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    Clinical Trial Results:
    A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate the Efficacy, Safety, and Effect on Radiographic Progression of Brodalumab in Subjects With Psoriatic Arthritis: AMVISION-1

    Summary
    EudraCT number
    		 2013-003554-25
    Trial protocol
    		 GR   CZ   BE   HU   IT   GB   ES   SK   EE   BG   FR  
    Global end of trial date
    22 Oct 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Nov 2016
    First version publication date
    06 Nov 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    20090406
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02029495
    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
    22 Oct 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 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 (140 mg every 2 weeks (Q2W) and 210 mg Q2W) compared to placebo in subjects with active psoriatic arthritis (PsA), as measured by the proportion of subjects achieving an 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 that are consistent with International Conference on Harmonisation (ICH)/Good Clinical Practice (GCP) and applicable regulatory requirements. The final Clinical Study Protocol (CSP), including the final version of the Subject Information and Consent Form(s), was approved in writing by the Independent Ethics Committee (IEC) and Institutional Review Board (IRB) before enrollment of any subject into the study. The Principal Investigator at each center ensured that the subject was given full and adequate oral and written information about the aims, methods, anticipated benefits, and potential hazards of the study. The informed consent form was signed and personally dated by the subject and by the person who conducted the informed consent discussion.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 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
    Poland: 139
    Country: Number of subjects enrolled
    United States: 107
    Country: Number of subjects enrolled
    Russian Federation: 71
    Country: Number of subjects enrolled
    Spain: 21
    Country: Number of subjects enrolled
    Czech Republic: 19
    Country: Number of subjects enrolled
    Hungary: 15
    Country: Number of subjects enrolled
    Slovakia: 15
    Country: Number of subjects enrolled
    United Kingdom: 15
    Country: Number of subjects enrolled
    Mexico: 12
    Country: Number of subjects enrolled
    Switzerland: 12
    Country: Number of subjects enrolled
    Bulgaria: 9
    Country: Number of subjects enrolled
    Canada: 9
    Country: Number of subjects enrolled
    Estonia: 9
    Country: Number of subjects enrolled
    Italy: 9
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Greece: 6
    Country: Number of subjects enrolled
    Belgium: 2
    Worldwide total number of subjects
    478
    EEA total number of subjects
    267
    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)
    427
    From 65 to 84 years
    51
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects were recruited at 121 clinical sites in 17 countries worldwide. The first subject enrolled on 06 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 biologic use, and geographic region (North America, Central and Eastern Europe, Western Europe, and Latin America).

    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.

    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
    158
    159
    Received Treatment
    159
    158
    158
    Ongoing Study at Week 16
    95
    101
    108
    Ongoing Study at Week 24
    68
    76
    84
    Ongoing Study at Week 52
    10
    12
    14
    Completed
    0
    0
    0
    Not completed
    161
    158
    159
         Consent withdrawn by subject
    31
    29
    15
         Lost to follow-up
    1
    1
    -
         Decision by sponsor
    129
    128
    144

    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
    		 161 158 159 478
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    		 145 138 144 427
        From 65-84 years
    		 16 20 15 51
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 48.1 ± 11.79 49.9 ± 12.8 49.1 ± 12.24 -
    Gender Categorical
    Units: Subjects
        Female
    		 80 80 70 230
        Male
    		 81 78 89 248
    Race
    Units: Subjects
        White
    		 152 152 155 459
        Asian
    		 4 0 0 4
        American Indian or Alaska Native
    		 0 0 2 2
        Other
    		 5 6 2 13
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 11 9 19 39
        Not Hispanic or Latino
    		 150 149 140 439
    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, 158, 159 subjects in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 6.4 ± 7.96 8.2 ± 8.63 7.7 ± 9.2 -
    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, 151, and 149 participants in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 11.9 ± 7.27 13.5 ± 8.2 13.7 ± 7.43 -
    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, 157, 156 participants in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 8 ± 7.03 9.5 ± 7.85 8.1 ± 6.89 -
    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, 157, and 156 subjects in each group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 5.6 ± 1.88 5.5 ± 2.04 5.4 ± 2.05 -
    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). Data are available for 160, 158, 159 participants in each treatment group respectively.
    Units: entheses
        arithmetic mean (standard deviation)
    		 1.9 ± 1.94 1.8 ± 2 1.6 ± 1.87 -
    Dactylitis Score
    The dactylitis count is defined as the sum of 20 fingers/toes that exhibit dactylitis (absent 0, present 1). Data are available for 160, 158, 159 participants in each treatment group respectively.
    Units: digits
        arithmetic mean (standard deviation)
    		 2.3 ± 3.55 2.6 ± 4.23 2.2 ± 3.86 -
    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). Data are available for 159, 157, 156 participants in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 1.2 ± 0.59 1.3 ± 0.65 1.2 ± 0.57 -
    Swollen Joint Count
    Data available for 160, 158, and 159 subjects in each treatment group respectively.
    Units: joints
        arithmetic mean (standard deviation)
    		 12.3 ± 8.33 13.3 ± 10.1 12.4 ± 10.2 -
    Tender Joint Count
    Data available for 160, 158, and 159 subjects in each treatment group respectively.
    Units: joints
        arithmetic mean (standard deviation)
    		 21.4 ± 14.8 23.4 ± 15.5 20.7 ± 14.4 -
    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 158, 157, and 155 subjects in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 5 ± 1.1 5.2 ± 1.2 4.9 ± 1.1 -
    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, 157, 155 subjects in each treatment group respectively
    Units: mm
        arithmetic mean (standard deviation)
    		 58.5 ± 18 60.3 ± 21.2 58.5 ± 19.3 -
    Patient Global Assessment of Disease Activity
    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, 157, 156 subjects in each treatment group respectively.
    Units: mm
        arithmetic mean (standard deviation)
    		 58.9 ± 23.3 59.9 ± 23.1 58.6 ± 22.9 -
    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, 157, 156 subjects in each treatment group respectively.
    Units: mm
        arithmetic mean (standard deviation)
    		 53.7 ± 23.5 54.8 ± 23.5 52.5 ± 24.9 -
    C-Reactive Protein (CRP)
    Data available for 161, 158, 158 subjects in each treatment group respectively.
    Units: mg/L
        arithmetic mean (standard deviation)
    		 15.3 ± 21.83 19.4 ± 29.92 17.1 ± 26.59 -
    Erythrocyte Sedimentation Rate (ESR)
    Data available for 157, 155, 157 subjects in each treatment group respectively.
    Units: mm/hr
        arithmetic mean (standard deviation)
    		 35.2 ± 25.55 35.8 ± 22.9 38.8 ± 31.85 -
    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 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 156, 157, and 155 subjects in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 29.1 ± 13.57 31.6 ± 14.17 28.7 ± 13.46 -
    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, rolephysical, 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, 157, and 156 participants in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 33.3 ± 8.59 32.6 ± 9.45 34.6 ± 9.06 -
    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, 157, 156 participants in each treatment group respectively.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 53.2 ± 10.23 52.7 ± 10.35 53.2 ± 10.53 -

    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
    122
    118
    121
    Units: percentage of participants
        number (not applicable)
    13.9
    39.8
    51.2
    Statistical analysis title
    		 Primary Analysis
    Comparison groups
    Placebo v Brodalumab 140 mg
    Number of subjects included in analysis
    240
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference from placebo
    Point estimate
    25.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 15.1
         upper limit
    		 36.7
    Notes
    [1] - Cochran-Mantel-Haenszel approach stratified by baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes/no) and geographic region (North and Latin American, Central/Eastern Europe, Western Europe).
    Statistical analysis title
    		 Primary Analysis
    Comparison groups
    Placebo v Brodalumab 210 mg
    Number of subjects included in analysis
    243
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference from placebo
    Point estimate
    37.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 26.5
         upper limit
    		 48.1
    Notes
    [2] - Cochran-Mantel-Haenszel approach stratified by baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes/no) and geographic region (North and Latin American, Central/Eastern Europe, Western Europe).

    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
    78
    90
    77
    Units: percentage of participants
        number (not applicable)
    10.3
    48.9
    75.3
    Statistical analysis title
    		 Difference in Response Rate
    Comparison groups
    Placebo v Brodalumab 210 mg
    Number of subjects included in analysis
    155
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference from placebo
    Point estimate
    65.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 53.3
         upper limit
    		 76.8
    Notes
    [3] - Cochran-Mantel-Haenszel test stratified by baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes/no), baseline PASI score (≤ median, > median) and region (North and Latin America, Central and Eastern Europe, Western Europe/Australia).
    Statistical analysis title
    		 Difference in Response Rates
    Comparison groups
    Placebo v Brodalumab 140 mg
    Number of subjects included in analysis
    168
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference from placebo
    Point estimate
    38.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 26.3
         upper limit
    		 51
    Notes
    [4] - Cochran-Mantel-Haenszel test stratified by baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes/no), baseline PASI score (≤ median, > median) and region (North and Latin America, Central and 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
    93
    98
    106
    Units: units on a scale
        least squares mean (standard error)
    -0.101 ± 0.0484
    -0.339 ± 0.0478
    -0.469 ± 0.0468
    Statistical analysis title
    		 Comparison with Placebo
    Comparison groups
    Placebo v Brodalumab 140 mg
    Number of subjects included in analysis
    191
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0002 [5]
    Method
    		 Mixed effects model repeated measures
    Parameter type
    		 LS mean difference
    Point estimate
    -0.237
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.362
         upper limit
    		 -0.112
    Notes
    [5] - The model contains visit, treatment, treatment-by-visit and baseline-by-visit interaction, baseline, and three randomization strata (baseline weight, prior biologic use, and geographic region).
    Statistical analysis title
    		 Comparison with Placebo
    Comparison groups
    Placebo v Brodalumab 210 mg
    Number of subjects included in analysis
    199
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [6]
    Method
    		 Mixed effects model repeated measures
    Parameter type
    		 Least squares (LS) mean difference
    Point estimate
    -0.368
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.491
         upper limit
    		 -0.244
    Notes
    [6] - The model contains visit, treatment, treatment-by-visit and baseline-by-visit interaction, baseline, and three randomization strata (baseline weight, 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
    72
    88
    73
    Units: percentage of participants
        number (not applicable)
    8.3
    45.5
    49.3
    Statistical analysis title
    		 Difference in Response Rate
    Comparison groups
    Placebo v Brodalumab 210 mg
    Number of subjects included in analysis
    145
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [7]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference from placebo
    Point estimate
    41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 27.9
         upper limit
    		 54.1
    Notes
    [7] - Cochran-Mantel-Haenszel approach stratified by baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes/no), and geographic region (North and Latin American, Central/Eastern Europe, Western Europe)
    Statistical analysis title
    		 Difference in Response Rate
    Comparison groups
    Placebo v Brodalumab 140 mg
    Number of subjects included in analysis
    160
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [8]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference from placebo
    Point estimate
    37.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 24.9
         upper limit
    		 49.3
    Notes
    [8] - Cochran-Mantel-Haenszel approach stratified by baseline weight (≤ 100 kg, > 100 kg), prior biologic use (yes/no), and geographic region (North and Latin American, Central/Eastern Europe, Western Europe).

    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 in the primary analysis.
    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
    122
    118
    121
    Units: percentage of participants
    number (not applicable)
        Week 2
    9
    18.6
    23.1
        Week 4
    11.5
    23.7
    39.7
        Week 8
    16.4
    41.5
    52.9
        Week 12
    18.9
    40.7
    52.9
    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
    112
    115
    113
    Units: units on a scale
    least squares mean (standard error)
        Week 2 (N = 112, 115, 113)
    -0.043 ± 0.0362
    -0.123 ± 0.0364
    -0.227 ± 0.0364
        Week 4 (N = 109, 114, 112)
    -0.081 ± 0.0409
    -0.197 ± 0.0407
    -0.354 ± 0.0407
        Week 8 (N = 102, 111, 114)
    -0.101 ± 0.0451
    -0.279 ± 0.0442
    -0.387 ± 0.0439
        Week 12 (N = 100, 108, 112)
    -0.125 ± 0.0496
    -0.31 ± 0.0486
    -0.412 ± 0.0481
    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; 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
    78
    90
    77
    Units: percentage of participants
    number (not applicable)
        Week 2
    2.6
    14.4
    20.8
        Week 4
    6.4
    35.6
    54.5
        Week 8
    9
    47.8
    71.4
        Week 12
    9
    51.1
    83.1
    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 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15
    End point values
    		 Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    72
    88
    73
    Units: percentage of participants
    number (not applicable)
        Week 1
    9.7
    9.1
    11
        Week 2
    9.7
    21.6
    20.5
        Week 3
    6.9
    28.4
    38.4
        Week 4
    6.9
    38.6
    47.9
        Week 5
    5.6
    37.5
    47.9
        Week 6
    4.2
    45.5
    46.6
        Week 7
    8.3
    43.2
    57.5
        Week 8
    9.7
    43.2
    54.8
        Week 9
    6.9
    43.2
    53.4
        Week 10
    5.6
    43.2
    49.3
        Week 11
    9.7
    46.6
    53.4
        Week 12
    8.3
    43.2
    50.7
        Week 13
    5.6
    43.2
    54.8
        Week 14
    9.7
    43.2
    50.7
        Week 15
    6.9
    48.9
    49.3
    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: o Patient's assessment of joint pain (measured on a 100 mm VAS); o Patient's Global Assessment (measured on a 100 mm VAS); o Physician Global Assessment of disease activity (measured on a 100 mm VAS); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o 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
    122
    118
    121
    Units: percentage of participants
    number (not applicable)
        Week 2
    0.8
    4.2
    4.1
        Week 4
    2.5
    11
    11.6
        Week 8
    4.9
    16.9
    25.6
        Week 12
    4.9
    17.8
    29.8
        Week 16
    4.1
    20.3
    29.8
    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: o Patient's assessment of joint pain (measured on a 100 mm VAS); o Patient's Global Assessment (measured on a 100 mm VAS); o Physician Global Assessment of disease activity (measured on a 100 mm VAS); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o 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
    122
    118
    121
    Units: percentage of participants
    number (not applicable)
        Week 2
    0
    0
    1.7
        Week 4
    0
    2.5
    4.1
        Week 8
    1.6
    6.8
    10.7
        Week 12
    2.5
    9.3
    12.4
        Week 16
    2.5
    10.2
    14.9
    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, 14, and 16
    End point values
    		 Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    122
    118
    121
    Units: joints
    least squares mean (standard error)
        Week 2 (N = 115, 115, 117)
    -2.471 ± 0.8609
    -4.209 ± 0.8738
    -5.857 ± 0.8566
        Week 4 (N = 111, 114, 117)
    -2.752 ± 0.932
    -5.594 ± 0.935
    -6.99 ± 0.9129
        Week 8 (N = 103, 109, 117)
    -3.417 ± 1.0241
    -8.46 ± 1.0162
    -9.183 ± 0.9814
        Week 12 (N = 100, 107, 116)
    -2.205 ± 1.1855
    -8.512 ± 1.1732
    -9.493 ± 1.1315
        Week 14 (N = 99, 105, 113)
    -1.515 ± 1.2202
    -9.879 ± 1.2059
    -9.999 ± 1.1626
        Week 16 (N = 93, 98, 110)
    0.591 ± 1.2844
    -10.82 ± 1.264
    -8.765 ± 1.2115
    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 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, 14, and 16
    End point values
    		 Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    122
    118
    121
    Units: joints
    least squares mean (standard error)
        Week 2 (N = 115, 115, 117)
    -2.7 ± 0.6737
    -3.238 ± 0.6737
    -2.893 ± 0.6691
        Week 4 (N = 111, 114, 117)
    -2.316 ± 0.6391
    -3.737 ± 0.6368
    -4.325 ± 0.6252
        Week 8 (N = 103, 109, 117)
    -2.451 ± 0.731
    -5.548 ± 0.7205
    -5.95 ± 0.6989
        Week 12 (N = 100, 107, 116)
    -2.44 ± 0.7858
    -5.949 ± 0.7724
    -6.467 ± 0.7469
        Week 14 (N = 99, 105, 113)
    -1.662 ± 0.793
    -6.574 ± 0.779
    -6.661 ± 0.7531
        Week 16 (N = 93, 98, 110)
    -0.216 ± 0.8879
    -6.912 ± 0.8698
    -5.829 ± 0.8343
    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
    122
    118
    121
    Units: mm
    least squares mean (standard error)
        Week 2 (N = 112, 115, 113)
    3.984 ± 1.9556
    0.254 ± 1.9584
    -4.852 ± 1.9619
        Week 4 (N = 109, 114, 112)
    4.672 ± 2.1652
    -3.359 ± 2.1429
    -9.03 ± 2.1462
        Week 8 (N = 102, 111, 114)
    2.685 ± 2.3086
    -7.256 ± 2.2534
    -12.98 ± 2.236
        Week 12 (N = 100, 108, 112)
    3.123 ± 2.4577
    -6.31 ± 2.402
    -14.36 ± 2.3714
        Week 16 (N = 93, 98, 106)
    3.919 ± 2.4394
    -7.635 ± 2.3942
    -16.5 ± 2.3507
    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
    122
    118
    121
    Units: mm
    least squares mean (standard error)
        Week 2 (N = 112, 115, 113)
    0.375 ± 1.877
    -3.247 ± 1.8953
    -7.492 ± 1.8882
        Week 4 (N = 109, 114, 112)
    2.375 ± 2.0807
    -5.291 ± 2.0747
    -13.41 ± 2.0677
        Week 8 (N = 102, 111, 114)
    0.524 ± 2.1619
    -8.264 ± 2.1278
    -16.89 ± 2.1036
        Week 12 (N = 100, 108, 112)
    0.015 ± 2.3726
    -7.668 ± 2.3296
    -18.22 ± 2.2912
        Week 16 (N = 93, 98, 106)
    2.16 ± 2.4211
    -10.62 ± 2.3911
    -19.95 ± 1.3332
    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
    122
    118
    121
    Units: mm
    least squares mean (standard error)
        Week 2 (N = 110, 115, 112)
    -5.576 ± 1.8452
    -11.4 ± 1.8303
    -16.73 ± 1.8436
        Week 4 (N = 104, 113, 110)
    -10.35 ± 2.0579
    -16.56 ± 2.0072
    -22.22 ± 2.0203
        Week 8 (N = 98, 111, 112)
    -9.832 ± 2.199
    -21.14 ± 2.1124
    -27.4 ± 2.103
        Week 12 (N = 96, 107, 112)
    -9.305 ± 2.2447
    -24.24 ± 2.1652
    -28.44 ± 2.1354
        Week 16 (N = 92, 98, 105)
    -8.125 ± 2.3987
    -27.39 ± 2.3369
    -29.22 ± 2.2903
    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
    122
    118
    121
    Units: mg/L
    arithmetic mean (standard deviation)
        Week 2 (N = 114, 117, 115)
    1.75 ± 13.315
    -4.81 ± 25.738
    -5.9 ± 20.412
        Week 4 (N = 112, 116, 116)
    -1.05 ± 12.231
    -6.05 ± 24.632
    -7.21 ± 18.933
        Week 8 (N = 103, 111, 117)
    -0.5 ± 14.042
    -6.27 ± 27.959
    -6.11 ± 17.657
        Week 12 (N = 102, 109, 115)
    -1.31 ± 14.526
    -5.56 ± 29.137
    -5.95 ± 15.335
        Week 16 (N = 94, 98, 108)
    -1.37 ± 17.314
    -6.94 ± 29.973
    -6.41 ± 12.685
    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
    122
    118
    121
    Units: mm/hr
    arithmetic mean (standard deviation)
        Week 2 (N = 109, 113, 115)
    1.8 ± 14.62
    -3.9 ± 16.95
    -7.6 ± 19.25
        Week 4 (N = 109, 112, 115)
    -0.3 ± 16.63
    -6 ± 20.81
    -7.8 ± 21.9
        Week 8 (N = 102, 107, 115)
    -0.9 ± 15.44
    -6.6 ± 19.83
    -11.1 ± 21.69
        Week 12 (N = 96, 107, 115)
    0.4 ± 20.35
    -8.9 ± 20.38
    -10.8 ± 23.74
        Week 16 (N = 92, 94, 107)
    -2.4 ± 18.43
    -7.5 ± 21.91
    -11.4 ± 21.54
    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
    122
    118
    121
    Units: units on a scale
    least squares mean (standard error)
        Week 2 (N = 109, 111, 111)
    -0.212 ± 0.085
    -0.442 ± 0.0866
    -0.794 ± 0.0853
        Week 4 (N = 108, 112, 111)
    -0.279 ± 0.0937
    -0.694 ± 0.0942
    -1.075 ± 0.093
        Week 8 (N = 100, 107, 114)
    -0.418 ± 0.1108
    -0.99 ± 0.1099
    -1.246 ± 0.1071
        Week 12 (N = 96, 107, 111)
    -0.296 ± 0.1184
    -1.021 ± 0.1161
    -1.323 ± 0.1133
        Week 16 (N = 93, 98, 104)
    -0.152 ± 0.1282
    -1.201 ± 0.1264
    -1.405 ± 0.1229
    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
    122
    118
    121
    Units: digits
    least squares mean (standard error)
        Week 4 (N = 55, 59, 61)
    -0.713 ± 0.3861
    -1.164 ± 0.3862
    -1.526 ± 0.368
        Week 12 (N = 52, 55, 62)
    -1.012 ± 0.4639
    -2.688 ± 0.463
    -3.058 ± 0.4307
        Week 16 (N = 45, 50, 57)
    -0.47 ± 0.5358
    -2.981 ± 0.522
    -2.851 ± 0.4883
    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 postbaseline 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
    122
    118
    121
    Units: entheses
    least squares mean (standard error)
        Week 4 (N = 78, 72, 60)
    -0.496 ± 0.1863
    -0.805 ± 0.193
    -0.92 ± 0.2042
        Week 12 (N = 70, 68, 61)
    -0.485 ± 0.2084
    -1.209 ± 0.2123
    -1.399 ± 0.2194
        Week 16 (N = 63, 60, 56)
    -0.403 ± 0.2192
    -1.099 ± 0.2243
    -1.318 ± 0.2316
    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
    122
    118
    121
    Units: units on a scale
    least squares mean (standard error)
        Week 12 (N = 100, 108, 112)
    -0.219 ± 0.2051
    -0.86 ± 0.2019
    -1.468 ± 0.1968
        Week 16 (N = 92, 98, 106)
    -0.117 ± 0.2066
    -1.049 ± 0.2038
    -1.777 ± 0.1979
    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
    122
    118
    121
    Units: units on a scale
    least squares mean (standard error)
        Week 2 (N = 108, 112, 112)
    -3.312 ± 0.9322
    -4.767 ± 0.9328
    -7.698 ± 0.9266
        Week 4 (N = 103, 111, 109)
    -3.54 ± 0.9621
    -7.03 ± 0.9464
    -10.23 ± 0.9423
        Week 8 (N = 97, 108, 112)
    -4.56 ± 1.1225
    -10.64 ± 1.094
    -11.94 ± 1.0747
        Week 12 (N = 93, 106, 111)
    -4.127 ± 1.2229
    -10.74 ± 1.1828
    -13.21 ± 1.1578
        Week 16 (N = 92, 98, 105)
    -1.319 ± 1.2992
    -13.1 ± 1.265
    -13.26 ± 1.232
    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
    122
    118
    121
    Units: percentage of participants
    number (not applicable)
        Week 2
    18
    33.1
    38.8
        Week 4
    23.8
    39.8
    50.4
        Week 8
    23
    51.7
    58.7
        Week 12
    24.6
    53.4
    65.3
        Week 16
    19.7
    51.7
    62.8
    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
    122
    118
    121
    Units: units on a scale
    least squares mean (standard error)
        Week 12 (N = 92, 105, 110)
    5.963 ± 0.1567
    4.864 ± 0.1501
    4.276 ± 0.1467
        Week 16 (N = 91, 98, 102)
    6.133 ± 0.1676
    4.675 ± 0.1622
    4.104 ± 0.1594
    No statistical analyses for this end point

    Secondary: Change from Baseline in Van der Heijde modified Total Sharp Score (mTSS) at Week 24

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    End point title
    		 Change from Baseline in Van der Heijde modified Total Sharp Score (mTSS) at Week 24
    End point description
    The modified Total Sharp Score (mTSS) is a measure of change in joint health using radiography of the hands and feet. Bony erosions of the joints and the narrowing of the space between the joints are quantified by the erosion (ES) and joint space narrowing (JSN) scores. Erosions of the hands were scored on a scale from 0 to 5, and erosions of the feet were scored from 0 to 10. JSN was scored on a scale from 0 to 4. The total mTSS score is a sum of the erosion and joint scores and ranges from 0 (normal) to 528 (worst). The full analysis set (all randomized participants) was used for this analysis; subjects with baseline and post-baseline results are included.
    End point type
    Secondary
    End point timeframe
    Baseline and week 24
    End point values
    		 Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    82
    97
    104
    Units: units on a scale
        arithmetic mean (standard deviation)
    0.823 ± 2.9911
    0.342 ± 1.2843
    0.356 ± 2.4669
    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
    78
    90
    77
    Units: percentage of participants
    number (not applicable)
        Week 2
    1.3
    5.6
    6.5
        Week 4
    2.6
    18.9
    28.6
        Week 8
    2.6
    24.4
    53.2
        Week 12
    5.1
    37.8
    61
        Week 16
    7.7
    40
    64.9
    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
    78
    90
    77
    Units: percentage of participants
    number (not applicable)
        Week 2
    1.3
    2.2
    3.9
        Week 4
    2.6
    11.1
    13
        Week 8
    2.6
    15.6
    32.5
        Week 12
    2.6
    18.9
    42.9
        Week 16
    3.8
    20
    48.1
    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
    78
    90
    77
    Units: percent change
    arithmetic mean (standard deviation)
        Week 2 (N = 74, 90, 73)
    -9.37 ± 29.614
    -37.57 ± 31.835
    -48.21 ± 29.79
        Week 4 (N = 70, 88, 73)
    -10.59 ± 65.285
    -52.06 ± 39.626
    -63.47 ± 60.345
        Week 8 (N = 68, 86, 76)
    -11.95 ± 53.453
    -57.06 ± 53.538
    -74.14 ± 77.71
        Week 12 (N = 68, 85, 75)
    -2.93 ± 64.279
    -60.8 ± 44.703
    -86.69 ± 23.551
        Week 16 (N = 63, 77, 69)
    -0.26 ± 79.793
    -65.03 ± 43.748
    -87.44 ± 23.857
    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
    78
    90
    77
    Units: percent involvement
    least squares mean (standard error)
        Week 2 (N = 74, 90, 73)
    15.642 ± 0.9755
    12.967 ± 0.9081
    13.076 ± 0.9803
        Week 4 (N = 70, 88, 73)
    15.432 ± 1.1574
    10.658 ± 1.0596
    7.819 ± 1.1391
        Week 8 (N = 68, 86, 76)
    14.928 ± 1.251
    9.693 ± 1.1375
    5.712 ± 1.2159
        Week 12 (N = 68, 85, 75)
    14.938 ± 1.2732
    8.766 ± 1.159
    3.153 ± 1.2356
        Week 16 (N = 63, 77, 69)
    15.923 ± 1.4281
    7.285 ± 1.2991
    2.308 ± 1.3841
    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
    122
    118
    121
    Units: units on a scale
    least squares mean (standard error)
        Week 2 (N = 112, 115, 113)
    -1.335 ± 0.4176
    -2.655 ± 0.4191
    -3.661 ± 0.4194
        Week 4 (N = 109, 114, 112)
    -1.71 ± 0.4275
    -4.211 ± 0.425
    -4.967 ± 0.4245
        Week 8 (N = 102, 111, 114)
    -1.834 ± 0.456
    -4.54 ± 0.4486
    -5.499 ± 0.4453
        Week 12 (N = 100, 108, 112)
    -1.7 ± 0.4788
    -4.677 ± 0.4716
    -6.17 ± 0.4668
        Week 16 (N = 93, 98, 106)
    -1.543 ± 0.5011
    -4.498 ± 0.4945
    -6.131 ± 0.4862
    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
    122
    118
    121
    Units: units on a scale
    least squares mean (standard error)
        Physical Component: Week 12 (N = 100, 108, 112)
    1.612 ± 0.8791
    3.806 ± 0.8706
    6.143 ± 0.8412
        Physical Component: Week 16 (N = 92, 98, 106)
    0.481 ± 0.9084
    4.715 ± 0.9019
    7.503 ± 0.8679
        Mental Component: Week 12 (N = 100, 108, 112)
    2.09 ± 0.8115
    4.812 ± 0.7977
    3.424 ± 0.7782
        Mental Component: Week 16 (N = 92, 98, 106)
    2.542 ± 0.8214
    4.4 ± 0.8098
    3.821 ± 0.7863
    No statistical analyses for this end point

    Secondary: Plasma Concentration of Brodalumab

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    End point title
    		 Plasma Concentration of Brodalumab
    End point description
    Plasma concentrations are calculated using log-transformed data from subjects with measurable levels > lower limit of quantitation (LLOQ) of 50 ng/mL. The Pharmacokinetic (PK) analysis set included all subjects in the safety subset who had at least 1 evaluable PK concentration measurement.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 8, 12, and 16
    End point values
    		 Placebo Brodalumab 140 mg Brodalumab 210 mg
    Number of subjects analysed
    0 [9]
    155
    154
    Units: ng/mL
    geometric mean (standard deviation)
        Week 1 (N = 129, 141)
    ±
    2017 ± 3712.5
    5528 ± 5546.4
        Week 2 (N = 138, 140)
    ±
    4807 ± 6051.7
    11870 ± 9902.7
        Week 4 (N = 106, 136)
    ±
    2341 ± 5151.7
    8912 ± 10920
        Week 8 (N = 51, 112)
    ±
    2100 ± 4124
    7029 ± 11579
        Week 12 (N = 50, 107)
    ±
    1233 ± 3089.5
    4830 ± 12370
        Week 16 (N = 33, 84)
    ±
    1929 ± 2511.6
    5276 ± 10970
    Notes
    [9] - 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 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.

    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.

    Serious adverse events
    		 Placebo Brodalumab 140 mg Q2W Brodalumab 210 mg Q2W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    12 / 159 (7.55%)
    7 / 158 (4.43%)
    11 / 158 (6.96%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant melanoma
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Squamous cell carcinoma of the vulva
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Uterine leiomyoma
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Vulval cancer stage 0
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Vascular disorders
    Vasculitis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Surgical and medical procedures
    Arthrodesis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    General disorders and administration site conditions
    Impaired healing
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Reproductive system and breast disorders
    Hydrometra
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea exertional
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Nasal septum deviation
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Haemoglobin decreased
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Arthropod bite
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Eye injury
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Injury
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Iris injury
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Keratorhexis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Spinal fracture
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (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
    Tendon rupture
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Acute myocardial infarction
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Atrial fibrillation
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (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
    Transient ischaemic attack
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (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
    Eye disorders
    Lens dislocation
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (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
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Drug reaction with eosinophilia and systemic symptoms
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (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
    Skin necrosis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chondropathy
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Muscular weakness
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (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
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Synovial disorder
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Infections and infestations
    Erysipelas
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Infected fistula
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (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
    Infectious mononucleosis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (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
    Urosepsis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (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
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo Brodalumab 140 mg Q2W Brodalumab 210 mg Q2W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    95 / 159 (59.75%)
    102 / 158 (64.56%)
    98 / 158 (62.03%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    3
    0
    Angiomyolipoma
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Enchondroma
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Melanocytic naevus
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    1
    Seborrhoeic keratosis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Vascular disorders
    Diastolic hypertension
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Haematoma
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Hot flush
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Hypertension
         subjects affected / exposed
    6 / 159 (3.77%)
    2 / 158 (1.27%)
    7 / 158 (4.43%)
         occurrences all number
    6
    2
    10
    Hypotension
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Peripheral venous disease
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Surgical and medical procedures
    Acrochordon excision
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Bunion operation
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Bone lesion excision
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Tooth extraction
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Wound closure
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    General disorders and administration site conditions
    Application site pruritus
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Asthenia
         subjects affected / exposed
    0 / 159 (0.00%)
    3 / 158 (1.90%)
    0 / 158 (0.00%)
         occurrences all number
    0
    3
    0
    Chest discomfort
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    2
    0
    Chills
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Drug intolerance
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Face oedema
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Fatigue
         subjects affected / exposed
    2 / 159 (1.26%)
    2 / 158 (1.27%)
    1 / 158 (0.63%)
         occurrences all number
    2
    2
    1
    Foreign body reaction
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Inflammation
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Injection site erythema
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    7
    1
    2
    Injection site haematoma
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    1
    2
    0
    Injection site pain
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Injection site pruritus
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Injection site reaction
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    2 / 158 (1.27%)
         occurrences all number
    0
    0
    2
    Local swelling
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Malaise
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Nodule
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Medical device complication
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Oedema
         subjects affected / exposed
    2 / 159 (1.26%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    2
    0
    0
    Oedema peripheral
         subjects affected / exposed
    2 / 159 (1.26%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    2
    0
    1
    Peripheral swelling
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Pyrexia
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Immune system disorders
    Allergy to arthropod bite
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Drug hypersensitivity
         subjects affected / exposed
    2 / 159 (1.26%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    2
    0
    0
    Hypersensitivity
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Multiple allergies
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    2
    Seasonal allergy
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Reproductive system and breast disorders
    Amenorrhoea
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    2
    0
    Breast pain
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Hydrometra
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Ovarian cyst
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    1
    Prostatitis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Allergic sinusitis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Asthma
         subjects affected / exposed
    3 / 159 (1.89%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    3
    1
    0
    Catarrh
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Cough
         subjects affected / exposed
    4 / 159 (2.52%)
    2 / 158 (1.27%)
    2 / 158 (1.27%)
         occurrences all number
    5
    2
    2
    Dyspnoea
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Epistaxis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    3 / 159 (1.89%)
    1 / 158 (0.63%)
    2 / 158 (1.27%)
         occurrences all number
    3
    1
    2
    Nasal congestion
         subjects affected / exposed
    3 / 159 (1.89%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    3
    0
    0
    Respiratory disorder
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Respiratory tract congestion
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    0 / 158 (0.00%)
         occurrences all number
    0
    2
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Upper respiratory tract inflammation
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Psychiatric disorders
    Adjustment disorder
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Agitation
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Anger
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Anxiety
         subjects affected / exposed
    2 / 159 (1.26%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    2
    1
    0
    Bruxism
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Depressed mood
         subjects affected / exposed
    0 / 159 (0.00%)
    3 / 158 (1.90%)
    0 / 158 (0.00%)
         occurrences all number
    0
    3
    0
    Depression
         subjects affected / exposed
    1 / 159 (0.63%)
    2 / 158 (1.27%)
    0 / 158 (0.00%)
         occurrences all number
    1
    2
    0
    Emotional disorder
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Insomnia
         subjects affected / exposed
    1 / 159 (0.63%)
    3 / 158 (1.90%)
    1 / 158 (0.63%)
         occurrences all number
    1
    3
    1
    Nightmare
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Sleep disorder
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    0 / 158 (0.00%)
         occurrences all number
    0
    2
    0
    Investigations
    Alanine aminotransferase abnormal
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 159 (1.89%)
    2 / 158 (1.27%)
    2 / 158 (1.27%)
         occurrences all number
    3
    2
    3
    Aspartate aminotransferase abnormal
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 159 (1.26%)
    0 / 158 (0.00%)
    3 / 158 (1.90%)
         occurrences all number
    2
    0
    3
    Blood cholesterol increased
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Blood glucose increased
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Haematology test abnormal
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Blood pressure increased
         subjects affected / exposed
    3 / 159 (1.89%)
    0 / 158 (0.00%)
    2 / 158 (1.27%)
         occurrences all number
    3
    0
    2
    Haemoglobin decreased
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    2
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    High density lipoprotein decreased
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Liver function test abnormal
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Low density lipoprotein increased
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Neutrophil count increased
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Platelet count decreased
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Platelet count increased
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Streptococcus test positive
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Transaminases increased
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Vitamin D decreased
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    1
    1
    0
    Weight decreased
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Weight increased
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    5 / 158 (3.16%)
         occurrences all number
    0
    1
    5
    White blood cell count increased
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Arthropod bite
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Contusion
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    2
    1
    0
    Burns second degree
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Fall
         subjects affected / exposed
    4 / 159 (2.52%)
    2 / 158 (1.27%)
    1 / 158 (0.63%)
         occurrences all number
    4
    2
    1
    Hand fracture
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Humerus fracture
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Joint injury
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Laceration
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    1
    Ligament rupture
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Limb crushing injury
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Ligament sprain
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    2 / 158 (1.27%)
         occurrences all number
    1
    1
    2
    Limb injury
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Muscle strain
         subjects affected / exposed
    1 / 159 (0.63%)
    2 / 158 (1.27%)
    0 / 158 (0.00%)
         occurrences all number
    1
    2
    0
    Meniscus injury
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    0 / 158 (0.00%)
         occurrences all number
    0
    2
    0
    Radius fracture
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Skin abrasion
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Synovial rupture
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Tendon rupture
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Upper limb fracture
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Wound
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Coronary artery disease
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Palpitations
         subjects affected / exposed
    2 / 159 (1.26%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    2
    0
    0
    Tachycardia
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Nervous system disorders
    Carotid artery stenosis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Ageusia
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Cluster headache
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 159 (0.63%)
    3 / 158 (1.90%)
    1 / 158 (0.63%)
         occurrences all number
    1
    3
    1
    Headache
         subjects affected / exposed
    4 / 159 (2.52%)
    4 / 158 (2.53%)
    5 / 158 (3.16%)
         occurrences all number
    5
    4
    5
    Hemianopia
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Hypoaesthesia
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Lethargy
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Paraesthesia
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Migraine
         subjects affected / exposed
    2 / 159 (1.26%)
    2 / 158 (1.27%)
    0 / 158 (0.00%)
         occurrences all number
    2
    2
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Restless legs syndrome
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    1
    2
    0
    Resting tremor
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Sciatica
         subjects affected / exposed
    3 / 159 (1.89%)
    2 / 158 (1.27%)
    2 / 158 (1.27%)
         occurrences all number
    3
    3
    3
    Sinus headache
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    2
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 159 (0.63%)
    3 / 158 (1.90%)
    2 / 158 (1.27%)
         occurrences all number
    1
    4
    2
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    2 / 158 (1.27%)
         occurrences all number
    0
    0
    2
    Leukopenia
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    1
    Lymphadenitis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Lymphadenopathy
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Microcytic anaemia
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Neutropenia
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Tinnitus
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Vertigo
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    1
    1
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Diplopia
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Eye pain
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Iridocyclitis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Photophobia
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Uveitis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Vision blurred
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 159 (0.00%)
    3 / 158 (1.90%)
    0 / 158 (0.00%)
         occurrences all number
    0
    3
    0
    Abdominal pain lower
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    3 / 158 (1.90%)
         occurrences all number
    0
    1
    3
    Abdominal tenderness
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Aphthous ulcer
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Apical granuloma
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Constipation
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Dental caries
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Dental necrosis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Dental cyst
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Dry mouth
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Diarrhoea
         subjects affected / exposed
    6 / 159 (3.77%)
    5 / 158 (3.16%)
    2 / 158 (1.27%)
         occurrences all number
    6
    5
    2
    Dyspepsia
         subjects affected / exposed
    0 / 159 (0.00%)
    3 / 158 (1.90%)
    0 / 158 (0.00%)
         occurrences all number
    0
    3
    0
    Gastritis
         subjects affected / exposed
    2 / 159 (1.26%)
    2 / 158 (1.27%)
    1 / 158 (0.63%)
         occurrences all number
    2
    2
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 159 (1.26%)
    2 / 158 (1.27%)
    1 / 158 (0.63%)
         occurrences all number
    2
    2
    1
    Gastrointestinal inflammation
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Gingival pain
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Glossitis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Glossodynia
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Haematemesis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Haematochezia
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    1
    1
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Nausea
         subjects affected / exposed
    1 / 159 (0.63%)
    3 / 158 (1.90%)
    1 / 158 (0.63%)
         occurrences all number
    1
    3
    1
    Oral mucosa erosion
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Oral mucosal erythema
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Vomiting
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Salivary gland enlargement
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Actinic cheilitis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Asteatosis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Alopecia
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    1 / 158 (0.63%)
         occurrences all number
    0
    2
    1
    Dermatitis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    2 / 158 (1.27%)
         occurrences all number
    0
    0
    2
    Dermatitis contact
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    0 / 158 (0.00%)
         occurrences all number
    0
    3
    0
    Drug eruption
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Dry skin
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    2
    Eczema nummular
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Erythema
         subjects affected / exposed
    1 / 159 (0.63%)
    3 / 158 (1.90%)
    2 / 158 (1.27%)
         occurrences all number
    1
    3
    2
    Ingrowing nail
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Nail bed inflammation
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    0 / 158 (0.00%)
         occurrences all number
    0
    2
    0
    Photosensitivity reaction
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    2 / 158 (1.27%)
         occurrences all number
    0
    2
    2
    Pruritus generalised
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Psoriasis
         subjects affected / exposed
    5 / 159 (3.14%)
    1 / 158 (0.63%)
    2 / 158 (1.27%)
         occurrences all number
    7
    1
    2
    Pustular psoriasis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Rash
         subjects affected / exposed
    1 / 159 (0.63%)
    3 / 158 (1.90%)
    1 / 158 (0.63%)
         occurrences all number
    1
    3
    1
    Rash macular
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Rash pruritic
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Scar pain
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Skin erosion
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Seborrhoeic dermatitis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Skin ulcer
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Skin fissures
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Urticaria
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Xeroderma
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Haematuria
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    1
    Nephrolithiasis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Renal cyst
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Renal impairment
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Urinary incontinence
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Hyperthyroidism
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Hypothyroidism
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    2
    Arthralgia
         subjects affected / exposed
    1 / 159 (0.63%)
    8 / 158 (5.06%)
    4 / 158 (2.53%)
         occurrences all number
    1
    10
    4
    Back pain
         subjects affected / exposed
    4 / 159 (2.52%)
    3 / 158 (1.90%)
    0 / 158 (0.00%)
         occurrences all number
    4
    3
    0
    Bone pain
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Bursitis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Dactylitis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Muscle contracture
         subjects affected / exposed
    2 / 159 (1.26%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    2
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Muscular weakness
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    2 / 158 (1.27%)
         occurrences all number
    1
    1
    2
    Musculoskeletal pain
         subjects affected / exposed
    1 / 159 (0.63%)
    2 / 158 (1.27%)
    0 / 158 (0.00%)
         occurrences all number
    1
    2
    0
    Neck pain
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Osteoarthritis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Osteopenia
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 159 (0.63%)
    3 / 158 (1.90%)
    1 / 158 (0.63%)
         occurrences all number
    1
    4
    1
    Psoriatic arthropathy
         subjects affected / exposed
    5 / 159 (3.14%)
    4 / 158 (2.53%)
    1 / 158 (0.63%)
         occurrences all number
    5
    4
    1
    Spinal pain
         subjects affected / exposed
    2 / 159 (1.26%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    2
    0
    0
    Synovial cyst
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    1
    Tendonitis
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    1
    1
    1
    Tendon pain
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    2
    Angular cheilitis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    2 / 158 (1.27%)
         occurrences all number
    0
    0
    2
    Candida infection
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Bronchitis
         subjects affected / exposed
    4 / 159 (2.52%)
    5 / 158 (3.16%)
    5 / 158 (3.16%)
         occurrences all number
    5
    5
    6
    Cellulitis
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    1
    1
    1
    Chronic tonsillitis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Chronic sinusitis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    1 / 158 (0.63%)
         occurrences all number
    0
    2
    1
    Conjunctivitis bacterial
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Cutaneous tuberculosis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Cystitis
         subjects affected / exposed
    1 / 159 (0.63%)
    2 / 158 (1.27%)
    2 / 158 (1.27%)
         occurrences all number
    1
    2
    2
    Diarrhoea infectious
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Diverticulitis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Ear infection
         subjects affected / exposed
    0 / 159 (0.00%)
    3 / 158 (1.90%)
    2 / 158 (1.27%)
         occurrences all number
    0
    3
    2
    Fungal skin infection
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    2 / 158 (1.27%)
         occurrences all number
    0
    2
    2
    Eyelid infection
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Gastroenteritis
         subjects affected / exposed
    3 / 159 (1.89%)
    3 / 158 (1.90%)
    1 / 158 (0.63%)
         occurrences all number
    3
    3
    1
    Gastroenteritis viral
         subjects affected / exposed
    0 / 159 (0.00%)
    3 / 158 (1.90%)
    0 / 158 (0.00%)
         occurrences all number
    0
    3
    0
    Gastroenteritis aeromonas
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Helicobacter gastritis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Genital infection fungal
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Helicobacter infection
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Herpes zoster
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    1
    Hordeolum
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    0 / 158 (0.00%)
         occurrences all number
    0
    2
    0
    Influenza
         subjects affected / exposed
    2 / 159 (1.26%)
    1 / 158 (0.63%)
    2 / 158 (1.27%)
         occurrences all number
    2
    1
    2
    Laryngitis
         subjects affected / exposed
    2 / 159 (1.26%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    2
    0
    0
    Laryngitis viral
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Lyme disease
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 159 (1.26%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    2
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    16 / 159 (10.06%)
    25 / 158 (15.82%)
    22 / 158 (13.92%)
         occurrences all number
    22
    28
    25
    Oral candidiasis
         subjects affected / exposed
    2 / 159 (1.26%)
    0 / 158 (0.00%)
    2 / 158 (1.27%)
         occurrences all number
    2
    0
    2
    Oral herpes
         subjects affected / exposed
    4 / 159 (2.52%)
    0 / 158 (0.00%)
    4 / 158 (2.53%)
         occurrences all number
    4
    0
    4
    Oral infection
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Otitis media
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Paronychia
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    2 / 158 (1.27%)
         occurrences all number
    0
    2
    2
    Pharyngitis
         subjects affected / exposed
    3 / 159 (1.89%)
    4 / 158 (2.53%)
    2 / 158 (1.27%)
         occurrences all number
    3
    4
    2
    Pneumonia
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Pulpitis dental
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Rash pustular
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    2 / 158 (1.27%)
         occurrences all number
    1
    0
    2
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    1
    Rhinitis
         subjects affected / exposed
    6 / 159 (3.77%)
    0 / 158 (0.00%)
    4 / 158 (2.53%)
         occurrences all number
    6
    0
    5
    Sinusitis
         subjects affected / exposed
    7 / 159 (4.40%)
    2 / 158 (1.27%)
    2 / 158 (1.27%)
         occurrences all number
    8
    3
    2
    Skin bacterial infection
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Sinusitis bacterial
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 159 (0.00%)
    2 / 158 (1.27%)
    0 / 158 (0.00%)
         occurrences all number
    0
    2
    0
    Skin candida
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Subcutaneous abscess
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    2
    Tinea pedis
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Tonsillitis
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    1
    1
    1
    Tooth abscess
         subjects affected / exposed
    2 / 159 (1.26%)
    2 / 158 (1.27%)
    1 / 158 (0.63%)
         occurrences all number
    2
    2
    1
    Upper respiratory tract infection
         subjects affected / exposed
    10 / 159 (6.29%)
    8 / 158 (5.06%)
    7 / 158 (4.43%)
         occurrences all number
    12
    9
    9
    Tooth infection
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Upper respiratory tract infection bacterial
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Vaginal infection
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Urinary tract infection
         subjects affected / exposed
    4 / 159 (2.52%)
    1 / 158 (0.63%)
    3 / 158 (1.90%)
         occurrences all number
    4
    1
    3
    Viral infection
         subjects affected / exposed
    1 / 159 (0.63%)
    1 / 158 (0.63%)
    2 / 158 (1.27%)
         occurrences all number
    1
    1
    2
    Viral sinusitis
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    2
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Diabetes mellitus
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    1 / 158 (0.63%)
         occurrences all number
    0
    1
    1
    Electrolyte imbalance
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0
    Fructose intolerance
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Gout
         subjects affected / exposed
    1 / 159 (0.63%)
    3 / 158 (1.90%)
    0 / 158 (0.00%)
         occurrences all number
    1
    3
    0
    Hypercalcaemia
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 159 (0.63%)
    2 / 158 (1.27%)
    1 / 158 (0.63%)
         occurrences all number
    1
    2
    1
    Hyperkalaemia
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Hyperlipidaemia
         subjects affected / exposed
    0 / 159 (0.00%)
    3 / 158 (1.90%)
    1 / 158 (0.63%)
         occurrences all number
    0
    3
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    1
    0
    1
    Hyperuricaemia
         subjects affected / exposed
    1 / 159 (0.63%)
    2 / 158 (1.27%)
    1 / 158 (0.63%)
         occurrences all number
    1
    2
    1
    Impaired fasting glucose
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Lactose intolerance
         subjects affected / exposed
    0 / 159 (0.00%)
    1 / 158 (0.63%)
    0 / 158 (0.00%)
         occurrences all number
    0
    1
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 159 (0.00%)
    0 / 158 (0.00%)
    1 / 158 (0.63%)
         occurrences all number
    0
    0
    1
    Vitamin D deficiency
         subjects affected / exposed
    1 / 159 (0.63%)
    0 / 158 (0.00%)
    0 / 158 (0.00%)
         occurrences all number
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Mar 2014
    Based on the identification, from other studies of suicidal behavior and suicidal ideation reported in brodalumab psoriasis studies, the Columbia Suicide Severity Rating (C-SSRS) and the Patient Health Questionnaire depression scale (PHQ-8) were added as instruments to assess subject eligibility and monitor subject safety (ie, stopping rules). Other minor editorial were made.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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