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    Clinical Trial Results:
    A Phase 3, Multicenter, Randomized, Double-blind, Placebo and Active Comparator-controlled Study Evaluating the Efficacy and Safety of Guselkumab for the Treatment of Subjects with Moderate to Severe Plaque-type Psoriasis

    Summary
    EudraCT number
    2014-000719-15
    Trial protocol
    DE   HU   PL   ES  
    Global end of trial date
    17 Jun 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    01 Jul 2021
    First version publication date
    01 Jul 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CNTO1959PSO3001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02207231
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Janssen Pharmaceutical
    Sponsor organisation address
    1400 McKean Rd., Spring House, United States,
    Public contact
    Clinical Registry Group, Janssen Research and Development, LLC, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group, Janssen Research and Development, LLC, ClinicalTrialsEU@its.jnj.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
    17 Jun 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Jun 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objectives of this study were to evaluate the efficacy, safety, and tolerability of guselkumab in the treatment of subjects with moderate to severe plaque-type psoriasis.
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. The safety and tolerability of guselkumab and adalimumab were monitored by collecting information on adverse events (AEs), including injection-site reactions (ISRs) and allergic reactions, clinical laboratory tests, physical examinations, vital signs, electrocardiograms (ECGs), concomitant medication review, and early detection of active tuberculosis (TB).
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    03 Dec 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
    Australia: 57
    Country: Number of subjects enrolled
    Canada: 122
    Country: Number of subjects enrolled
    Korea, Republic of: 28
    Country: Number of subjects enrolled
    Russian Federation: 118
    Country: Number of subjects enrolled
    Taiwan: 73
    Country: Number of subjects enrolled
    United States: 170
    Country: Number of subjects enrolled
    Germany: 107
    Country: Number of subjects enrolled
    Hungary: 30
    Country: Number of subjects enrolled
    Poland: 107
    Country: Number of subjects enrolled
    Spain: 25
    Worldwide total number of subjects
    837
    EEA total number of subjects
    269
    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)
    793
    From 65 to 84 years
    43
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 1036 subjects were screened. Of these 1036 subjects, 837 subjects were enrolled and 836 were treated.

    Period 1
    Period 1 title
    Placebo Controlled Period: Week 0 - 16
    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
    Subjects received placebo matched to guselkumab subcutaneous (SC) injection at Weeks 0, 4, and 12, and placebo matched to adalimumab (2 SC injections) at Week 0, followed by placebo matched to adalimumab (1 SC injection) at Weeks 1, 3, and 5 and once every 2 weeks (q2w) thereafter through Week 15 in the placebo controlled period (PCP).
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo (for guselkumab)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matching to guselkumab was administered subcutaneously at Weeks 0, 4 and 12.

    Investigational medicinal product name
    Placebo (for adalimumab)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matching to adalimumab was administered subcutaneously (2 doses) at Week 0 followed by single subcutaneous dose at Weeks 1, 3 and 5 once q2w through Week 15.

    Arm title
    Guselkumab 100 mg
    Arm description
    Subjects received guselkumab 100 mg SC injection at Weeks 0, 4, and 12 and placebo matched to guselkumab SC injection at Week 16, and placebo matched to adalimumab (2 SC injections) at Week 0 followed by placebo matched to adalimumab (1 SC injection) at Weeks 1, 3, and 5 and q2w thereafter through Week 15.
    Arm type
    Experimental

    Investigational medicinal product name
    Guselkumab
    Investigational medicinal product code
    Other name
    CNTO1959
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Guselkumab 100 mg was administered subcutaneously at Weeks 0, 4, and 12.

    Arm title
    Adalimumab Then Guselkumab 100 mg
    Arm description
    Subjects received adalimumab 80 mg (2 SC injections) at Week 0 and adalimumab 40 mg (1 SC injection) at Weeks 1, 3, 5 and once q2w thereafter through Week 15 and placebo matched to guselkumab SC injection at Weeks 0, 4, 12.
    Arm type
    Active comparator

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Adalimumab 80 mg was administered subcutaneously (2 doses) at Week 0 followed by single subcutaneous dose of adalimumab 40 mg at Weeks 1, 3, 5, and once q2w through Week 15.

    Number of subjects in period 1
    Placebo Guselkumab 100 mg Adalimumab Then Guselkumab 100 mg
    Started
    174
    329
    334
    Treated
    174
    329
    333
    Completed
    167
    322
    324
    Not completed
    7
    7
    10
         Protocol deviation
    -
    -
    1
         Non-compliance with study drug
    -
    2
    1
         Lack of efficacy
    2
    -
    1
         Adverse event, non-fatal
    2
    4
    2
         Consent withdrawn by subject
    2
    -
    4
         Lost to follow-up
    1
    1
    1
    Period 2
    Period 2 title
    Active Controlled Period: Week 16 - 48
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo Then Guselkumab 100 mg
    Arm description
    Subjects receiving placebo crossed over to receive guselkumab 100 mg SC injection at Weeks 16 and 20 and once q8w thereafter through Week 44 and placebo matched to adalimumab SC injection at Weeks 17, 19, 21, and 23 and q2w thereafter through Week 47 in the active controlled period (ACP).
    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
    Placebo matching to adalimumab was administered subcutaneously at Weeks 17, 19, 21, 23, and q2w through Week 47.

    Investigational medicinal product name
    Guselkumab
    Investigational medicinal product code
    Other name
    CNTO1959
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Guselkumab 100 mg was administered subcutaneously to subjects receiving matching placebo in PCP and crossed over to receive guselkumab in ACP.

    Arm title
    Guselkumab 100 mg (ACP)
    Arm description
    Subjects received guselkumab 100 mg SC injection at Weeks 0, 4, and 12 and once q8w 8 weeks thereafter through Week 44, placebo matched to guselkumab SC injection at Week 16, and placebo matched to adalimumab (2 SC injections) at Week 0 followed by placebo matched to adalimumab (1 SC injection) at Weeks 1, 3, and 5 and q2w thereafter through Week 47.
    Arm type
    Experimental

    Investigational medicinal product name
    Guselkumab
    Investigational medicinal product code
    Other name
    CNTO1959
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Guselkumab 100 mg was administered subcutaneously q8w in ACP to subjects initially receiving guselkumab 100 mg in PCP.

    Arm title
    Adalimumab (ACP)
    Arm description
    Subjects received adalimumab 80 mg (2 SC injections) at Week 0 and adalimumab 40 mg (1 SC injection) at Weeks 1, 3, 5 and once q2w thereafter through Week 47 and placebo matched to guselkumab SC injection at Weeks 0, 4, 12, 16, 20 and once q8w thereafter through Week 44.
    Arm type
    Active comparator

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Adalimumab 40 mg was administered to subcutaneously q2w in ACP to subjects who were initially receiving adalimumab in PCP.

    Number of subjects in period 2 [1]
    Placebo Then Guselkumab 100 mg Guselkumab 100 mg (ACP) Adalimumab (ACP)
    Started
    165
    322
    324
    Completed
    162
    301
    281
    Not completed
    3
    21
    43
         Protocol deviation
    -
    1
    -
         Non-compliance with study drug
    -
    3
    3
         Lack of efficacy
    -
    3
    11
         Pregnancy
    -
    -
    1
         Adverse event, non-fatal
    1
    6
    10
         Unspecified
    -
    2
    3
         Consent withdrawn by subject
    1
    4
    10
         Lost to follow-up
    1
    2
    5
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 2 subjects did not crossover from placebo to guselkumab.
    Period 3
    Period 3 title
    Open-label Guselkumab: Week 48 - 264
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Adalimumab Then Guselkumab 100 mg
    Arm description
    Subjects receiving adalimumab entered a washout period after their final dose of adalimumab at Week 47 and received guselkumab 100 mg SC q8w at Week 52 and thereafter through Week 252.
    Arm type
    Active comparator

    Investigational medicinal product name
    Guselkumab
    Investigational medicinal product code
    Other name
    CNTO1959
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Guselkumab 100 mg was administered subcutaneously at Week 52 and q8w through Week 252 in open-label period.

    Arm title
    Guselkumab Combined
    Arm description
    All subjects who received guselkumab 100 mg subcutaneously q8w at Week 52 and thereafter through Week 252.
    Arm type
    Experimental

    Investigational medicinal product name
    Guselkumab
    Investigational medicinal product code
    Other name
    CNTO1959
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Guselkumab 100 mg was administered subcutaneously at Week 52 and q8w through Week 252.

    Number of subjects in period 3
    Adalimumab Then Guselkumab 100 mg Guselkumab Combined
    Started
    280
    463
    Completed
    242
    380
    Not completed
    38
    83
         Lack of efficacy
    2
    4
         Pregnancy
    3
    7
         Adverse event, serious fatal
    1
    3
         Adverse event, non-fatal
    12
    19
         Unspecified
    4
    11
         Consent withdrawn by subject
    10
    28
         Lost to follow-up
    6
    11

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received placebo matched to guselkumab subcutaneous (SC) injection at Weeks 0, 4, and 12, and placebo matched to adalimumab (2 SC injections) at Week 0, followed by placebo matched to adalimumab (1 SC injection) at Weeks 1, 3, and 5 and once every 2 weeks (q2w) thereafter through Week 15 in the placebo controlled period (PCP).

    Reporting group title
    Guselkumab 100 mg
    Reporting group description
    Subjects received guselkumab 100 mg SC injection at Weeks 0, 4, and 12 and placebo matched to guselkumab SC injection at Week 16, and placebo matched to adalimumab (2 SC injections) at Week 0 followed by placebo matched to adalimumab (1 SC injection) at Weeks 1, 3, and 5 and q2w thereafter through Week 15.

    Reporting group title
    Adalimumab Then Guselkumab 100 mg
    Reporting group description
    Subjects received adalimumab 80 mg (2 SC injections) at Week 0 and adalimumab 40 mg (1 SC injection) at Weeks 1, 3, 5 and once q2w thereafter through Week 15 and placebo matched to guselkumab SC injection at Weeks 0, 4, 12.

    Reporting group values
    Placebo Guselkumab 100 mg Adalimumab Then Guselkumab 100 mg Total
    Number of subjects
    174 329 334 837
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    164 311 318 793
        From 65 to 84 years
    10 18 15 43
        85 years and over
    0 0 1 1
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    44.9 ± 12.9 43.9 ± 12.74 42.9 ± 12.58 -
    Title for Gender
    Units: subjects
        Female
    55 89 85 229
        Male
    119 240 249 608

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received placebo matched to guselkumab subcutaneous (SC) injection at Weeks 0, 4, and 12, and placebo matched to adalimumab (2 SC injections) at Week 0, followed by placebo matched to adalimumab (1 SC injection) at Weeks 1, 3, and 5 and once every 2 weeks (q2w) thereafter through Week 15 in the placebo controlled period (PCP).

    Reporting group title
    Guselkumab 100 mg
    Reporting group description
    Subjects received guselkumab 100 mg SC injection at Weeks 0, 4, and 12 and placebo matched to guselkumab SC injection at Week 16, and placebo matched to adalimumab (2 SC injections) at Week 0 followed by placebo matched to adalimumab (1 SC injection) at Weeks 1, 3, and 5 and q2w thereafter through Week 15.

    Reporting group title
    Adalimumab Then Guselkumab 100 mg
    Reporting group description
    Subjects received adalimumab 80 mg (2 SC injections) at Week 0 and adalimumab 40 mg (1 SC injection) at Weeks 1, 3, 5 and once q2w thereafter through Week 15 and placebo matched to guselkumab SC injection at Weeks 0, 4, 12.
    Reporting group title
    Placebo Then Guselkumab 100 mg
    Reporting group description
    Subjects receiving placebo crossed over to receive guselkumab 100 mg SC injection at Weeks 16 and 20 and once q8w thereafter through Week 44 and placebo matched to adalimumab SC injection at Weeks 17, 19, 21, and 23 and q2w thereafter through Week 47 in the active controlled period (ACP).

    Reporting group title
    Guselkumab 100 mg (ACP)
    Reporting group description
    Subjects received guselkumab 100 mg SC injection at Weeks 0, 4, and 12 and once q8w 8 weeks thereafter through Week 44, placebo matched to guselkumab SC injection at Week 16, and placebo matched to adalimumab (2 SC injections) at Week 0 followed by placebo matched to adalimumab (1 SC injection) at Weeks 1, 3, and 5 and q2w thereafter through Week 47.

    Reporting group title
    Adalimumab (ACP)
    Reporting group description
    Subjects received adalimumab 80 mg (2 SC injections) at Week 0 and adalimumab 40 mg (1 SC injection) at Weeks 1, 3, 5 and once q2w thereafter through Week 47 and placebo matched to guselkumab SC injection at Weeks 0, 4, 12, 16, 20 and once q8w thereafter through Week 44.
    Reporting group title
    Adalimumab Then Guselkumab 100 mg
    Reporting group description
    Subjects receiving adalimumab entered a washout period after their final dose of adalimumab at Week 47 and received guselkumab 100 mg SC q8w at Week 52 and thereafter through Week 252.

    Reporting group title
    Guselkumab Combined
    Reporting group description
    All subjects who received guselkumab 100 mg subcutaneously q8w at Week 52 and thereafter through Week 252.

    Subject analysis set title
    Adalimumab Then Guselkumab 100 mg
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects received adalimumab 80 mg (2 SC injections) at Week 0 and adalimumab 40 mg (1 SC injection) at Weeks 1, 3, 5 and once q2w thereafter through Week 47 and placebo matched to guselkumab SC injection at Weeks 0, 4, 12, 16, 20 and once q8w thereafter through Week 44. Subjects entered a washout period after their final dose of adalimumab at Week 47 and received guselkumab 100 mg SC q8w at Week 52 and thereafter through Week 252.

    Subject analysis set title
    Guselkumab Combined
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All subjects who crossed over to receive guselkumab 100 mg subcutaneously at Week 16 from placebo group and subjects who were randomized to guselkumab 100 mg group at Week 0. Placebo crossover subjects were included in the guselkumab column after crossover to guselkumab.

    Primary: Percentage of Subjects Who Achieved an Investigator's Global Assessment (IGA) Score of Cleared (0) or Minimal (1) in the Guselkumab Group Compared to the Placebo Group at Week 16

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    End point title
    Percentage of Subjects Who Achieved an Investigator's Global Assessment (IGA) Score of Cleared (0) or Minimal (1) in the Guselkumab Group Compared to the Placebo Group at Week 16 [1]
    End point description
    The IGA documents the investigator's assessment of the subject's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The subject's psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). Randomized analysis set include all subjects randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 16 or who did not come for evaluation at week 16 were considered nonresponders) was used to impute missing values.
    End point type
    Primary
    End point timeframe
    Week 16
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    Placebo Guselkumab 100 mg
    Number of subjects analysed
    174
    329
    Units: percentage of subjects
        number (not applicable)
    6.9
    85.1
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v Guselkumab 100 mg
    Number of subjects included in analysis
    503
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval

    Primary: Percentage of Subjects Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response in the Guselkumab Group Compared to the Placebo Group at Week 16

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    End point title
    Percentage of Subjects Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response in the Guselkumab Group Compared to the Placebo Group at Week 16 [2]
    End point description
    The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents subjects who achieved at least a 90 percent improvement from baseline in the PASI score. Randomized analysis set include all subjects randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 16 or who did not come for evaluation at week 16 were considered nonresponders) was used to impute missing values.
    End point type
    Primary
    End point timeframe
    Week 16
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    Placebo Guselkumab 100 mg
    Number of subjects analysed
    174
    329
    Units: percentage of subjects
        number (not applicable)
    2.9
    73.3
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo v Guselkumab 100 mg
    Number of subjects included in analysis
    503
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval

    Secondary: Percentage of Subjects Who Achieved an IGA Score of Cleared (0) in the Guselkumab Group Compared to the Adalimumab Group at Weeks 24 and 48

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    End point title
    Percentage of Subjects Who Achieved an IGA Score of Cleared (0) in the Guselkumab Group Compared to the Adalimumab Group at Weeks 24 and 48 [3]
    End point description
    The IGA documents the investigator's assessment of the subject's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The subject's psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). Randomized analysis set included all subjects randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 24 or 48 who did not come for evaluation at week 24 or 48 were considered nonresponders) was used to impute missing values.
    End point type
    Secondary
    End point timeframe
    Weeks 24 and 48
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    Guselkumab 100 mg Adalimumab Then Guselkumab 100 mg
    Number of subjects analysed
    329
    334
    Units: percentage of subjects
    number (not applicable)
        Week 24
    52.6
    29.3
        Week 48
    50.5
    25.7
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Week 24
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Week 48
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval

    Secondary: Percentage of Subjects Who Achieved an IGA Score of Cleared (0) or Minimal (1) in the Guselkumab Group Compared to the Adalimumab Group at Weeks 24 and 48

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    End point title
    Percentage of Subjects Who Achieved an IGA Score of Cleared (0) or Minimal (1) in the Guselkumab Group Compared to the Adalimumab Group at Weeks 24 and 48 [4]
    End point description
    The IGA documents the investigator's assessment of the subject's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The subject’s psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). Randomized analysis set included all subjects randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 24 or 48 or who did not come for evaluation at Week 24 or 48 were considered nonresponders) was used to impute missing values.
    End point type
    Secondary
    End point timeframe
    Weeks 24 and 48
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    Guselkumab 100 mg Adalimumab Then Guselkumab 100 mg
    Number of subjects analysed
    329
    334
    Units: percentage of subjects
    number (not applicable)
        Week 24
    84.2
    61.7
        Week 48
    80.5
    55.4
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Week 24
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Week 48
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval

    Secondary: Percentage of Subjects Who Achieved PASI 90 Response in the Guselkumab Group Compared to the Adalimumab Group at Weeks 24 and 48

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    End point title
    Percentage of Subjects Who Achieved PASI 90 Response in the Guselkumab Group Compared to the Adalimumab Group at Weeks 24 and 48 [5]
    End point description
    The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents subjects who achieved at least a 90 percent improvement from baseline in the PASI score. Randomized analysis set included all subjects randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 24 or 48 who did not come for evaluation at week 24 or 48 were considered nonresponders) was used to impute missing values.
    End point type
    Secondary
    End point timeframe
    Weeks 24 and 48
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    Guselkumab 100 mg Adalimumab Then Guselkumab 100 mg
    Number of subjects analysed
    329
    334
    Units: percentage of subjects
    number (not applicable)
        Week 24
    80.2
    53.0
        Week 48
    76.3
    47.9
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Week 24
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Week 48
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval

    Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 in the Guselkumab Group Compared to the Placebo Group

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    End point title
    Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 in the Guselkumab Group Compared to the Placebo Group [6]
    End point description
    The DLQI is a 10-item questionnaire that measures the impact of skin disease on subject's quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the subject's life; 2-6 = small effect on the subject's life; 7-12 = moderate effect on the subject's life; 13-18 = very large effect on the subject's life; 19-30 = extremely large effect on the subject's life. Higher scores indicate more impact on quality of life of subjects. This secondary endpoint was planned to include only the placebo and guselkumab arms. Randomized analysis set included all subjects who were randomized at Week 0 and had a baseline DLQI score.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    Placebo Guselkumab 100 mg
    Number of subjects analysed
    174
    329
    Units: units on a scale
        arithmetic mean (standard deviation)
    -0.6 ± 6.36
    -11.2 ± 7.24
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    p value is based on analysis of variance (ANOVA) model stratified by investigator site (pooled).
    Comparison groups
    Placebo v Guselkumab 100 mg
    Number of subjects included in analysis
    503
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANOVA
    Confidence interval

    Secondary: Percentage of Subjects Who Achieved an IGA Score of Cleared (0) or Minimal (1) in the Guselkumab Group Compared to the Adalimumab Group at Week 16

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    End point title
    Percentage of Subjects Who Achieved an IGA Score of Cleared (0) or Minimal (1) in the Guselkumab Group Compared to the Adalimumab Group at Week 16 [7]
    End point description
    The IGA documents the investigator's assessment of the subject's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The subject's psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). Randomized analysis set included all subjects randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 16 or who did not come for evaluation at week 16 were considered nonresponders) was used to impute missing values.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    Guselkumab 100 mg Adalimumab Then Guselkumab 100 mg
    Number of subjects analysed
    329
    334
    Units: percentage of subjects
        number (not applicable)
    85.1
    65.9
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    p value is based on 1-sided Mantel Haenszel (MH) Z-test adjusted for investigator site (pooled).
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [8]
    P-value
    < 0.001
    Method
    MH Z-test
    Parameter type
    Difference in Percentage
    Point estimate
    19.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    12.9
         upper limit
    25.7
    Notes
    [8] - non-inferiority margin= 10.0%
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    p value is based on the Cochran-Mantel-Haenszel chi-square test stratified by investigator site (pooled).
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval

    Secondary: Percentage of Subjects Who Achieved PASI 90 Response in the Guselkumab Group Compared to the Adalimumab Group at Week 16

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    End point title
    Percentage of Subjects Who Achieved PASI 90 Response in the Guselkumab Group Compared to the Adalimumab Group at Week 16 [9]
    End point description
    The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents subjects who achieved at least a 90 percent improvement from baseline in the PASI score. Randomized analysis set include all subjects randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 16 or who did not come for evaluation at week 16 were considered nonresponders) was used to impute missing values.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    Guselkumab 100 mg Adalimumab Then Guselkumab 100 mg
    Number of subjects analysed
    329
    334
    Units: percentage of subjects
        number (not applicable)
    73.3
    49.7
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    p value is based on 1-sided MH Z-test adjusted for investigator site (pooled).
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [10]
    P-value
    < 0.001
    Method
    MH Z-test
    Parameter type
    Difference in Percentage
    Point estimate
    24.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    17
         upper limit
    31
    Notes
    [10] - non-inferiority margin= 10.0%
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    p value is based on the Cochran-Mantel-Haenszel chi-square test stratified by investigator site (pooled).
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval

    Secondary: Percentage of Subjects Who Achieved PASI 75 Response in the Guselkumab Group Compared to the Adalimumab Group at Week 16

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    End point title
    Percentage of Subjects Who Achieved PASI 75 Response in the Guselkumab Group Compared to the Adalimumab Group at Week 16 [11]
    End point description
    The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 75 response represents subjects who achieved at least a 75 percent improvement from baseline in the PASI score. Randomized analysis set include all subjects randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 16 or who did not come for evaluation at week 16 were considered nonresponders) was used to impute missing values.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    Guselkumab 100 mg Adalimumab Then Guselkumab 100 mg
    Number of subjects analysed
    329
    334
    Units: percentage of subjects
        number (not applicable)
    91.2
    73.1
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    p value is based on 1-sided MH Z-test adjusted for investigator site (pooled).
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [12]
    P-value
    < 0.001
    Method
    MH Z-test
    Parameter type
    Difference in percentage
    Point estimate
    18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    12.4
         upper limit
    23.8
    Notes
    [12] - non-inferiority margin= 10%
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    p value is based on the Cochran-Mantel-Haenszel chi-square test stratified by investigator site (pooled).
    Comparison groups
    Guselkumab 100 mg v Adalimumab Then Guselkumab 100 mg
    Number of subjects included in analysis
    663
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval

    Secondary: Percentage of Subjects who Achieved a Scalp-specific Investigator's Global Assessment (ss-IGA) Score of 0 or 1 and at Least a 2-Grade Improvement From Baseline at Week 16 in the Guselkumab Group Compared to the Placebo Group

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    End point title
    Percentage of Subjects who Achieved a Scalp-specific Investigator's Global Assessment (ss-IGA) Score of 0 or 1 and at Least a 2-Grade Improvement From Baseline at Week 16 in the Guselkumab Group Compared to the Placebo Group [13]
    End point description
    The ss-IGA instrument is used to evaluate the disease severity of scalp psoriasis. The lesions were assessed in terms of the clinical signs of redness, thickness, and scaliness, which are scored on a 5-point scale ranging from 0 = absence of disease, 1 = very mild disease, 2 = mild disease, 3 = moderate disease, and 4 = severe disease. This secondary endpoint was planned to include only the placebo and guselkumab arms. Population analyzed included only randomized subjects at Week 0 who had an ss-IGA score greater than or equal to (>=) 2 at baseline. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 16
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    Placebo Guselkumab 100 mg
    Number of subjects analysed
    145
    277
    Units: percentage of subjects
        number (not applicable)
    14.5
    83.4
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    p value is based on the Cochran-Mantel-Haenszel chi-square test stratified by investigator site (pooled).
    Comparison groups
    Placebo v Guselkumab 100 mg
    Number of subjects included in analysis
    422
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval

    Secondary: Change From Baseline in Psoriasis Symptom and Sign Diary (PSSD) Symptom Score at Week 16 in the Guselkumab Group Compared to the Placebo Group

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    End point title
    Change From Baseline in Psoriasis Symptom and Sign Diary (PSSD) Symptom Score at Week 16 in the Guselkumab Group Compared to the Placebo Group [14]
    End point description
    The PSSD (24-hour version) is a patient-reported outcome (PRO) questionnaire designed and validated to measure the severity of psoriasis symptoms and signs for the assessment of treatment benefit. It consisted of 11 items covering symptoms (itch, pain, stinging, burning, and skin tightness) and patient-observable signs (skin dryness, cracking, scaling, shedding or flaking, redness, and bleeding) using 0 (absent) to 10 (worst imaginable) numerical rating scales for severity. Higher score indicates more severe disease. This secondary endpoint was planned to include only the placebo and guselkumab arms. PSSD analysis set included all subjects who had baseline PSSD scores as the average score of at least 4 days out of the 7 days prior to the Week 0 visit. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 16
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    Placebo Guselkumab 100 mg
    Number of subjects analysed
    129
    249
    Units: units on a scale
        arithmetic mean (standard deviation)
    -3.0 ± 19.56
    -41.9 ± 24.61
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    p value is based on ANOVA model stratified by investigator site (pooled).
    Comparison groups
    Placebo v Guselkumab 100 mg
    Number of subjects included in analysis
    378
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANOVA
    Confidence interval

    Secondary: Percentage of Subjects who Achieved a PSSD Symptom Score of 0 in the Guselkumab Group Compared to the Adalimumab Group at Week 24

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    End point title
    Percentage of Subjects who Achieved a PSSD Symptom Score of 0 in the Guselkumab Group Compared to the Adalimumab Group at Week 24
    End point description
    The PSSD (24-hour version) is a patient-reported outcome (PRO) questionnaire designed and validated to measure the severity of psoriasis symptoms and signs for the assessment of treatment benefit. It consisted of 11 items covering symptoms (itch, pain, stinging, burning, and skin tightness) and patient-observable signs (skin dryness, cracking, scaling, shedding or flaking, redness, and bleeding) using 0 (absent) to 10 (worst imaginable) numerical rating scales for severity. Higher score indicates more severe disease. PSSD analysis set included all those subjects who were randomized at Week 0 and had baseline PSSD score greater than 0. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Guselkumab 100 mg (ACP) Adalimumab (ACP)
    Number of subjects analysed
    248
    273
    Units: percentage of subjects
        number (not applicable)
    36.3
    21.6
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    p value is based on the Cochran-Mantel-Haenszel chi-square test stratified by investigator site (pooled).
    Comparison groups
    Guselkumab 100 mg (ACP) v Adalimumab (ACP)
    Number of subjects included in analysis
    521
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel chi-square test
    Confidence interval

    Secondary: Percentage of Subjects Who Achieved PASI 90 Response at Week 252

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    End point title
    Percentage of Subjects Who Achieved PASI 90 Response at Week 252
    End point description
    In PASI system, body is divided into 4 regions: head, trunk, upper and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score ranging from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. PASI produces a numeric score that can range from 0 to 72. Higher score= more severe disease. PASI 90 response signify subjects who achieved at least a 90 percent improvement from baseline in the PASI score. Population analyzed included subjects who were randomized at Week 0 and treated with guselkumab. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 252
    End point values
    Adalimumab Then Guselkumab 100 mg Guselkumab Combined
    Number of subjects analysed
    246
    391
    Units: percentage of subjects
        number (not applicable)
    82.5
    84.1
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved PASI 75 Response at Week 252

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    End point title
    Percentage of Subjects Who Achieved PASI 75 Response at Week 252
    End point description
    In PASI system, body is divided into 4 regions: head, trunk, upper and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score ranging from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. PASI produces a numeric score that can range from 0 to 72. Higher score= more severe disease. PASI 75 response signify subjects who achieved at least a 75 percent improvement from baseline in the PASI score. Population analyzed included subjects who were randomized at Week 0 and treated with guselkumab. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 252
    End point values
    Adalimumab Then Guselkumab 100 mg Guselkumab Combined
    Number of subjects analysed
    246
    391
    Units: percentage of subjects
        number (not applicable)
    93.1
    93.9
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved an IGA Score of Cleared (0) or Minimal (1) at Week 252

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    End point title
    Percentage of Subjects Who Achieved an IGA Score of Cleared (0) or Minimal (1) at Week 252
    End point description
    The IGA documents the investigator's assessment of the subject's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The subject's psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). Population analyzed included subjects who were randomized at Week 0 and treated with guselkumab. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 252
    End point values
    Adalimumab Then Guselkumab 100 mg Guselkumab Combined
    Number of subjects analysed
    246
    391
    Units: percentage of subjects
        number (not applicable)
    82.9
    82.4
    No statistical analyses for this end point

    Secondary: Percentage of Subjects with a DLQI Score of 0 or 1 at Week 252

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    End point title
    Percentage of Subjects with a DLQI Score of 0 or 1 at Week 252
    End point description
    DLQI measures impact of skin disease on subject's QoL. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much). DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1=no effect on subject's life; 2-6=small effect; 7-12=moderate effect; 13-18=very large effect; 19-30=extremely large effect. DLQI was calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. Higher scores indicate more impact on subject's QoL. Population analyzed included subjects randomized at Week 0 and treated with guselkumab with baseline DLQI score >1. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 252
    End point values
    Adalimumab Then Guselkumab 100 mg Guselkumab Combined
    Number of subjects analysed
    235
    347
    Units: percentage of subjects
        number (not applicable)
    74.0
    72.7
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With who Achieved a PSSD Symptom Score of 0 at Week 252

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    End point title
    Percentage of Subjects With who Achieved a PSSD Symptom Score of 0 at Week 252
    End point description
    The PSSD consisted of 11 items covering symptoms (itch, pain, stinging, burning, and skin tightness) and patient-observable signs (skin dryness, cracking, scaling, shedding or flaking, redness, and bleeding) using 0 (absent) to 10 (worst imaginable) numerical rating scales for severity. Higher score indicates more severe disease. Population analyzed included subjects who were randomized at Week 0 and treated with guselkumab with baseline PSSD symptom score >0. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 252
    End point values
    Adalimumab Then Guselkumab 100 mg Guselkumab Combined
    Number of subjects analysed
    200
    297
    Units: percentage of subjects
        number (not applicable)
    48.0
    42.4
    No statistical analyses for this end point

    Secondary: Percentage of Subjects who Achieved a PSSD Sign Score of 0 at Week 252

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    End point title
    Percentage of Subjects who Achieved a PSSD Sign Score of 0 at Week 252
    End point description
    The PSSD consisted of 11 items covering symptoms (itch, pain, stinging, burning, and skin tightness) and patient-observable signs (skin dryness, cracking, scaling, shedding or flaking, redness, and bleeding) using 0 (absent) to 10 (worst imaginable) numerical rating scales for severity. Higher score indicates more severe disease. Population analyzed included subjects who were randomized at Week 0 and treated with guselkumab with baseline PSSD sign score >0. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 252
    End point values
    Adalimumab Then Guselkumab 100 mg Guselkumab Combined
    Number of subjects analysed
    201
    297
    Units: percentage of subjects
        number (not applicable)
    37.8
    33.0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline (Week 0) up to Week 264
    Adverse event reporting additional description
    Safety analysis included all subjects who were randomized at Week 0 and received at least 1 dose of study agent (partial or complete). Subjects who discontinued in 1st period and had safety follow-up beyond Week 16, counted in both the periods for safety data.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Placebo (PCP)
    Reporting group description
    Subjects received placebo matched to guselkumab subcutaneous (SC) injection at Weeks 0, 4, and 12 during the placebo controlled period.

    Reporting group title
    Guselkumab 100 mg (PCP)
    Reporting group description
    Subjects received guselkumab 100 mg SC injection at Weeks 0, 4, and 12 during the placebo controlled period.

    Reporting group title
    Adalimumab (PCP)
    Reporting group description
    Subjects received adalimumab 80 mg (2 SC injections) at Week 0 and adalimumab 40 mg (1 SC injection) at Week 1 and once every other week thereafter through Week 15 during the placebo controlled period.

    Reporting group title
    Placebo Then Guselkumab 100 mg (ACP)
    Reporting group description
    Subjects initially randomized to placebo crossed over to receive guselkumab 100 milligram (mg) SC injection at Weeks 16 and 20 and once every 8 weeks thereafter through Week 44 in the active controlled period (ACP).

    Reporting group title
    Guselkumab 100 mg (ACP)
    Reporting group description
    Subjects received guselkumab 100 mg SC injection at Weeks 0, 4, and 12 and once every 8 weeks thereafter through Week 44, placebo matched to guselkumab SC injection at Week 16, and placebo matched to adalimumab (2 SC injections) at Week 0 followed by placebo matched to adalimumab (1 SC injections) at Weeks 1, 3, and 5 and every 2 weeks thereafter through Week 47.

    Reporting group title
    Adalimumab (ACP)
    Reporting group description
    Subjects received adalimumab 80 mg (2 SC injections) at Week 0 and adalimumab 40 mg (1 SC injection) at Weeks 1, 3, 5 and once every 2 weeks thereafter through Week 47 and placebo matched to guselkumab SC injection at Weeks 0, 4, 12, 16, 20 and once every 8 weeks thereafter through Week 44.

    Reporting group title
    Adalimumab then Guselkumab 100 mg (After ACP)
    Reporting group description
    Subjects initially randomized to adalimumab entered a washout period after their final dose at Week 47 and crossed over to receive guselkumab 100 mg subcutaneously q8w at Week 52 and thereafter through Week 252. This arm reports safety data for subjects that crossed over to guselkumab from adalimumab.

    Reporting group title
    Guselkumab Combined
    Reporting group description
    All subjects who crossed over to receive guselkumab 100 mg subcutaneously at Week 16 from placebo group and subjects who were randomized to guselkumab 100 mg group at Week 0. Placebo crossover subjects were included in the guselkumab column after crossover to guselkumab. Subjects that discontinued treatment prematurely were followed up for safety and hence were included in the safety data. Therefore, combined safety results are reported for this arm. This arm reports safety data for guselkumab.

    Serious adverse events
    Placebo (PCP) Guselkumab 100 mg (PCP) Adalimumab (PCP) Placebo Then Guselkumab 100 mg (ACP) Guselkumab 100 mg (ACP) Adalimumab (ACP) Adalimumab then Guselkumab 100 mg (After ACP) Guselkumab Combined
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 174 (1.72%)
    8 / 329 (2.43%)
    6 / 333 (1.80%)
    5 / 165 (3.03%)
    8 / 324 (2.47%)
    10 / 326 (3.07%)
    34 / 280 (12.14%)
    79 / 494 (15.99%)
         number of deaths (all causes)
    1
    3
    2
    1
    3
    2
    1
    4
         number of deaths resulting from adverse events
    Vascular disorders
    Aortic Aneurysm
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep Vein Thrombosis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive Crisis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral Arterial Occlusive Disease
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral Artery Stenosis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    1 / 333 (0.30%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis Superficial
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Astrocytoma
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    B-Cell Lymphoma
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder Cancer
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast Cancer
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    2 / 494 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon Cancer
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epiglottic Cancer
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Gastric Cancer
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive Papillary Breast Carcinoma
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    1 / 324 (0.31%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngeal Cancer
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lipoma
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant Melanoma
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant Melanoma in Situ
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary Cystadenoma Lymphomatosum
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate Cancer
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal Adenocarcinoma
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    2 / 494 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sarcoma
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine Leiomyoma
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    2 / 494 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion Missed
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abortion Spontaneous
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Hernia
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 329 (0.30%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Completed Suicide
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Psychotic Disorder
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 329 (0.30%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Substance Abuse
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal Ideation
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide Attempt
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    1 / 326 (0.31%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian Cyst Ruptured
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine Polyp
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    2 / 494 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Abdominal Injury
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle Fracture
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Avulsion Fracture
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical Vertebral Fracture
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    1 / 333 (0.30%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest Injury
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle Fracture
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 329 (0.30%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral Injury
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral Neck Fracture
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foreign Body
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus Fracture
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaw Fracture
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint Dislocation
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    1 / 326 (0.31%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament Rupture
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    2 / 494 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb Injury
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus Injury
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    1 / 165 (0.61%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple Injuries
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post Procedural Fistula
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    1 / 326 (0.31%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural Hypotension
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius Fracture
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    1 / 333 (0.30%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin Laceration
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft Tissue Injury
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal Fracture
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon Injury
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic Vertebral Fracture
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Human Chorionic Gonadotropin Increased
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute Myocardial Infarction
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    1 / 333 (0.30%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina Pectoris
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic Valve Incompetence
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac Failure
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    1 / 333 (0.30%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary Artery Disease
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial Infarction
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 329 (0.30%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    3 / 494 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial Ischaemia
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    1 / 326 (0.31%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus Node Dysfunction
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    1 / 165 (0.61%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Dermoid Cyst
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    1 / 324 (0.31%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Aspiration
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Oedema
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Sarcoidosis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Balance Disorder
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carpal Tunnel Syndrome
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular Accident
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Idiopathic Partial Epilepsy
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lacunar Infarction
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 329 (0.30%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Hernia
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal Ulcer
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocutaneous Fistula
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    1 / 324 (0.31%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    1 / 165 (0.61%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal Hernia
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal Strangulation
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large Intestine Polyp
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small Intestinal Obstruction
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical Hernia
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    1 / 324 (0.31%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    1 / 324 (0.31%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 329 (0.30%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary Retention
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    1 / 324 (0.31%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis Acute
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 329 (0.30%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis Acute
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    1 / 326 (0.31%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic Failure
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Ischaemic Hepatitis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    1 / 326 (0.31%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis Atopic
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis Contact
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythema Nodosum
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythrodermic Psoriasis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    1 / 326 (0.31%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lichen Planus
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    1 / 165 (0.61%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psoriasis
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back Pain
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    1 / 326 (0.31%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chondromalacia
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dupuytren's Contracture
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral Disc Degeneration
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral Disc Disorder
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral Disc Protrusion
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    2 / 494 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lateral Patellar Compression Syndrome
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscal Degeneration
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    1 / 165 (0.61%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metatarsalgia
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    2 / 280 (0.71%)
    3 / 494 (0.61%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator Cuff Syndrome
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 329 (0.30%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Trigger Finger
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal Abscess
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    1 / 326 (0.31%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess Limb
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    1 / 324 (0.31%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute Sinusitis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal Abscess
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    1 / 165 (0.61%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    2 / 326 (0.61%)
    0 / 280 (0.00%)
    4 / 494 (0.81%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    2 / 333 (0.60%)
    0 / 165 (0.00%)
    1 / 324 (0.31%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    3 / 494 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic Tonsillitis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian Abscess
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    1 / 280 (0.36%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Staphylococcal
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    1 / 326 (0.31%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Postoperative Wound Infection
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    1 / 324 (0.31%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    0 / 494 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scrotal Abscess
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicella
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    0 / 324 (0.00%)
    0 / 326 (0.00%)
    0 / 280 (0.00%)
    1 / 494 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Placebo (PCP) Guselkumab 100 mg (PCP) Adalimumab (PCP) Placebo Then Guselkumab 100 mg (ACP) Guselkumab 100 mg (ACP) Adalimumab (ACP) Adalimumab then Guselkumab 100 mg (After ACP) Guselkumab Combined
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    51 / 174 (29.31%)
    101 / 329 (30.70%)
    98 / 333 (29.43%)
    67 / 165 (40.61%)
    134 / 324 (41.36%)
    137 / 326 (42.02%)
    193 / 280 (68.93%)
    307 / 494 (62.15%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    4 / 174 (2.30%)
    10 / 329 (3.04%)
    7 / 333 (2.10%)
    6 / 165 (3.64%)
    5 / 324 (1.54%)
    10 / 326 (3.07%)
    17 / 280 (6.07%)
    40 / 494 (8.10%)
         occurrences all number
    4
    10
    7
    8
    6
    10
    17
    43
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 174 (0.57%)
    2 / 329 (0.61%)
    4 / 333 (1.20%)
    6 / 165 (3.64%)
    10 / 324 (3.09%)
    8 / 326 (2.45%)
    20 / 280 (7.14%)
    24 / 494 (4.86%)
         occurrences all number
    1
    2
    4
    6
    10
    8
    23
    30
    Nervous system disorders
    Headache
         subjects affected / exposed
    7 / 174 (4.02%)
    14 / 329 (4.26%)
    13 / 333 (3.90%)
    1 / 165 (0.61%)
    7 / 324 (2.16%)
    16 / 326 (4.91%)
    17 / 280 (6.07%)
    28 / 494 (5.67%)
         occurrences all number
    7
    14
    15
    1
    7
    16
    24
    42
    General disorders and administration site conditions
    Injection Site Erythema
         subjects affected / exposed
    1 / 174 (0.57%)
    6 / 329 (1.82%)
    17 / 333 (5.11%)
    3 / 165 (1.82%)
    4 / 324 (1.23%)
    11 / 326 (3.37%)
    7 / 280 (2.50%)
    5 / 494 (1.01%)
         occurrences all number
    1
    8
    35
    4
    9
    33
    35
    14
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 174 (1.15%)
    2 / 329 (0.61%)
    4 / 333 (1.20%)
    6 / 165 (3.64%)
    8 / 324 (2.47%)
    4 / 326 (1.23%)
    13 / 280 (4.64%)
    28 / 494 (5.67%)
         occurrences all number
    4
    2
    4
    6
    9
    4
    14
    40
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    10 / 174 (5.75%)
    5 / 329 (1.52%)
    7 / 333 (2.10%)
    0 / 165 (0.00%)
    3 / 324 (0.93%)
    6 / 326 (1.84%)
    7 / 280 (2.50%)
    16 / 494 (3.24%)
         occurrences all number
    13
    5
    7
    0
    3
    6
    8
    20
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 174 (1.72%)
    11 / 329 (3.34%)
    8 / 333 (2.40%)
    2 / 165 (1.21%)
    10 / 324 (3.09%)
    8 / 326 (2.45%)
    26 / 280 (9.29%)
    37 / 494 (7.49%)
         occurrences all number
    4
    13
    8
    2
    11
    8
    32
    43
    Back Pain
         subjects affected / exposed
    2 / 174 (1.15%)
    6 / 329 (1.82%)
    5 / 333 (1.50%)
    1 / 165 (0.61%)
    7 / 324 (2.16%)
    12 / 326 (3.68%)
    22 / 280 (7.86%)
    28 / 494 (5.67%)
         occurrences all number
    3
    6
    5
    1
    8
    13
    25
    37
    Psoriatic Arthropathy
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 329 (0.30%)
    0 / 333 (0.00%)
    0 / 165 (0.00%)
    1 / 324 (0.31%)
    0 / 326 (0.00%)
    14 / 280 (5.00%)
    12 / 494 (2.43%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    14
    14
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    2 / 174 (1.15%)
    2 / 329 (0.61%)
    3 / 333 (0.90%)
    5 / 165 (3.03%)
    4 / 324 (1.23%)
    7 / 326 (2.15%)
    19 / 280 (6.79%)
    23 / 494 (4.66%)
         occurrences all number
    2
    2
    3
    7
    4
    8
    19
    30
    Gastroenteritis
         subjects affected / exposed
    2 / 174 (1.15%)
    5 / 329 (1.52%)
    2 / 333 (0.60%)
    3 / 165 (1.82%)
    11 / 324 (3.40%)
    4 / 326 (1.23%)
    14 / 280 (5.00%)
    25 / 494 (5.06%)
         occurrences all number
    2
    5
    2
    3
    13
    5
    20
    31
    Influenza
         subjects affected / exposed
    0 / 174 (0.00%)
    2 / 329 (0.61%)
    2 / 333 (0.60%)
    1 / 165 (0.61%)
    2 / 324 (0.62%)
    2 / 326 (0.61%)
    16 / 280 (5.71%)
    20 / 494 (4.05%)
         occurrences all number
    0
    2
    2
    1
    2
    2
    16
    20
    Nasopharyngitis
         subjects affected / exposed
    17 / 174 (9.77%)
    30 / 329 (9.12%)
    36 / 333 (10.81%)
    34 / 165 (20.61%)
    65 / 324 (20.06%)
    57 / 326 (17.48%)
    89 / 280 (31.79%)
    148 / 494 (29.96%)
         occurrences all number
    19
    34
    42
    45
    89
    75
    190
    313
    Pharyngitis
         subjects affected / exposed
    0 / 174 (0.00%)
    0 / 329 (0.00%)
    2 / 333 (0.60%)
    1 / 165 (0.61%)
    5 / 324 (1.54%)
    7 / 326 (2.15%)
    17 / 280 (6.07%)
    18 / 494 (3.64%)
         occurrences all number
    0
    0
    2
    1
    5
    8
    20
    20
    Sinusitis
         subjects affected / exposed
    0 / 174 (0.00%)
    3 / 329 (0.91%)
    1 / 333 (0.30%)
    3 / 165 (1.82%)
    7 / 324 (2.16%)
    6 / 326 (1.84%)
    14 / 280 (5.00%)
    19 / 494 (3.85%)
         occurrences all number
    0
    3
    1
    3
    7
    6
    16
    26
    Upper Respiratory Tract Infection
         subjects affected / exposed
    9 / 174 (5.17%)
    25 / 329 (7.60%)
    16 / 333 (4.80%)
    17 / 165 (10.30%)
    31 / 324 (9.57%)
    33 / 326 (10.12%)
    69 / 280 (24.64%)
    107 / 494 (21.66%)
         occurrences all number
    9
    32
    18
    24
    38
    41
    119
    222

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Feb 2015
    Amendment-1 included the following major changes: to address the regulatory, ethics committee, and investigator feedback. The key changes done ensured consistency in the assessments and the timepoints across all the guselkumab Phase 3 psorias protocols. The major changes were additional timepoints for antibody assessments were added to the Time and Events Schedule; The secondary objective was corrected to delete the mention of health economics outcomes, which were not actually collected in this study; Body surface area (BSA) assessment at Week 48 was deleted; physical examination was added at Week 148 and deleted at Weeks 60, 68, and 76; and weight measurement was added at Week 160; The follow-up visits and time frames for subjects who discontinued study treatment before the last scheduled injection were revised; Information was added about the presence of dry natural rubber on the adalimumab prefilled syringe (PFS) needle cover; The inclusion criteria for female subjects of childbearing potential and male subjects who were sexually active with women of childbearing potential were clarified to indicate that barrier methods should be used with a spermicidal agent if spermicidal agents were available in the subjects’ locale; The exclusion criterion for major surgery was clarified, and an exclusion criterion was added to exclude Sponsor employees from participation in the study; The dosage and administration description for Group II was revised to clarify administrations after Week 16; The time point after which antimalarial agents could be used was corrected to Week 48 (from Week 52); and the study visit for assessments for subjects who withdrew from study participation after Week 48 was corrected to Week 148 (from Week 160).
    04 Apr 2017
    Amendment-3 included the following major change: the duration of open-label treatment period by 2 years thereby changing the final study visit (end of study) from Week 160 to Week 264 (5 years).

    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.
    All subjects were on guselkumab after Week 48; therefore, there was no concurrent control group within the study after Week 48.
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