DLQI)
    The DLQI is a skin disease-specific instrument to evaluate health-related quality of life. Participants evaluate the degree that psoriasis has affected their quality of life in the last week, including symptoms and feelings, daily and leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the total score ranges from 0 (best possible score) to 30 (worst possible score). Data are available for 159, 160, 162 participants in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    9.7 ± 7.33 9.2 ± 7.23 9.1 ± 7.7 -
    Psoriasis Severity Index (PSI) average Weekly Total Score
    The Psoriasis Symptom Inventory consists of eight psoriasis-specific items. Participants rated the severity of their symptoms in the last 24 hours on a scale from ‘not at all’ (0) to ‘very severe’ (4) in an electronic diary once a day. Total scores range from 0 to 32 with higher scores indicating worse symptoms. The daily assessment of the Psoriasis Symptom Inventory was analyzed as a weekly average. Data are available for 152, 144, and 148 participants in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    15 ± 7.6 13.9 ± 7.68 13.8 ± 8.58 -
    Clinical Disease Activity Index (CDAI)
    The Clinical Disease Activity Index (CDAI) is a composite index that is calculated from: • 28 tender joint count, • 28 swollen joint count, • Patient's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician's Global Assessment of Disease Activity - measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. Data available for 157, 156, 162 subjects in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    27.3 ± 12.59 29.4 ± 13.13 26.6 ± 12.76 -
    Physician Global Assessment of Disease Activity
    Assessed on a 100 mm visual analog scale (VAS) from 0 (Very Well ) on the left to 100 (Very Poorly) on the right end of the line. Data available for 157, 156, 162 subjects in each treatment group respectively
    Units: mm
        arithmetic mean (standard deviation)
    56.6 ± 20.12 58.5 ± 18.79 57.3 ± 20.18 -
    Patient Global Assessment of Disease
    Assessed on a 100 mm VAS from 0 (Very Well) on the left end of the line to 10 (Very Poorly) on the right. Data available for 159, 160, 162 subjects in each treatment group respectively.
    Units: mm
        arithmetic mean (standard deviation)
    56.7 ± 21.84 57.5 ± 22.01 53.6 ± 23.65 -
    Patient Global Assessment of Joint Pain
    Assessed on a 100 mm VAS from 0 (No Pain At All) to 100 (Worst Pain Imaginable). Data available for 159, 160, 162 subjects in each treatment group respectively.
    Units: mm
        arithmetic mean (standard deviation)
    50.4 ± 23.29 49.3 ± 24.61 48 ± 23.84 -
    Medical Outcomes Short Form-36 (SF-36) Physical Component Score
    The SF-36 assesses the general quality of life by evaluating the domains of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The questionnaire consists of 36 questions that are completed by the participant. The individual domain scores are aggregated to derive a physical-component summary score and a mental-component summary score which range from 0 to 100, with higher scores indicating a better level of functioning. Data are available for 159, 160, 162 participants in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    37.2 ± 9.45 36 ± 9.94 37.1 ± 9.46 -
    SF-36 Mental Component Score
    The SF-36 assesses the general quality of life by evaluating the domains of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The questionnaire consists of 36 questions that are completed by the participant. The individual domain scores are aggregated to derive a physical-component summary score and a mental-component summary score which range from 0 to 100, with higher scores indicating a better level of functioning. Data are available for 159, 160, 162 participants in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    50.5 ± 11.01 52.6 ± 9.6 51.1 ± 9.45 -
    C-Reactive Protein (CRP)
    Data available for 159, 160, 161 subjects in each treatment group respectively.
    Units: mg/L
        arithmetic mean (standard deviation)
    8.2 ± 13.71 9.9 ± 18.2 8.7 ± 13.01 -
    Erythrocyte Sedimentation Rate (ESR)
    Data available for 153, 157, 158 subjects in each treatment group respectively.
    Units: mm/hr
        arithmetic mean (standard deviation)
    23.3 ± 21.04 29.1 ± 23.49 27 ± 19.7 -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received placebo subcutaneous injection at baseline, week 1, week 2 and then every 2 weeks (Q2W) thereafter up to week 22. From week 14 participants with an inadequate response began treatment with 210 mg brodalumab Q2W. From Week 24 all participants received brodalumab 210 mg Q2W.

    Reporting group title
    Brodalumab 140 mg
    Reporting group description
    Participants received 140 mg brodalumab by subcutaneous injection at baseline, week 1, week 2 and then Q2W thereafter for up to 3 years.

    Reporting group title
    Brodalumab 210 mg
    Reporting group description
    Participants received 210 mg brodalumab by subcutaneous injection at baseline, week 1, week 2 and then Q2W thereafter for up to 3 years.

    Primary: Percentage of Participants with an American College of Rheumatology (ACR) 20 Response at Week 16

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    End point title
    Percentage of Participants with an American College of Rheumatology (ACR) 20 Response at Week 16
    End point description
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of joint pain (measured on a 100 mm VAS); ◦ Patient's Global Assessment (measured on a 100 mm VAS); ◦ Physician Global Assessment of disease activity (measured on a 100 mm VAS); ◦ Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; ◦ C-reactive protein level or erythrocyte sedimentation rate. This endpoint was analyzed in the Primary Analysis Set which consists of all randomized subjects who had the opportunity to complete the week 16 visit prior to termination of the study; Non-responder imputation was used for missing data in the primary analysis.
    End point type
    Primary
    End point timeframe
    Baseline and Week 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: percentage of participants
        number (not applicable)
    24.7
    48.9
    41.8
    Statistical analysis title
    Primary Analysis
    Comparison groups
    Brodalumab 210 mg v Placebo
    Number of subjects included in analysis
    292
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    = 0.0019 [2]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference from placebo
    Point estimate
    17.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.5
         upper limit
    27.7
    Notes
    [1] - To preserve the family-wise 2-sided type 1 error rate at 0.05 for the multiple comparisons of the 2 brodalumab doses with placebo, a sequential testing procedure was used to determine statistical significance for the primary and key secondary endpoints. Nominal P-values are reported.
    [2] - A stratified CMH test adjusting for baseline weight (≤ 100 kg, >100 kg), prior biologic use, and geographic region (North and Latin America, Central/Eastern Europe, Western Europe/Australia).
    Statistical analysis title
    Primary Analysis
    Comparison groups
    Placebo v Brodalumab 140 mg
    Number of subjects included in analysis
    287
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    < 0.0001 [4]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference from placebo
    Point estimate
    24.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    13.5
         upper limit
    35.1
    Notes
    [3] - To preserve the family-wise 2-sided type 1 error rate at 0.05 for the multiple comparisons of the 2 brodalumab doses with placebo, a sequential testing procedure was used to determine statistical significance for the primary and key secondary endpoints. Nominal P-values are reported.
    [4] - A stratified CMH test adjusting for baseline weight (≤100 kg, >100 kg), prior biologic use, and geographic region (North and Latin America, Central/Eastern Europe, Western Europe/Australia).

    Secondary: Percentage of Participants with a 75% or Greater Improvement from Baseline in Psoriasis Area and Severity Index Score (PASI 75) at Week 16

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    End point title
    Percentage of Participants with a 75% or Greater Improvement from Baseline in Psoriasis Area and Severity Index Score (PASI 75) at Week 16
    End point description
    The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0 to 72, with higher scores indicating greater severity and/or more extensive psoriasis. A PASI 75 response is defined as 75% or higher improvement from baseline in PASI score. This analysis was performed on the psoriasis primary efficacy analysis set which consists of those subjects with baseline psoriasis body surface area (BSA) ≥ 3% who were randomized on or before 17 March 2015. Non-responder imputation was used for missing data.
    End point type
    Secondary
    End point timeframe
    Baseline and week 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    108
    92
    106
    Units: percentage of participants
        number (not applicable)
    10.2
    50
    65.1
    Statistical analysis title
    Difference in Response Rate
    Comparison groups
    Placebo v Brodalumab 210 mg
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    superiority [5]
    P-value
    < 0.0001 [6]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference from placebo
    Point estimate
    54.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    44.2
         upper limit
    65.6
    Notes
    [5] - To preserve the family-wise 2-sided type 1 error rate at 0.05 for the multiple comparisons of the 2 brodalumab doses with placebo, a sequential testing procedure was used to determine statistical significance for the primary and key secondary endpoints. Nominal P-values are reported.
    [6] - Stratified CMH test adjusting for baseline weight (≤ 100 kg, >100 kg), prior biologic use yes/no), and geographic region (North and Latin America, Central/Eastern Europe, Western Europe/Australia).
    Statistical analysis title
    Difference in Response rate
    Comparison groups
    Placebo v Brodalumab 140 mg
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    superiority [7]
    P-value
    < 0.0001 [8]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference from placebo
    Point estimate
    39.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    28.1
         upper limit
    51.5
    Notes
    [7] - To preserve the family-wise 2-sided type 1 error rate at 0.05 for the multiple comparisons of the 2 brodalumab doses with placebo, a sequential testing procedure was used to determine statistical significance for the primary and key secondary endpoints. Nominal P-values are reported.
    [8] - Stratified CMH test adjusting for baseline weight (≤ 100 kg, >100 kg), prior biologic use yes/no), and geographic region (North and Latin America, Central/Eastern Europe, Western Europe/Australia).

    Secondary: Change from Baseline in HAQ-DI at Week 16

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    End point title
    Change from Baseline in HAQ-DI at Week 16
    End point description
    The Disability Index of the Health Assessment Questionnaire (HAQ-DI) was utilized to assess the subject’s physical function or disability according to the subject. The HAQ-DI asks about the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores). Responses in each functional area are scored from 0 indicating no difficulty to 3 indicating inability to perform a task in that area. The overall score is the average of each of the 8 category scores and ranges from 0 (no disability) to 3 (very severe, high-dependency disability). The primary analysis set was used for this analysis, subjects with baseline and post-baseline results are included.
    End point type
    Secondary
    End point timeframe
    Baseline and week 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    134
    132
    127
    Units: units on a scale
        least squares mean (standard error)
    -0.167 ± 0.0426
    -0.308 ± 0.0433
    -0.336 ± 0.0431
    Statistical analysis title
    Comparison with Placebo
    Comparison groups
    Placebo v Brodalumab 210 mg
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    superiority [9]
    P-value
    = 0.0023 [10]
    Method
    Mixed effects model repeated measures
    Parameter type
    LS mean difference
    Point estimate
    -0.169
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.278
         upper limit
    -0.061
    Notes
    [9] - To preserve the family-wise 2-sided type 1 error rate at 0.05 for the multiple comparisons of the 2 brodalumab doses with placebo, a sequential testing procedure was used to determine statistical significance for the primary and key secondary endpoints. Nominal P-values are reported.
    [10] - The model includes visit, treatment, treatment by visit and baseline by visit interaction, baseline and baseline weight (≤ 100 kg, >100 kg), prior biologic use, and geographic region.
    Statistical analysis title
    Comparison with Placebo
    Comparison groups
    Placebo v Brodalumab 140 mg
    Number of subjects included in analysis
    266
    Analysis specification
    Pre-specified
    Analysis type
    superiority [11]
    P-value
    = 0.0112 [12]
    Method
    Mixed effects model repeated measures
    Parameter type
    LS mean difference
    Point estimate
    -0.141
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.249
         upper limit
    -0.032
    Notes
    [11] - To preserve the family-wise 2-sided type 1 error rate at 0.05 for the multiple comparisons of the 2 brodalumab doses with placebo, a sequential testing procedure was used to determine statistical significance for the primary and key secondary endpoints. Nominal P-values are reported.
    [12] - The model includes visit, treatment, treatment by visit and baseline by visit interaction, baseline and baseline weight (≤ 100 kg, >100 kg), prior biologic use, and geographic region.

    Secondary: Percentage of Participants with a Psoriasis Symptom Inventory (PSI) response at Week 16

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    End point title
    Percentage of Participants with a Psoriasis Symptom Inventory (PSI) response at Week 16
    End point description
    The Psoriasis Symptom Inventory consists of eight psoriasis-specific items. Participants rated the severity of their symptoms in the last 24 hours on a scale from ‘not at all’ (0) to ‘very severe’ (4) in an electronic diary once a day. Total scores range from 0 to 32 with higher scores indicating worse symptoms. The daily assessment of the Psoriasis Symptom Inventory was analyzed as a weekly average. A PSI response is defined a total score ≤ 8 with no item scores > 1. Analysis was performed in the psoriasis efficacy primary analysis set; non-responder imputation was used.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    104
    82
    99
    Units: percentage of participants
        number (not applicable)
    10.6
    36.6
    53.5
    Statistical analysis title
    Difference in Response Rate
    Comparison groups
    Placebo v Brodalumab 210 mg
    Number of subjects included in analysis
    203
    Analysis specification
    Pre-specified
    Analysis type
    superiority [13]
    P-value
    < 0.0001 [14]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference from placebo
    Point estimate
    43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    31.5
         upper limit
    54.4
    Notes
    [13] - To preserve the family-wise 2-sided type 1 error rate at 0.05 for the multiple comparisons of the 2 brodalumab doses with placebo, a sequential testing procedure was used to determine statistical significance for the primary and key secondary endpoints. Nominal P-values are reported.
    [14] - Stratified CMH test adjusting for baseline weight (≤ 100 kg, >100 kg), prior biologic use yes/no), and geographic region (North and Latin America, Central/Eastern Europe, Western Europe/Australia).
    Statistical analysis title
    Difference in Response Rate
    Comparison groups
    Placebo v Brodalumab 140 mg
    Number of subjects included in analysis
    186
    Analysis specification
    Pre-specified
    Analysis type
    superiority [15]
    P-value
    = 0.0003 [16]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference from placebo
    Point estimate
    26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    14
         upper limit
    38
    Notes
    [15] - To preserve the family-wise 2-sided type 1 error rate at 0.05 for the multiple comparisons of the 2 brodalumab doses with placebo, a sequential testing procedure was used to determine statistical significance for the primary and key secondary endpoints. Nominal P-values are reported.
    [16] - Stratified CMH test adjusting for baseline weight (≤ 100 kg, >100 kg), prior biologic use yes/no), and geographic region (North and Latin America, Central/Eastern Europe, Western Europe/Australia).

    Secondary: Percentage of Participants with an ACR 20 Response by Visit

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    End point title
    Percentage of Participants with an ACR 20 Response by Visit
    End point description
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of joint pain (measured on a 100 mm VAS); ◦ Patient's Global Assessment (measured on a 100 mm VAS); ◦ Physician Global Assessment of disease activity (measured on a 100 mm VAS); ◦ Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; ◦ C-reactive protein level or erythrocyte sedimentation rate. This endpoint was analyzed in the Primary Analysis Set; Non-responder imputation was used for missing data.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8 and 12
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: percentage of participants
    number (not applicable)
        Week 2
    11.6
    17.7
    21.9
        Week 4
    19.2
    27
    38.4
        Week 8
    28.1
    36.2
    45.9
        Week 12
    27.4
    41.8
    47.9
    No statistical analyses for this end point

    Secondary: Change from Baseline in HAQ-DI by Visit

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    End point title
    Change from Baseline in HAQ-DI by Visit
    End point description
    The Disability Index of the Health Assessment Questionnaire (HAQ-DI) was utilized to assess the subject’s physical function or disability according to the subject. The HAQ-DI asks about the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores). Responses in each functional area are scored from 0 indicating no difficulty to 3 indicating inability to perform a task in that area. The overall score is the average of each of the 8 category scores and ranges from 0 (no disability) to 3 (very severe, high-dependency disability). The primary analysis set was used for this analysis; subjects with baseline and post-baseline results are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8 and 12
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: units on a scale
    least squares mean (standard error)
        Week 2 (N = 139, 135, 139)
    -0.129 ± 0.0337
    -0.147 ± 0.0345
    -0.205 ± 0.0338
        Week 4 (N = 137, 135, 139)
    -0.178 ± 0.0377
    -0.244 ± 0.0385
    -0.291 ± 0.0378
        Week 8 (N = 135, 132, 137)
    -0.181 ± 0.0415
    -0.285 ± 0.0423
    -0.313 ± 0.0416
        Week 12 (N = 131, 136, 136)
    -0.208 ± 0.0435
    -0.285 ± 0.0439
    -0.346 ± 0.0435
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a PASI 75 at Each Visit

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    End point title
    Percentage of Participants with a PASI 75 at Each Visit
    End point description
    The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0 to 72, with higher scores indicating greater severity and/or more extensive psoriasis. A PASI 75 response is defined as 75% or higher improvement from baseline in PASI score. This analysis was performed on the psoriasis primary efficacy analysis set which consists of those subjects with baseline psoriasis body surface area (BSA) ≥ 3% who were randomized on or before 17 March 2015. Non-responder imputation was used for missing data.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8 and 12
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    108
    92
    106
    Units: percentage of participants
    number (not applicable)
        Week 2
    1.9
    6.5
    17.9
        Week 4
    5.6
    27.2
    40.6
        Week 8
    7.4
    41.3
    51.9
        Week 12
    11.1
    47.8
    61.3
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a PSI Response at Each Visit

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    End point title
    Percentage of Participants with a PSI Response at Each Visit
    End point description
    The Psoriasis Symptom Inventory consists of eight psoriasis-specific items. Participants rated the severity of their symptoms in the last 24 hours on a scale from ‘not at all’ (0) to ‘very severe’ (4) in an electronic diary once a day. Total scores range from 0 to 32 with higher scores indicating worse symptoms. The daily assessment of the Psoriasis Symptom Inventory was analyzed as a weekly average. A PSI response is defined a total score ≤ 8 with no item scores > 1. Analysis was performed in the psoriasis efficacy primary analysis set; non-responder imputation was used.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 6, 8, 10, and 12
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    104
    82
    99
    Units: percentage of participants
    number (not applicable)
        Week 2
    7.7
    17.1
    21.2
        Week 4
    10.6
    29.3
    47.5
        Week 6
    12.5
    39
    51.5
        Week 8
    13.5
    35.4
    48.5
        Week 10
    13.5
    36.6
    48.5
        Week 12
    13.5
    35.4
    48.5
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an ACR 50 Response by Visit

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    End point title
    Percentage of Participants with an ACR 50 Response by Visit
    End point description
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in tender joint count; • ≥ 50% improvement in swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of joint pain (measured on a 100 mm VAS); ◦ Patient's Global Assessment (measured on a 100 mm VAS); ◦ Physician Global Assessment of disease activity (measured on a 100 mm VAS); ◦ Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; ◦ C-reactive protein level or erythrocyte sedimentation rate. This endpoint was analyzed in the Primary Analysis Set; Non-responder imputation was used for missing data.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12, and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: percentage of participants
    number (not applicable)
        Week 2
    2.7
    1.4
    2.7
        Week 4
    6.2
    11.3
    15.8
        Week 8
    9.6
    17
    17.8
        Week 12
    8.9
    18.4
    24
        Week 16
    8.9
    27.7
    22.6
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an ACR 70 Response by Visit

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    End point title
    Percentage of Participants with an ACR 70 Response by Visit
    End point description
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in tender joint count; • ≥ 70% improvement in swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of joint pain (measured on a 100 mm VAS); ◦ Patient's Global Assessment (measured on a 100 mm VAS); ◦ Physician Global Assessment of disease activity (measured on a 100 mm VAS); ◦ Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; ◦ C-reactive protein level or erythrocyte sedimentation rate. This endpoint was analyzed in the Primary Analysis Set; Non-responder imputation was used for missing data.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: percentage of participants
    number (not applicable)
        Week 2
    0.7
    0
    1.4
        Week 4
    2.1
    2.8
    4.8
        Week 8
    4.8
    5
    8.9
        Week 12
    2.1
    9.2
    10.3
        Week 16
    3.4
    12.8
    10.3
    No statistical analyses for this end point

    Secondary: Change from Baseline in Tender Joint Count

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    End point title
    Change from Baseline in Tender Joint Count
    End point description
    A total of 68 joints were scored for the presence or absence of tenderness by an experienced, independent and blinded joint evaluator. Analysis was performed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: joints
    least squares mean (standard error)
        Week 2 (N = 144, 137, 138)
    -2.289 ± 0.7523
    -2.627 ± 0.7704
    -3.518 ± 0.7646
        Week 4 (N = 140, 138, 139)
    -4.45 ± 0.899
    -3.679 ± 0.9139
    -6.472 ± 0.908
        Week 8 (N = 138, 136, 137)
    -5.078 ± 0.9601
    -6.037 ± 0.9769
    -7.042 ± 0.9697
        Week 12 (N = 133, 137, 135)
    -4.803 ± 1.0081
    -6.071 ± 1.0182
    -8.443 ± 1.0147
        Week 16 (N = 135, 131, 130)
    -3.57 ± 1.0656
    -7.596 ± 1.0841
    -7.987 ± 1.0803
    No statistical analyses for this end point

    Secondary: Change from Baseline in Swollen Joint Count

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    End point title
    Change from Baseline in Swollen Joint Count
    End point description
    A total of 66 joints were scored for the presence or absence of swelling by an experienced, independent and blindedjoint evaluator. Analysis was performed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: joints
    least squares mean (standard error)
        Week 2 (N = 144, 137, 138)
    -2.13 ± 0.5097
    -2.711 ± 0.5231
    -2.438 ± 0.5186
        Week 4 (N = 140, 138, 139)
    -2.931 ± 0.5381
    -3.49 ± 0.5483
    -4.495 ± 0.543
        Week 8 (N = 138, 136, 137)
    -3.643 ± 0.5874
    -5.316 ± 0.5985
    -5.301 ± 0.5926
        Week 12 (N = 133, 137, 135)
    -3.175 ± 0.618
    -5.754 ± 0.6256
    -5.946 ± 0.6216
        Week 16 (N = 135, 130, 131)
    -2.454 ± 0.6601
    -6.569 ± 0.6726
    -6.157 ± 0.6687
    No statistical analyses for this end point

    Secondary: Change from Baseline in Patient Global Assessment of Joint Pain

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    End point title
    Change from Baseline in Patient Global Assessment of Joint Pain
    End point description
    The severity of the subject’s joint pain was assessed on a 100 mm visual analog scale. The subject drew a vertical line through a horizontal line to indicate how much pain they were experiencing “today” on a scale from 0 (No Pain At All) on the left and 100 (Worst Pain Imaginable) on the right end of the line. Analysis was performed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: mm
    least squares mean (standard error)
        Week 2 (N = 139, 135, 139)
    -0.705 ± 1.8273
    -3.111 ± 1.8652
    -5.204 ± 1.8274
        Week 4 (N = 137, 135, 139)
    -1.28 ± 1.9124
    -3.654 ± 1.9506
    -9.303 ± 1.9182
        Week 8 (N = 135, 132, 137)
    -0.698 ± 2.0958
    -7.17 ± 2.1375
    -8.353 ± 2.1011
        Week 12 (N = 131, 136, 136)
    0.03 ± 2.1127
    -6.317 ± 2.1315
    -11.07 ± 2.1122
        Week 16 (N = 134, 132, 127)
    0.273 ± 2.1495
    -9.816 ± 2.1865
    -11.13 ± 2.1804
    No statistical analyses for this end point

    Secondary: Change from Baseline in Patient Global Assessment of Arthritis Activity

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    End point title
    Change from Baseline in Patient Global Assessment of Arthritis Activity
    End point description
    The subject’s global assessment of his or her arthritis disease activity was assessed by completion of a 100 mm visual analog scale. The subject drew a vertical line through a horizontal line to indicate how they are doing based on all the ways their arthritis affects them at the time of completion, with a scale from 0 (Very Well) on the left to 100 (Very Poorly) on the right end of the line. Analysis was performed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: mm
    least squares mean (standard error)
        Week 2 (N = 139, 135, 139)
    -1.473 ± 1.779
    -6.673 ± 1.8189
    -6.752 ± 1.7792
        Week 4 (N = 137, 135, 139)
    -2.789 ± 1.9229
    -6.435 ± 1.9622
    -11.39 ± 1.9285
        Week 8 (N = 135, 132, 137)
    -2.731 ± 2.0658
    -11.22 ± 2.1093
    -10.96 ± 2.0729
        Week 12 (N = 131, 136, 136)
    -2.064 ± 2.0462
    -10.38 ± 2.0656
    -13.3 ± 2.0457
        Week 16 (N = 134, 132, 127)
    -1.472 ± 2.1119
    -12.33 ± 2.1507
    -14.05 ± 2.1458
    No statistical analyses for this end point

    Secondary: Change from Baseline in Physician Global Assessment of Arthritis Activity

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    End point title
    Change from Baseline in Physician Global Assessment of Arthritis Activity
    End point description
    The physician's global assessment of subjects' arthritis disease activity was assessed on a 100 mm visual analog scale from 0 (Very Well ) to 100 (Very Poorly). Analysis was performed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: mm
    least squares mean (standard error)
        Week 2 (N = 138, 131, 137)
    -7.317 ± 1.7275
    -13.38 ± 1.7918
    -15.6 ± 1.7375
        Week 4 (N = 134, 131, 140)
    -10.4 ± 1.8609
    -14.35 ± 1.9169
    -21.69 ± 1.854
        Week 8 (N = 133, 127, 137)
    -11.41 ± 1.9231
    -21.22 ± 1.9934
    -24.08 ± 1.9276
        Week 12 (N = 128, 133, 136)
    -9.653 ± 2.0172
    -22.33 ± 2.0505
    -26.69 ± 2.0064
        Week 16 (N = 131, 128, 127)
    -11.45 ± 2.1523
    -23.88 ± 2.2099
    -26.88 ± 2.1775
    No statistical analyses for this end point

    Secondary: Change from Baseline in Erythrocyte Sedimentation Rate

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    End point title
    Change from Baseline in Erythrocyte Sedimentation Rate
    End point description
    Analysis was performed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: mm/hr
    arithmetic mean (standard deviation)
        Week 2 (N = 134, 132, 132)
    -1.9 ± 15.07
    -3 ± 10.5
    -1.3 ± 13.51
        Week 4 (N = 132, 134, 135)
    -1.3 ± 17.73
    -1.6 ± 14.7
    -3.7 ± 15.18
        Week 8 (N = 131, 131, 134)
    0.8 ± 18.55
    -3.9 ± 16.9
    -4.9 ± 13.87
        Week 12 (N = 127, 134, 131)
    -1 ± 17.79
    -4 ± 15.64
    -5.7 ± 17.72
        Week 16 (N = 128, 128, 124)
    -0.6 ± 18.08
    -3.9 ± 15.7
    -6.8 ± 17.9
    No statistical analyses for this end point

    Secondary: Change from Baseline in C-Reactive Protein (CRP)

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    End point title
    Change from Baseline in C-Reactive Protein (CRP)
    End point description
    Analysis was performed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: mg/L
    arithmetic mean (standard deviation)
        Week 2 (N = 140, 136, 138)
    -0.38 ± 7.799
    -1.33 ± 20.432
    -2.37 ± 10.081
        Week 4 (N = 139, 136, 138)
    0.26 ± 11.678
    -0.84 ± 13.966
    -2.26 ± 11.96
        Week 8 (N = 136, 135, 137)
    0.77 ± 9.939
    -2.51 ± 11.142
    -2.25 ± 13.005
        Week 12 (N = 132, 137, 134)
    0.42 ± 10.148
    -2.21 ± 11.308
    -1.92 ± 11.96
        Week 16 (N = 134, 131, 129)
    0.14 ± 10.812
    -1.4 ± 12.554
    -2.83 ± 11.969
    No statistical analyses for this end point

    Secondary: Change from Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP)

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    End point title
    Change from Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP)
    End point description
    The DAS28-CRP is a composite score to measure disease activity in patients with arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • C-reactive protein (CRP) level; • Patient's global assessment of disease activity assessed on a VAS from 0 to 100. The DAS28-CRP score ranges from approximately zero to ten. Higher DAS28-CRP scores indicate higher disease activity. Analysis was performed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: units on a scale
    least squares mean (standard error)
        Week 2 (N = 136, 132, 132)
    -0.213 ± 0.0739
    -0.511 ± 0.076
    -0.541 ± 0.0751
        Week 4 (N = 134, 133, 132)
    -0.408 ± 0.0858
    -0.651 ± 0.0876
    -0.94 ± 0.087
        Week 8 (N = 133, 132, 134)
    -0.497 ± 0.0964
    -1.013 ± 0.0983
    -1.018 ± 0.0973
        Week 12 (N = 130, 136, 132)
    -0.506 ± 0.1006
    -1.013 ± 0.1015
    -1.182 ± 0.1013
        Week 16 (N = 133, 131, 126)
    -0.332 ± 0.1061
    -1.179 ± 0.108
    -1.147 ± 0.1081
    No statistical analyses for this end point

    Secondary: Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

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    End point title
    Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
    End point description
    BASDAI is a self-administered questionnaire composed of six items using an 11-point numerical rating scale from “0 = none” to “10 = very severe” for the first five items, and “0 = 0 hours” to “10 = 2 or more hours” for the sixth item that asks about the duration of morning stiffness. The BASDAI assesses the severity of fatigue, spinal and peripheral joint pain, localized tenderness, and morning stiffness. The final BASDAI score averages the individual assessments for a final score range of 0-10. Analyzed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: units on a scale
    least squares mean (standard error)
        Week 12 (N = 130, 135, 136)
    -0.318 ± 0.1747
    -0.952 ± 0.1765
    -1.295 ± 0.1757
        Week 16 (N = 134, 132, 127)
    -0.34 ± 0.1694
    -1.113 ± 0.1738
    -1.337 ± 0.1739
    No statistical analyses for this end point

    Secondary: Change from Baseline in Dactylitis Score

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    End point title
    Change from Baseline in Dactylitis Score
    End point description
    Dactylitis was assessed for presence or absence on 20 digits (fingers and toes) by an independent assessor. The dactylitis count is defined as the sum of 20 fingers/toes that exhibit dactylitis (absent 0, present 1). Analysis was performed in the primary analysis set; only subjects with baseline dactylitis count > 0 and post-baseline results are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: digits
    least squares mean (standard error)
        Week 4 (N = 70, 52, 69)
    -1.019 ± 0.3962
    -1.327 ± 0.437
    -2.018 ± 0.3844
        Week 12 (N = 65, 50, 66)
    -1.057 ± 0.4232
    -2.278 ± 0.4654
    -2.31 ± 0.4105
        Week 16 (N = 65, 48, 63)
    -1.156 ± 0.4303
    -3.158 ± 0.4783
    -2.857 ± 0.4219
    No statistical analyses for this end point

    Secondary: Change from Baseline in Enthesitis Count

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    End point title
    Change from Baseline in Enthesitis Count
    End point description
    Enthesitis was assessed for presence or absence on 6 entheses by an independent assessor. The sites assessed were: Lateral epicondyle (left/right), Medial femoral condyle (left/right), Achilles tendon insertion (left/right). The enthesitis count is defined as the total number of 6 sites that have enthesitis. Analysis was performed in the primary analysis set; subjects with baseline enthesitis > 0 and post-baseline results are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 4, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: entheses
    least squares mean (standard error)
        Week 4 (N = 88, 77, 87)
    -0.875 ± 0.1718
    -0.831 ± 0.1752
    -0.845 ± 0.1716
        Week 12 (N = 82, 76, 84)
    -0.713 ± 0.1911
    -1.245 ± 0.1944
    -1.087 ± 0.1888
        Week 16 (N = 81, 72, 81)
    -0.76 ± 0.1999
    -1.283 ± 0.2065
    -1.106 ± 0.1981
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a PASI 90 Response

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    End point title
    Percentage of Participants with a PASI 90 Response
    End point description
    A PASI 90 response is a 90% or greater improvement (reduction) from baseline in PASI score. The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0 to 72, with higher scores indicating greater severity and/or more extensive psoriasis. This analysis was performed on the psoriasis primary efficacy analysis set; Non-responder imputation was used for missing data.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12, and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    108
    92
    106
    Units: percentage of participants
    number (not applicable)
        Week 2
    0
    2.2
    6.6
        Week 4
    2.8
    13
    23.6
        Week 8
    2.8
    25
    35.8
        Week 12
    4.6
    33.7
    42.5
        Week 16
    5.6
    34.8
    46.2
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a PASI 100 Response

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    End point title
    Percentage of Participants with a PASI 100 Response
    End point description
    A PASI 100 response is a 100% improvement (reduction) from baseline in PASI score. The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0 to 72, with higher scores indicating greater severity and/or more extensive psoriasis. This analysis was performed on the psoriasis primary efficacy analysis set; Non-responder imputation was used for missing data.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    108
    92
    106
    Units: percentage of participants
    number (not applicable)
        Week 2
    0
    0
    2.8
        Week 4
    0
    4.3
    14.2
        Week 8
    2.8
    13
    27.4
        Week 12
    4.6
    16.3
    32.1
        Week 16
    3.7
    19.6
    34
    No statistical analyses for this end point

    Secondary: Percent Change from Baseline in PASI Score

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    End point title
    Percent Change from Baseline in PASI Score
    End point description
    The PASI measures the average redness (erythema), thickness (induration), and scaliness (each graded on a 0 to 4 scale) of psoriasis lesions, weighted by the area of involvement in the four main body areas (i.e., head and neck, trunk, upper extremities, and lower extremities). PASI scores can range from 0 to 72, with higher scores indicating greater severity and/or more extensive psoriasis. This analysis was performed on the psoriasis primary efficacy analysis set; subjects with baseline and post-baseline results are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    108
    92
    106
    Units: percent change
    arithmetic mean (standard deviation)
        Week 2 (N = 107, 90, 101)
    -6.36 ± 29.106
    -29.68 ± 50.269
    -38.67 ± 37.624
        Week 4 (N = 104, 90, 104)
    -12.33 ± 42.758
    -47.08 ± 44.93
    -60.33 ± 34.341
        Week 8 (N = 104, 88, 101)
    -8.21 ± 66.319
    -48.58 ± 68.894
    -64.64 ± 48.277
        Week 12 (N = 98, 89, 101)
    -11.8 ± 69.071
    -49.64 ± 87.796
    -68.32 ± 50.633
        Week 16 (N=100, 84, 97)
    -8.18 ± 60.382
    -46.08 ± 88.738
    -69.86 ± 55.772
    No statistical analyses for this end point

    Secondary: Percentage of Body Surface Area (BSA) Involved With Psoriasis

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    End point title
    Percentage of Body Surface Area (BSA) Involved With Psoriasis
    End point description
    A measurement of psoriasis involvement, given as the assessor’s assessment of the proportion of the subject’s total body surface area involved with psoriasis. This analysis was performed on the psoriasis primary efficacy analysis set; subjects with baseline and post-baseline results are included.
    End point type
    Secondary
    End point timeframe
    Weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    108
    92
    106
    Units: percent
    least squares mean (standard error)
        Week 2 (N = 107, 90, 101)
    17.702 ± 0.817
    15.242 ± 0.884
    12.667 ± 0.8486
        Week 4 (N = 104, 90, 104)
    16.29 ± 1.0103
    10.834 ± 1.0915
    8.477 ± 1.0328
        Week 8 (N = 104, 88, 101)
    16.843 ± 1.053
    9.546 ± 1.1421
    6.643 ± 1.0773
        Week 12 (N = 98, 88, 101)
    15.862 ± 1.0848
    8.224 ± 1.172
    5.271 ± 1.105
        Week 16 (N = 99, 84, 97)
    16.405 ± 1.1032
    7.841 ± 1.1956
    4.196 ± 1.126
    No statistical analyses for this end point

    Secondary: Nail Psoriasis Severity Index (NAPSI) Score

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    End point title
    Nail Psoriasis Severity Index (NAPSI) Score
    End point description
    The NAPSI scale is an objective, numeric, and reproducible grading system for nail psoriasis that incorporates the many different features of nail psoriasis. Each quarter of the nail was scored for the presence (1) or absence (0) of 8 clinical features for a score of 0-4 for each feature. The total score for each nail ranges from 0 (absent) to 32 (worst). Results are reported for the primary analysis set for the worst nail for subjects with baseline NAPSI score ≥ 6 and post-baseline results.
    End point type
    Secondary
    End point timeframe
    Weeks 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: units on a scale
    least squares mean (standard error)
        Week 12 (N = 46, 58, 60)
    8.228 ± 0.6333
    5.879 ± 0.6016
    5.394 ± 0.6167
        Week 16 (N = 47, 55, 58)
    8.151 ± 0.6554
    5.098 ± 0.6312
    4.663 ± 0.6413
    No statistical analyses for this end point

    Secondary: Change from Baseline in Clinical Disease Activity Index (CDAI)

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    End point title
    Change from Baseline in Clinical Disease Activity Index (CDAI)
    End point description
    The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician's Global Assessment of Disease Activity - measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. This analysis was performed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: units on a scale
    least squares mean (standard error)
        Week 2 (N = 136, 130, 134)
    -2.93 ± 0.7645
    -5.555 ± 0.7928
    -6.085 ± 0.7728
        Week 4 (N = 133, 131, 136)
    -5.571 ± 0.8705
    -6.681 ± 0.8971
    -10.02 ± 0.8728
        Week 8 (N = 133, 127, 135)
    -6.135 ± 0.977
    -10.4 ± 1.0014
    -10.31 ± 0.9806
        Week 12 (N = 128, 133, 135)
    -5.694 ± 0.9849
    -10.6 ± 1.0046
    -12.27 ± 0.9826
        Week 16 (N = 132, 128, 127)
    -4.443 ± 1.0628
    -12.11 ± 1.0939
    -11.9 ± 1.0764
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Psoriatic Arthritis Response Criteria (PsARC) Response

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    End point title
    Percentage of Participants with a Psoriatic Arthritis Response Criteria (PsARC) Response
    End point description
    A PsARC response is defined as improvement in at least 2 of the following 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • Tender joint count, • Swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening is defined as decrease or increase, respectively, from baseline by ≥ 30%. Analysis was performed in the psoriasis efficacy primary analysis set; non-responder imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: percentage of participants
    number (not applicable)
        Week 2
    23.3
    36.2
    36.3
        Week 4
    32.2
    44.7
    58.9
        Week 8
    39
    56.7
    55.5
        Week 12
    41.1
    57.4
    63
        Week 16
    34.9
    59.6
    59.6
    No statistical analyses for this end point

    Secondary: Psoriatic Arthritis Disease Activity Score (PASDAS)

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    End point title
    Psoriatic Arthritis Disease Activity Score (PASDAS)
    End point description
    The Psoriatic Arthritis Disease Activity Score consists of the following domains: tender joint count, swollen joint count, physician and patient global assessment of arthritis and skin, dactylitis, enthesitis, CRP and Medical Outcomes Survey Short form-36 (SF-36) physical component summary. The index score is calculated from each component using weighted coefficients; the total score ranges from approximately 0 to 10, where lower scores represent less disease activity. This analysis was performed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Weeks 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: units on a scale
    least squares mean (standard error)
        Week 12 (N = 124, 131, 131)
    5.405 ± 0.1367
    4.54 ± 0.1395
    4.262 ± 0.1377
        Week 16 (N = 128, 128, 126)
    5.442 ± 0.144
    4.361 ± 0.148
    4.098 ± 0.1464
    No statistical analyses for this end point

    Secondary: Change from Baseline in Dermatology Life Quality Index (DLQI)

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    End point title
    Change from Baseline in Dermatology Life Quality Index (DLQI)
    End point description
    The dermatology life quality index (DLQI) is a skin disease-specific instrument to evaluate health-related quality of life. The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answered 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is from 0 (best possible score) to 30 (worst possible score). Analyzed in the primary analysis set; subjects with baseline and post-baseline results at each time point are included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: units on a scale
    least squares mean (standard error)
        Week 2 (N = 139, 135, 139)
    -1.442 ± 0.3739
    -3.716 ± 0.3825
    -4.461 ± 0.3748
        Week 4 (N = 137, 135, 139)
    -2.282 ± 0.3797
    -5.24 ± 0.3884
    -5.742 ± 0.3815
        Week 8 (N = 135, 132, 137)
    -1.814 ± 0.4356
    -5.836 ± 0.4445
    -6.04 ± 0.4367
        Week 12 (N = 131, 136, 136)
    -1.857 ± 0.4248
    -5.587 ± 0.4304
    -6.368 ± 0.4253
        Week 16 (N = 134, 132, 127)
    -1.698 ± 0.4392
    -5.537 ± 0.4475
    -6.541 ± 0.4445
    No statistical analyses for this end point

    Secondary: Change from Baseline in Medical Outcomes Short Form-36 (SF-36) Mental and Physical Component Scores

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    End point title
    Change from Baseline in Medical Outcomes Short Form-36 (SF-36) Mental and Physical Component Scores
    End point description
    The SF-36 assesses the general quality of life of participants by evaluating the domains of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The questionnaire consists of 36 questions that are completed by the participant. The individual domain scores are aggregated to derive a physical-component summary score and a mental-component summary score which range from 0 to 100, with higher scores indicating a better level of functioning. This analysis was performed in the primary analysis set; subjects with baseline and post-baseline results at each time point were included.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: units on a scale
    least squares mean (standard error)
        Physical component: Week 12 (N = 130, 135, 136)
    1.635 ± 0.7033
    4.134 ± 0.7149
    3.724 ± 0.7084
        Physical component: Week 16 (N = 134, 132, 127)
    1.313 ± 0.6958
    4.632 ± 0.7183
    4.887 ± 0.7156
        Mental component: week 12 (N = 130, 135, 136)
    3.571 ± 0.7081
    5.125 ± 0.7158
    5.524 ± 0.7107
        Mental component: Week 16 (N = 134, 132, 127)
    3.869 ± 0.7123
    5.05 ± 0.7319
    5.919 ± 0.7315
    No statistical analyses for this end point

    Secondary: Work Productivity and Activity Impairment (WPAI)

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    End point title
    Work Productivity and Activity Impairment (WPAI)
    End point description
    The WPAI is a 6-item generic questionnaire assessing the subject’s work productivity and activity impairment due to a given condition. The generic version of the questionnaire can be customized to specific health conditions such as psoriatic arthritis (ie, WPAI-Psoratic Arthritis) by specifying the health condition of interest as psoriatic arthritis in the questions. The WPAI assesses the subject’s work time missed (absenteeism), impairment at work or reduced on-the-job effectiveness (presenteeism), overall work impairment (abseentism and presenteeism, ie, work productivity loss), and activity impairment outside the work environment. The WPAI outcomes are expressed as impairment percentages whereby higher scores indicate greater impairment and less productivity (ie, worse outcomes). Analyzed in the primary analysis set; the first 3 scores only include subjects who were employed at that time point.
    End point type
    Secondary
    End point timeframe
    Weeks 12 and 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    146
    141
    146
    Units: percent impairment
    arithmetic mean (standard deviation)
        Absenteeism: Baseline (N = 88, 86, 97)
    13.77 ± 27.804
    10.76 ± 22.532
    8.47 ± 19.438
        Absenteeism: Week 12 (N = 79, 85, 94)
    6.19 ± 16.496
    5.93 ± 19.419
    3.39 ± 12.726
        Absenteeism: Week 16 (N = 76, 82, 89)
    4.75 ± 14.995
    7.74 ± 21.162
    4.74 ± 16.456
        Presenteeism:Baseline (N = 83, 82, 95)
    39.64 ± 25.349
    38.05 ± 24.966
    40.63 ± 26.61
        Presenteeism:Week 12 (N = 78, 82, 93)
    29.23 ± 25.724
    25.73 ± 22.445
    22.26 ± 21.975
        Presenteeism:Week 16 (N = 75, 79, 87)
    28.53 ± 25.611
    23.8 ± 23
    22.76 ± 20.442
        Work impairment: Baseline (N = 83, 82, 95)
    43.29 ± 27.507
    41.03 ± 26.245
    43.3 ± 28.483
        Work impairment: Week 12 (N = 78, 82, 93)
    31.52 ± 28.267
    26.93 ± 23.676
    23.53 ± 23.32
        Work impairment: Week 16 (N = 75, 79, 87)
    30.17 ± 26.685
    26.58 ± 24.856
    24.34 ± 21.99
        Activity Impairment: Baseline (N = 145, 141, 145)
    45.17 ± 24.752
    44.11 ± 26.701
    46.21 ± 25.306
        Activity Impairment: Week 12 (N = 131, 135, 137)
    36.41 ± 24.809
    32.15 ± 25.227
    29.34 ± 25.987
        Activity Impairment: Week 16 (N = 135, 132, 128)
    38.89 ± 25.294
    29.32 ± 24.187
    29.84 ± 23.876
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of Brodalumab at Week 16

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    End point title
    Plasma Concentrations of Brodalumab at Week 16
    End point description
    Plasma concentrations are calculated using log-transformed data from subjects with measurable levels > lower limit of quantitation (LLQ) of 50 ng/mL
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    0 [17]
    68
    101
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    ±
    2172 ± 395.4
    5746 ± 414.4
    Notes
    [17] - Subjects did not receive brodalumab
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until 30 days after last dose; up to 162 weeks
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received placebo subcutaneous injection at baseline, week 1, week 2 and then every 2 weeks (Q2W) thereafter up to week 22. From week 14 participants with an inadequate response began treatment with 210 mg brodalumab Q2W. From Week 24 all participants received brodalumab 210 mg Q2W.

    Reporting group title
    Brodalumab 210 mg Q2W
    Reporting group description
    Participants received 210 mg brodalumab by subcutaneous injection at baseline, week 1, week 2 and then Q2W thereafter for up to 3 years.

    Reporting group title
    Brodalumab 140 mg Q2W
    Reporting group description
    Participants received 140 mg brodalumab by subcutaneous injection at baseline, week 1, week 2 and then Q2W thereafter for up to 3 years.

    Serious adverse events
    Placebo Brodalumab 210 mg Q2W Brodalumab 140 mg Q2W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 161 (7.45%)
    7 / 163 (4.29%)
    8 / 160 (5.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Abortion induced
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 161 (0.62%)
    2 / 163 (1.23%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary artery disease
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dressler's syndrome
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid artery stenosis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Leukoplakia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psoriasis
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bursitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psoriatic arthropathy
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Skin infection
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Placebo Brodalumab 210 mg Q2W Brodalumab 140 mg Q2W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    123 / 161 (76.40%)
    114 / 163 (69.94%)
    106 / 160 (66.25%)
    Injury, poisoning and procedural complications
    Animal scratch
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    0
    0
    2
    Ankle fracture
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Arthropod bite
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 163 (1.23%)
    1 / 160 (0.63%)
         occurrences all number
    0
    2
    1
    Arthropod sting
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    1
    1
    0
    Contusion
         subjects affected / exposed
    3 / 161 (1.86%)
    4 / 163 (2.45%)
    4 / 160 (2.50%)
         occurrences all number
    6
    4
    7
    Eye contusion
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    2
    0
    1
    Eye injury
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Face injury
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Fall
         subjects affected / exposed
    3 / 161 (1.86%)
    2 / 163 (1.23%)
    2 / 160 (1.25%)
         occurrences all number
    4
    2
    2
    Foot fracture
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Joint capsule rupture
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    2
    0
    0
    Joint injury
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Laceration
         subjects affected / exposed
    1 / 161 (0.62%)
    2 / 163 (1.23%)
    0 / 160 (0.00%)
         occurrences all number
    1
    3
    0
    Ligament sprain
         subjects affected / exposed
    2 / 161 (1.24%)
    3 / 163 (1.84%)
    0 / 160 (0.00%)
         occurrences all number
    3
    4
    0
    Limb injury
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    0
    0
    2
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Meniscus injury
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    0
    0
    2
    Muscle strain
         subjects affected / exposed
    2 / 161 (1.24%)
    2 / 163 (1.23%)
    1 / 160 (0.63%)
         occurrences all number
    3
    2
    1
    Post-traumatic pain
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Procedural pain
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Road traffic accident
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Skin abrasion
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    1
    1
    1
    Splinter
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Sternal fracture
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Tendon rupture
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Thermal burn
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Tooth fracture
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    1
    1
    0
    Wound
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    1
    0
    2
    Wrist fracture
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 161 (1.24%)
    2 / 163 (1.23%)
    2 / 160 (1.25%)
         occurrences all number
    2
    2
    3
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 161 (1.86%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    4
    0
    2
    Blood cholesterol increased
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Blood glucose decreased
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Blood glucose increased
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    1
    1
    1
    Blood potassium increased
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Blood pressure increased
         subjects affected / exposed
    1 / 161 (0.62%)
    2 / 163 (1.23%)
    2 / 160 (1.25%)
         occurrences all number
    1
    2
    2
    Blood triglycerides increased
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Colonoscopy
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Heart rate increased
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Hepatic enzyme abnormal
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    2
    Lipids abnormal
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Liver function test abnormal
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Low density lipoprotein increased
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    2
    0
    0
    Lymphocyte count increased
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Mammogram abnormal
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Monocyte count increased
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    3
    Neutrophil count increased
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    1
    1
    0
    Platelet count decreased
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Thyroid gland scan abnormal
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Transaminases increased
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Vitamin D decreased
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 163 (1.23%)
    0 / 160 (0.00%)
         occurrences all number
    0
    2
    0
    Weight decreased
         subjects affected / exposed
    3 / 161 (1.86%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    4
    0
    1
    Weight increased
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 163 (1.23%)
    1 / 160 (0.63%)
         occurrences all number
    0
    3
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    0
    0
    3
    White blood cell count increased
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    1
    1
    0
    White blood cells urine positive
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Cardiac disorders
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Coronary artery disease
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Palpitations
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Leukocytosis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Leukopenia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    2
    1
    Lymphadenopathy
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Lymphatic disorder
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Lymphopenia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Neutropenia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Thrombocytopenia
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Anosmia
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Burning sensation
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    0
    0
    2
    Dizziness
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    3 / 160 (1.88%)
         occurrences all number
    3
    1
    3
    Dizziness postural
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Headache
         subjects affected / exposed
    11 / 161 (6.83%)
    4 / 163 (2.45%)
    5 / 160 (3.13%)
         occurrences all number
    11
    5
    6
    Hypertensive encephalopathy
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Hypoaesthesia
         subjects affected / exposed
    3 / 161 (1.86%)
    2 / 163 (1.23%)
    2 / 160 (1.25%)
         occurrences all number
    3
    3
    2
    Intercostal neuralgia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Loss of consciousness
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Lumbar radiculopathy
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Migraine
         subjects affected / exposed
    1 / 161 (0.62%)
    3 / 163 (1.84%)
    0 / 160 (0.00%)
         occurrences all number
    3
    4
    0
    Nerve compression
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Nerve root compression
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Neuralgia
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 163 (1.23%)
    0 / 160 (0.00%)
         occurrences all number
    0
    2
    0
    Paraesthesia
         subjects affected / exposed
    3 / 161 (1.86%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    3
    0
    0
    Parkinson's disease
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Polyneuropathy
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Radiculopathy
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    2
    0
    0
    Sciatica
         subjects affected / exposed
    2 / 161 (1.24%)
    2 / 163 (1.23%)
    1 / 160 (0.63%)
         occurrences all number
    2
    2
    1
    Sinus headache
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Syncope
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    2
    1
    0
    Tarsal tunnel syndrome
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Tremor
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Vocal cord paresis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Eye disorders
    Blepharitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    2 / 160 (1.25%)
         occurrences all number
    0
    1
    2
    Blepharitis allergic
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Blepharospasm
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Cataract
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    0
    0
    2
    Chalazion
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Conjunctival hyperaemia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Dry eye
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    1
    0
    2
    Eye allergy
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Eye irritation
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Eye pain
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Eye pruritus
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    1
    1
    0
    Fuchs' syndrome
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Glaucoma
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Uveitis
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    2
    Vision blurred
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Visual acuity reduced
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Visual impairment
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    2
    0
    Vitreous degeneration
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Vitreous floaters
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Ear pain
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    2 / 160 (1.25%)
         occurrences all number
    1
    1
    3
    External ear inflammation
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    1
    1
    0
    Paraesthesia ear
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Tinnitus
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Vertigo
         subjects affected / exposed
    2 / 161 (1.24%)
    3 / 163 (1.84%)
    0 / 160 (0.00%)
         occurrences all number
    2
    3
    0
    Vertigo labyrinthine
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Abdominal hernia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Abdominal pain
         subjects affected / exposed
    4 / 161 (2.48%)
    3 / 163 (1.84%)
    0 / 160 (0.00%)
         occurrences all number
    4
    4
    0
    Abdominal pain upper
         subjects affected / exposed
    4 / 161 (2.48%)
    2 / 163 (1.23%)
    1 / 160 (0.63%)
         occurrences all number
    4
    2
    3
    Abdominal rigidity
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Abdominal tenderness
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    2
    0
    0
    Aphthous ulcer
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    2 / 160 (1.25%)
         occurrences all number
    0
    1
    2
    Colitis ulcerative
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    2
    0
    Constipation
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    2
    1
    1
    Diarrhoea
         subjects affected / exposed
    15 / 161 (9.32%)
    12 / 163 (7.36%)
    5 / 160 (3.13%)
         occurrences all number
    22
    13
    6
    Diverticulum intestinal
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Dry mouth
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    2
    1
    Dyspepsia
         subjects affected / exposed
    4 / 161 (2.48%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    4
    0
    1
    Dysphagia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Faeces discoloured
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Flatulence
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    1
    1
    0
    Gastritis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal telangiectasia
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    5 / 161 (3.11%)
    4 / 163 (2.45%)
    2 / 160 (1.25%)
         occurrences all number
    5
    4
    2
    Gingival atrophy
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    2
    0
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Haemorrhoids thrombosed
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Nausea
         subjects affected / exposed
    10 / 161 (6.21%)
    7 / 163 (4.29%)
    5 / 160 (3.13%)
         occurrences all number
    14
    7
    8
    Oesophageal ulcer
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Oesophagitis
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Oral discomfort
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Salivary gland disorder
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Toothache
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Umbilical hernia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Vomiting
         subjects affected / exposed
    7 / 161 (4.35%)
    2 / 163 (1.23%)
    2 / 160 (1.25%)
         occurrences all number
    10
    2
    3
    Renal and urinary disorders
    Diabetic nephropathy
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Dysuria
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Nephritis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Nephrolithiasis
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    1
    1
    1
    Nephroptosis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Polyuria
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Renal cyst
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Renal failure
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Anhidrosis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Blister
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Decubitus ulcer
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Dermatitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Dermatitis acneiform
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Dermatitis allergic
         subjects affected / exposed
    1 / 161 (0.62%)
    2 / 163 (1.23%)
    0 / 160 (0.00%)
         occurrences all number
    1
    4
    0
    Dermatitis contact
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    2
    1
    1
    Diffuse alopecia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Dry skin
         subjects affected / exposed
    1 / 161 (0.62%)
    2 / 163 (1.23%)
    2 / 160 (1.25%)
         occurrences all number
    1
    2
    4
    Dyshidrotic eczema
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Eczema
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    1
    1
    0
    Erythema
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    2 / 160 (1.25%)
         occurrences all number
    1
    1
    2
    Guttate psoriasis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Hyperkeratosis
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    1
    1
    1
    Intertrigo
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 163 (1.23%)
    2 / 160 (1.25%)
         occurrences all number
    0
    2
    2
    Nail psoriasis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Pain of skin
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Papule
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Photosensitivity reaction
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Pruritus
         subjects affected / exposed
    7 / 161 (4.35%)
    2 / 163 (1.23%)
    4 / 160 (2.50%)
         occurrences all number
    9
    2
    4
    Psoriasis
         subjects affected / exposed
    6 / 161 (3.73%)
    2 / 163 (1.23%)
    4 / 160 (2.50%)
         occurrences all number
    6
    2
    6
    Rash
         subjects affected / exposed
    4 / 161 (2.48%)
    5 / 163 (3.07%)
    3 / 160 (1.88%)
         occurrences all number
    4
    7
    3
    Rash macular
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Rosacea
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    2
    1
    0
    Skin lesion
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    0
    0
    2
    Skin mass
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Splinter haemorrhages
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Swelling face
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Urticaria
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    2
    1
    0
    Xeroderma
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    10 / 161 (6.21%)
    5 / 163 (3.07%)
    6 / 160 (3.75%)
         occurrences all number
    11
    5
    6
    Arthritis
         subjects affected / exposed
    4 / 161 (2.48%)
    2 / 163 (1.23%)
    2 / 160 (1.25%)
         occurrences all number
    5
    2
    2
    Back pain
         subjects affected / exposed
    9 / 161 (5.59%)
    4 / 163 (2.45%)
    4 / 160 (2.50%)
         occurrences all number
    9
    4
    4
    Bone pain
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 163 (1.23%)
    0 / 160 (0.00%)
         occurrences all number
    0
    3
    0
    Fibromyalgia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Foot deformity
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Groin pain
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Intervertebral disc protrusion
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    2
    1
    0
    Jaw cyst
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Joint range of motion decreased
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Joint swelling
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    0
    0
    2
    Limb discomfort
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Muscle spasms
         subjects affected / exposed
    5 / 161 (3.11%)
    1 / 163 (0.61%)
    4 / 160 (2.50%)
         occurrences all number
    6
    1
    4
    Muscular weakness
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal discomfort
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Musculoskeletal pain
         subjects affected / exposed
    6 / 161 (3.73%)
    3 / 163 (1.84%)
    2 / 160 (1.25%)
         occurrences all number
    8
    4
    2
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    2
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    2 / 160 (1.25%)
         occurrences all number
    0
    1
    2
    Myalgia intercostal
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Neck pain
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    2 / 160 (1.25%)
         occurrences all number
    0
    1
    2
    Osteoarthritis
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    2
    1
    1
    Osteonecrosis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    2
    0
    Osteoporotic fracture
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Pain in extremity
         subjects affected / exposed
    5 / 161 (3.11%)
    2 / 163 (1.23%)
    2 / 160 (1.25%)
         occurrences all number
    6
    2
    2
    Pain in jaw
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    2
    0
    0
    Plantar fasciitis
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Psoriatic arthropathy
         subjects affected / exposed
    8 / 161 (4.97%)
    7 / 163 (4.29%)
    8 / 160 (5.00%)
         occurrences all number
    8
    10
    9
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    0
    0
    2
    Sjogren's syndrome
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Spinal pain
         subjects affected / exposed
    1 / 161 (0.62%)
    5 / 163 (3.07%)
    0 / 160 (0.00%)
         occurrences all number
    1
    8
    0
    Temporomandibular joint syndrome
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    2
    Tenosynovitis
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Hypothyroidism
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    1
    1
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    2
    0
    0
    Dehydration
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 163 (1.23%)
    0 / 160 (0.00%)
         occurrences all number
    0
    2
    0
    Diabetes mellitus
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    1
    0
    2
    Glucose tolerance impaired
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Gout
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    5
    0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 161 (0.00%)
    3 / 163 (1.84%)
    0 / 160 (0.00%)
         occurrences all number
    0
    3
    0
    Hyperglycaemia
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    3
    0
    1
    Hyperlipidaemia
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    2 / 160 (1.25%)
         occurrences all number
    1
    1
    2
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    1
    1
    1
    Hyperuricaemia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    1
    0
    2
    Hypoglycaemia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Malnutrition
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Vitamin B12 deficiency
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Vitamin D deficiency
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    1
    1
    1
    Infections and infestations
    Abscess oral
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Acarodermatitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Bronchitis
         subjects affected / exposed
    8 / 161 (4.97%)
    4 / 163 (2.45%)
    4 / 160 (2.50%)
         occurrences all number
    9
    5
    4
    Candida infection
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    1
    1
    0
    Cellulitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    3
    Chronic tonsillitis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Conjunctivitis
         subjects affected / exposed
    3 / 161 (1.86%)
    2 / 163 (1.23%)
    3 / 160 (1.88%)
         occurrences all number
    3
    2
    3
    Conjunctivitis viral
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Cystitis
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    2
    1
    0
    Ear infection
         subjects affected / exposed
    1 / 161 (0.62%)
    2 / 163 (1.23%)
    0 / 160 (0.00%)
         occurrences all number
    2
    2
    0
    Eye infection bacterial
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Folliculitis
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    0
    0
    4
    Fungal infection
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Gastritis viral
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Gastroenteritis
         subjects affected / exposed
    4 / 161 (2.48%)
    3 / 163 (1.84%)
    1 / 160 (0.63%)
         occurrences all number
    5
    3
    1
    Gastroenteritis viral
         subjects affected / exposed
    2 / 161 (1.24%)
    2 / 163 (1.23%)
    0 / 160 (0.00%)
         occurrences all number
    3
    2
    0
    Gastrointestinal viral infection
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Gingivitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Hand-foot-and-mouth disease
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Helicobacter infection
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Herpes dermatitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Herpes simplex
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Herpes zoster
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    4
    0
    1
    Incision site infection
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Influenza
         subjects affected / exposed
    5 / 161 (3.11%)
    2 / 163 (1.23%)
    2 / 160 (1.25%)
         occurrences all number
    6
    2
    2
    Labyrinthitis
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    2
    0
    0
    Laryngitis
         subjects affected / exposed
    5 / 161 (3.11%)
    2 / 163 (1.23%)
    4 / 160 (2.50%)
         occurrences all number
    5
    2
    4
    Latent tuberculosis
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Localised infection
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    2 / 160 (1.25%)
         occurrences all number
    0
    2
    2
    Lung infection
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Mastitis fungal
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Nail bed infection
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    19 / 161 (11.80%)
    26 / 163 (15.95%)
    15 / 160 (9.38%)
         occurrences all number
    25
    28
    17
    Onychomycosis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Oral bacterial infection
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Oral herpes
         subjects affected / exposed
    1 / 161 (0.62%)
    6 / 163 (3.68%)
    3 / 160 (1.88%)
         occurrences all number
    1
    7
    3
    Otitis externa
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    2
    Otitis media
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Paronychia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Parotitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Pharyngitis
         subjects affected / exposed
    9 / 161 (5.59%)
    5 / 163 (3.07%)
    4 / 160 (2.50%)
         occurrences all number
    10
    5
    5
    Pharyngitis bacterial
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    2
    0
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    2
    1
    0
    Pneumonia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Pulpitis dental
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    1
    1
    0
    Pyuria
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Rash pustular
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    2
    0
    2
    Rhinitis
         subjects affected / exposed
    3 / 161 (1.86%)
    3 / 163 (1.84%)
    2 / 160 (1.25%)
         occurrences all number
    3
    3
    2
    Sinusitis
         subjects affected / exposed
    5 / 161 (3.11%)
    8 / 163 (4.91%)
    2 / 160 (1.25%)
         occurrences all number
    5
    10
    2
    Staphylococcal infection
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Tinea pedis
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    2
    0
    0
    Tinea versicolour
         subjects affected / exposed
    1 / 161 (0.62%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    1
    1
    0
    Tonsillitis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    3
    0
    0
    Tonsillitis bacterial
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Tooth abscess
         subjects affected / exposed
    3 / 161 (1.86%)
    2 / 163 (1.23%)
    2 / 160 (1.25%)
         occurrences all number
    3
    2
    2
    Tooth infection
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 163 (1.23%)
    0 / 160 (0.00%)
         occurrences all number
    0
    2
    0
    Tracheitis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Tuberculosis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    21 / 161 (13.04%)
    16 / 163 (9.82%)
    16 / 160 (10.00%)
         occurrences all number
    25
    17
    17
    Urethritis
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    4 / 161 (2.48%)
    5 / 163 (3.07%)
    8 / 160 (5.00%)
         occurrences all number
    4
    5
    8
    Vaginal infection
         subjects affected / exposed
    3 / 161 (1.86%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    4
    0
    0
    Viral infection
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Viral pharyngitis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Vulvovaginal candidiasis
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Vascular disorders
    Aortic arteriosclerosis
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Arteriosclerosis
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    2
    0
    0
    Blood pressure fluctuation
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Blood pressure inadequately controlled
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Haematoma
         subjects affected / exposed
    1 / 161 (0.62%)
    2 / 163 (1.23%)
    0 / 160 (0.00%)
         occurrences all number
    1
    2
    0
    Hot flush
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Hypertension
         subjects affected / exposed
    5 / 161 (3.11%)
    4 / 163 (2.45%)
    8 / 160 (5.00%)
         occurrences all number
    6
    4
    9
    Lymphoedema
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Peripheral venous disease
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Varicose vein
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Surgical and medical procedures
    Bunion operation
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Mass excision
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Plastic surgery
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Tooth extraction
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    2
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Blepharal papilloma
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Melanocytic naevus
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    0
    0
    2
    Ocular neoplasm
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Thyroid neoplasm
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Immune system disorders
    Allergy to animal
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Drug hypersensitivity
         subjects affected / exposed
    2 / 161 (1.24%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    2
    1
    1
    Food allergy
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Hypersensitivity
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 163 (1.23%)
    3 / 160 (1.88%)
         occurrences all number
    0
    2
    3
    Social circumstances
    Dental prosthesis user
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    General disorders and administration site conditions
    Application site bruise
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Application site pruritus
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Asthenia
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Chest pain
         subjects affected / exposed
    4 / 161 (2.48%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    5
    0
    1
    Cyst
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Drug intolerance
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Enanthema
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Fatigue
         subjects affected / exposed
    6 / 161 (3.73%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    6
    1
    1
    Feeling hot
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Feeling jittery
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Inflammation
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    2 / 160 (1.25%)
         occurrences all number
    0
    1
    2
    Influenza like illness
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 163 (1.23%)
    1 / 160 (0.63%)
         occurrences all number
    0
    2
    1
    Injection site bruising
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    0 / 160 (0.00%)
         occurrences all number
    0
    1
    0
    Injection site erythema
         subjects affected / exposed
    2 / 161 (1.24%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    2
    0
    2
    Injection site pain
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    2 / 160 (1.25%)
         occurrences all number
    2
    0
    2
    Injection site pruritus
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    2
    0
    1
    Injection site reaction
         subjects affected / exposed
    0 / 161 (0.00%)
    1 / 163 (0.61%)
    1 / 160 (0.63%)
         occurrences all number
    0
    1
    1
    Injection site swelling
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Malaise
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    0 / 160 (0.00%)
         occurrences all number
    1
    0
    0
    Mass
         subjects affected / exposed
    1 / 161 (0.62%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    1
    0
    1
    Nodule
         subjects affected / exposed
    0 / 161 (0.00%)
    0 / 163 (0.00%)
    1 / 160 (0.63%)
         occurrences all number
    0
    0
    1
    Oedema
         subjects affected / exposed
    0 / 161 (0.00%)
    2 / 163 (1.23%)
    0 / 160 (0.00%)
         occurrences all number
    0