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    Clinical Trial Results:
    A Multicenter, Randomized, Double-Blind, Secukinumab-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Bimekizumab in Adult Subjects With Moderate to Severe Chronic Plaque Psoriasis

    Summary
    EudraCT number
    		 2017-003784-35
    Trial protocol
    		 DE   GB   BE   NL   PL   ES  
    Global end of trial date
    09 Aug 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Aug 2024
    First version publication date
    23 Aug 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    PS0015
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03536884
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    UCB Biopharma SRL
    Sponsor organisation address
    Allée de la Recherche 60, Brussels, Belgium, 1070
    Public contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
    Scientific contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.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
    11 Sep 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Sep 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Aug 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Compare the efficacy of bimekizumab versus secukinumab at achieving complete clearance (PASI100) in subjects with moderate to severe chronic plaque psoriasis (PSO).
    Protection of trial subjects
    During the conduct of the study all participants were closely monitored.
    Background therapy
    		 Background therapy as permitted in the protocol.
    Evidence for comparator
    		 Bimekizumab is a humanized, full-length monoclonal antibody (mAb) of the immunoglobulin G1 subclass with 2 identical antigen binding regions that potently and selectively bind and neutralize IL-17A, IL-17F, and IL-17AF cytokines. This property makes bimekizumab distinct from other IL‑17-targeting agents, like secukinumab and ixekizumab (selective anti IL‑17A cytokine-targeting mAbs). Antibodies targeting IL-17A cytokines have demonstrated efficacy in patients with PSO, psoriatic arthritis (PsA), and ankylosing spondylitis. As shown in human in vitro immune mediated disease models, dual neutralization of both IL-17A and IL-17F like with bimekizumab was superior to neutralization of IL-17A alone (Glatt et al, 2018). In a Phase 3 study in patients with PSO, inhibition of both IL-17A and IL-17F with bimekizumab was shown to be therapeutically superior to inhibition of IL-17A alone (Reich et al, 2021). The primary objective of this study was to compare the efficacy of bimekizumab administered sc for 16 weeks versus secukinumab at achieving complete clearance (100% improvement in the PASI score [PASI100]) in study participants with moderate to severe chronic plaque PSO.
    Actual start date of recruitment
    13 Jun 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 99
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    Poland: 255
    Country: Number of subjects enrolled
    Spain: 23
    Country: Number of subjects enrolled
    Türkiye: 18
    Country: Number of subjects enrolled
    United Kingdom: 8
    Country: Number of subjects enrolled
    United States: 203
    Country: Number of subjects enrolled
    Australia: 27
    Country: Number of subjects enrolled
    Belgium: 6
    Country: Number of subjects enrolled
    Canada: 88
    Country: Number of subjects enrolled
    France: 11
    Worldwide total number of subjects
    743
    EEA total number of subjects
    399
    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)
    666
    From 65 to 84 years
    76
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study started to enroll participants in June 2018 and concluded in August 2023. Study has Screening Period (2-5 weeks (wk)), DB Treatment Period 48 wks (ITP-Wk 0-16 and MTP- Wk 16-Wk 48), an optional OLE Period (96 wks) followed by SFU Visit (20 wks after final dose) and an optional OLE2 Period followed by SFU2 Visit (20 wks after final dose).

    Pre-assignment
    Screening details
    		 Participant flow refers to the Randomized Set (RS), Maintenance Set (MS), Open-Label Set (OLS), and Open-Label Set 2 (OLS2).

    Period 1
    Period 1 title
    Double-Blind (DB) Period: ITP Wk 0-16
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ITP: Bimekizumab (BKZ) 320 milligrams (mg) Q4W
    Arm description
    		 Participants randomized to this arm received BKZ 320 mg subcutaneously (sc) every 4 weeks (Q4W) for 16 weeks in the Initial Treatment Period (ITP). Placebo was administered at pre-specified time-points to maintain the blinding.
    Arm type
    		 Experimental

    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
    Participants received placebo at pre-specified time-points to maintain the blinding.

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Bimzelx®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 320 mg at pre-specified time-points.

    Arm title
    		 ITP: Secukinumab 300 mg Q4W
    Arm description
    		 Participants received secukinumab 300 mg sc at Baseline and Weeks 1, 2, 3, and 4 followed by dosing Q4W until Week 16 in the Initial Treatment Period.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Secukinumab
    Investigational medicinal product code
    Other name
    COSENTYX®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received secukinumab 300 mg at pre-specified time-points.

    Number of subjects in period 1
    		ITP: Bimekizumab (BKZ) 320 milligrams (mg) Q4W ITP: Secukinumab 300 mg Q4W
    Started
    373
    370
    Completed
    362
    354
    Not completed
    11
    16
         Unable to attend visits
    -
    1
         Consent withdrawn by subject
    3
    4
         Adverse event, non-fatal
    8
    6
         Withdrawn by Investigator for abnormal lab values
    -
    1
         Unblinding was reason for dropout
    -
    1
         Lost to follow-up
    -
    3
    Period 2
    Period 2 title
    Double-Blind Period: MTP Wk 16-48
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MTP: BKZ 320 mg Q4W/Q8W
    Arm description
    		 Participants randomized to this arm received BKZ 320 mg sc Q4W for 16 weeks in the Initial Treatment Period. At Week 16, participants were re-randomized to receive bimekizumab 320 mg sc Q8W until Week 48 in the Maintenance Treatment Period (MTP). Placebo was administered at pre-specified time-points to maintain the blinding.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Bimzelx®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 320 mg at pre-specified time-points.

    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
    Participants received placebo at pre-specified time-points to maintain the blinding.

    Arm title
    		 MTP: BKZ 320 mg Q4W/Q4W
    Arm description
    		 Participants randomized to this arm received BKZ 320 mg sc Q4W for 16 weeks in the Initial Treatment Period. At Week 16, participants continued to receive BKZ 320 mg sc every 4 Weeks (Q4W/Q4W) until Week 48 in the Maintenance Treatment Period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Bimzelx®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 320 mg at pre-specified time-points.

    Arm title
    		 MTP: Secukinumab 300 mg Q4W/Q4W
    Arm description
    		 Participants in secukinumab arm continued to receive secukinumab 300 mg sc Q4W until Week 48 in the Maintenance Treatment Period.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Secukinumab
    Investigational medicinal product code
    Other name
    COSENTYX®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received secukinumab 300 mg at pre-specified time-points.

    Number of subjects in period 2
    		MTP: BKZ 320 mg Q4W/Q8W MTP: BKZ 320 mg Q4W/Q4W MTP: Secukinumab 300 mg Q4W/Q4W
    Started
    215
    147
    354
    Completed
    205
    138
    325
    Not completed
    10
    9
    29
         Adverse event, serious fatal
    1
    -
    1
         Consent withdrawn by subject
    7
    3
    12
         Adverse event, non-fatal
    1
    3
    3
         Lost to follow-up
    1
    2
    9
         Lack of efficacy
    -
    1
    4
    Period 3
    Period 3 title
    OLE Period: Wk48-Wk144
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 OLE Period: BKZ Week 0-48/BKZ Q8W 320 mg
    Arm description
    		 Participants randomized to this arm received BKZ 320 mg sc Q4W for the first 16 weeks and then re-randomized to receive BKZ 320 mg sc Q4W or Q8W until Week 48 of the double-blind Treatment Period. Based on the PASI90 response and the dose the participant was receiving at Week 48, participants were randomized to receive BKZ 320 mg sc Q8W until Week 136 in the Open-Label Extension (OLE) Period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Bimzelx®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 320 mg at pre-specified time-points.

    Arm title
    		 OLE Period: BKZ Week 0-48/ BKZ Q4W 320 mg
    Arm description
    		 Participants randomized to this arm received BKZ 320 mg sc Q4W for the first 16 weeks and then re-randomized to receive BKZ 320 mg sc Q4W or Q8W until Week 48 of the double-blind Treatment Period. Based on the PASI90 response and the dose the participant was receiving at Week 48, participants were randomized to receive BKZ 320 mg sc Q4W starting in OLE Period. The participant’s dosing interval was changed from BKZ 320mg Q4W to BKZ 320mg Q8W at Week 64, or at the next scheduled clinic visit if the participant has already completed the Week 64 after protocol amendment 5.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Bimzelx®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 320 mg at pre-specified time-points.

    Arm title
    		 OLE Period: Secukinumab Week 0-48/ BKZ Q8W 320 mg
    Arm description
    		 Participants randomized to this arm received Secukinumab 300 mg sc Q4W until Week 48 of the double-blind Treatment Period. Based on the PASI90 response in double-blind Treatment Period, participants randomized to receive BKZ 320 mg sc Q8W until Week 136 of the OLE Period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Bimzelx®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 320 mg at pre-specified time-points.

    Arm title
    		 OLE Period: Secukinumab Week 0-48/ BKZ Q4W 320 mg
    Arm description
    		 Participants randomized to this arm received Secukinumab 300 mg sc Q4W until Week 48 of the double-blind Treatment Period. Based on the PASI90 response in double-blind Treatment Period, participants randomized to receive BKZ 320 mg sc Q4W starting in OLE Period. The participant’s dosing interval was changed from BKZ 320mg Q4W to BKZ 320mg Q8W at Week 64, or at the next scheduled clinic visit if the participant has already completed the Week 64 after protocol amendment 5.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Bimzelx®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 320 mg at pre-specified time-points.

    Number of subjects in period 3 [1]
    		OLE Period: BKZ Week 0-48/BKZ Q8W 320 mg OLE Period: BKZ Week 0-48/ BKZ Q4W 320 mg OLE Period: Secukinumab Week 0-48/ BKZ Q8W 320 mg OLE Period: Secukinumab Week 0-48/ BKZ Q4W 320 mg
    Started
    238
    98
    122
    196
    Completed
    205
    80
    106
    167
    Not completed
    33
    18
    16
    29
         Consent withdrawn by subject
    12
    7
    6
    6
         She wants to be pregnant
    -
    -
    -
    1
         Adverse event, non-fatal
    10
    8
    6
    13
         Not dosing for over 6 Months while out of country
    1
    -
    -
    -
         Non-compliance
    1
    -
    -
    -
         Went to jail, unable to continue study visits
    -
    1
    -
    -
         Patient held IP due to pandemic, not restarted
    -
    1
    -
    -
         Lost to follow-up
    7
    -
    1
    5
         Lack of efficacy
    1
    1
    1
    4
         Protocol deviation
    1
    -
    2
    -
    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: Participants who provided consent to continue in OLE Period.
    Period 4
    Period 4 title
    OLE2 Period: Wk 144/OLE2 BL- OLE2 Wk 48
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 OLE2 Period - Group A: BKZ 320 mg Q8W
    Arm description
    		 Participants who were still receiving treatment in the OLE Period and attended the Week 144 visit were directly rolled over to the OLE2 Period. In OLE2 Period, participants continued receiving BKZ 320 mg sc Q8W for 40 additional weeks until OLE2 Week 48.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Bimzelx®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 320 mg at pre-specified time-points.

    Arm title
    		 OLE2 Period - Group B: BKZ 320 mg Q8W
    Arm description
    		 Participants who completed the Week 144 and were participating in the Safety Follow-Up (SFU) or had completed the SFU visit reinitiated their treatment in the OLE2 Period after having undergone Screening assessments during a 4-week OLE2 Screening Period. Participants with an IGA score less than (<) 3 at the Week 144/OLE2 Baseline Visit continued receiving BKZ 320 mg sc Q8W for 40 additional weeks until OLE2 Week 48 in OLE2 Period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Bimzelx®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 320 mg at pre-specified time-points.

    Arm title
    		 OLE2 Period -Group B: BKZ 320 mg Q4W/Q8W
    Arm description
    		 Participants who completed the Week 144 visit and were participating in the SFU or had completed the SFU visit reinitiated their treatment in the OLE2 Period after having undergone Screening assessments during a 4-week OLE2 Screening Period. Participants with an IGA score greater than or equal to (>=) 3 at the Week 144/OLE2 Baseline Visit received BKZ 320 mg sc Q4W for the first 16 weeks, and then switched to BKZ 320 mg sc Q8W for 24 weeks until OLE2 Week 48 in OLE2 Period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    UCB4940
    Other name
    Bimzelx®
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 320 mg at pre-specified time-points.

    Number of subjects in period 4 [2]
    		OLE2 Period - Group A: BKZ 320 mg Q8W OLE2 Period - Group B: BKZ 320 mg Q8W OLE2 Period -Group B: BKZ 320 mg Q4W/Q8W
    Started
    9
    66
    59
    Completed
    6
    61
    52
    Not completed
    3
    5
    7
         Adverse event, non-fatal
    1
    2
    1
         Subject had threatening behavior to site staff
    -
    -
    1
         Lost to follow-up
    2
    2
    2
         Site's business is closing on 30 september 2022
    -
    1
    -
         Site closure
    -
    -
    3
    Notes
    [2] - 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: Participants who provided consent to continue in OLE2 Period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ITP: Bimekizumab (BKZ) 320 milligrams (mg) Q4W
    Reporting group description
    		 Participants randomized to this arm received BKZ 320 mg subcutaneously (sc) every 4 weeks (Q4W) for 16 weeks in the Initial Treatment Period (ITP). Placebo was administered at pre-specified time-points to maintain the blinding.

    Reporting group title
    ITP: Secukinumab 300 mg Q4W
    Reporting group description
    		 Participants received secukinumab 300 mg sc at Baseline and Weeks 1, 2, 3, and 4 followed by dosing Q4W until Week 16 in the Initial Treatment Period.

    Reporting group values
    		 ITP: Bimekizumab (BKZ) 320 milligrams (mg) Q4W ITP: Secukinumab 300 mg Q4W Total
    Number of subjects
    		 373 370 743
    Age Categorical
    Units: Participants
        <=18 years
    		 3 7 10
        Between 18 and 65 years
    		 332 324 656
        >=65 years
    		 38 39 77
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 45.9 ( 14.2 ) 44.0 ( 14.7 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 122 135 257
        Male
    		 251 235 486

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    ITP: Bimekizumab (BKZ) 320 milligrams (mg) Q4W
    Reporting group description
    		 Participants randomized to this arm received BKZ 320 mg subcutaneously (sc) every 4 weeks (Q4W) for 16 weeks in the Initial Treatment Period (ITP). Placebo was administered at pre-specified time-points to maintain the blinding.

    Reporting group title
    ITP: Secukinumab 300 mg Q4W
    Reporting group description
    		 Participants received secukinumab 300 mg sc at Baseline and Weeks 1, 2, 3, and 4 followed by dosing Q4W until Week 16 in the Initial Treatment Period.
    Reporting group title
    MTP: BKZ 320 mg Q4W/Q8W
    Reporting group description
    		 Participants randomized to this arm received BKZ 320 mg sc Q4W for 16 weeks in the Initial Treatment Period. At Week 16, participants were re-randomized to receive bimekizumab 320 mg sc Q8W until Week 48 in the Maintenance Treatment Period (MTP). Placebo was administered at pre-specified time-points to maintain the blinding.

    Reporting group title
    MTP: BKZ 320 mg Q4W/Q4W
    Reporting group description
    		 Participants randomized to this arm received BKZ 320 mg sc Q4W for 16 weeks in the Initial Treatment Period. At Week 16, participants continued to receive BKZ 320 mg sc every 4 Weeks (Q4W/Q4W) until Week 48 in the Maintenance Treatment Period.

    Reporting group title
    MTP: Secukinumab 300 mg Q4W/Q4W
    Reporting group description
    		 Participants in secukinumab arm continued to receive secukinumab 300 mg sc Q4W until Week 48 in the Maintenance Treatment Period.
    Reporting group title
    OLE Period: BKZ Week 0-48/BKZ Q8W 320 mg
    Reporting group description
    		 Participants randomized to this arm received BKZ 320 mg sc Q4W for the first 16 weeks and then re-randomized to receive BKZ 320 mg sc Q4W or Q8W until Week 48 of the double-blind Treatment Period. Based on the PASI90 response and the dose the participant was receiving at Week 48, participants were randomized to receive BKZ 320 mg sc Q8W until Week 136 in the Open-Label Extension (OLE) Period.

    Reporting group title
    OLE Period: BKZ Week 0-48/ BKZ Q4W 320 mg
    Reporting group description
    		 Participants randomized to this arm received BKZ 320 mg sc Q4W for the first 16 weeks and then re-randomized to receive BKZ 320 mg sc Q4W or Q8W until Week 48 of the double-blind Treatment Period. Based on the PASI90 response and the dose the participant was receiving at Week 48, participants were randomized to receive BKZ 320 mg sc Q4W starting in OLE Period. The participant’s dosing interval was changed from BKZ 320mg Q4W to BKZ 320mg Q8W at Week 64, or at the next scheduled clinic visit if the participant has already completed the Week 64 after protocol amendment 5.

    Reporting group title
    OLE Period: Secukinumab Week 0-48/ BKZ Q8W 320 mg
    Reporting group description
    		 Participants randomized to this arm received Secukinumab 300 mg sc Q4W until Week 48 of the double-blind Treatment Period. Based on the PASI90 response in double-blind Treatment Period, participants randomized to receive BKZ 320 mg sc Q8W until Week 136 of the OLE Period.

    Reporting group title
    OLE Period: Secukinumab Week 0-48/ BKZ Q4W 320 mg
    Reporting group description
    		 Participants randomized to this arm received Secukinumab 300 mg sc Q4W until Week 48 of the double-blind Treatment Period. Based on the PASI90 response in double-blind Treatment Period, participants randomized to receive BKZ 320 mg sc Q4W starting in OLE Period. The participant’s dosing interval was changed from BKZ 320mg Q4W to BKZ 320mg Q8W at Week 64, or at the next scheduled clinic visit if the participant has already completed the Week 64 after protocol amendment 5.
    Reporting group title
    OLE2 Period - Group A: BKZ 320 mg Q8W
    Reporting group description
    		 Participants who were still receiving treatment in the OLE Period and attended the Week 144 visit were directly rolled over to the OLE2 Period. In OLE2 Period, participants continued receiving BKZ 320 mg sc Q8W for 40 additional weeks until OLE2 Week 48.

    Reporting group title
    OLE2 Period - Group B: BKZ 320 mg Q8W
    Reporting group description
    		 Participants who completed the Week 144 and were participating in the Safety Follow-Up (SFU) or had completed the SFU visit reinitiated their treatment in the OLE2 Period after having undergone Screening assessments during a 4-week OLE2 Screening Period. Participants with an IGA score less than (<) 3 at the Week 144/OLE2 Baseline Visit continued receiving BKZ 320 mg sc Q8W for 40 additional weeks until OLE2 Week 48 in OLE2 Period.

    Reporting group title
    OLE2 Period -Group B: BKZ 320 mg Q4W/Q8W
    Reporting group description
    		 Participants who completed the Week 144 visit and were participating in the SFU or had completed the SFU visit reinitiated their treatment in the OLE2 Period after having undergone Screening assessments during a 4-week OLE2 Screening Period. Participants with an IGA score greater than or equal to (>=) 3 at the Week 144/OLE2 Baseline Visit received BKZ 320 mg sc Q4W for the first 16 weeks, and then switched to BKZ 320 mg sc Q8W for 24 weeks until OLE2 Week 48 in OLE2 Period.

    Subject analysis set title
    ITP: Bimekizumab (BKZ) 320 mg Q4W
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants randomized to this arm received BKZ 320 mg sc Q4W for 16 weeks in the Initial Treatment Period (ITP). Placebo was administered at pre-specified time-points to maintain the blinding.

    Subject analysis set title
    ITP: Secukinumab 300 mg Q4W
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received secukinumab 300 mg sc at Baseline and Weeks 1, 2, 3, and 4 followed by dosing Q4W until Week 16 in the Initial Treatment Period.

    Subject analysis set title
    ITP+MTP: BKZ Q4W/Q4W +BKZ Q4W/Q8W
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants randomized to this arm received BKZ 320 mg sc Q4W for 16 weeks in the ITP. At Week 16, participants either continued to receive BKZ 320 mg sc every 4 Weeks (Q4W/Q4W) or re-randomized to receive BKZ 320 mg sc Q8W until Week 48 in the MTP. Placebo was administered at pre-specified time-points to maintain the blinding.

    Subject analysis set title
    ITP+MTP: Secukinumab 300 mg Q4W/Q4W
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received secukinumab 300 mg sc at Baseline and Weeks 1, 2, 3, and 4 followed by dosing Q4W until Week 16 in the ITP. Participants continued to receive secukinumab 300 mg sc Q4W until Week 48 in the MTP.

    Subject analysis set title
    MTP: BKZ 320 mg Q4W/Q8W
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants randomized to this arm received BKZ 320 mg sc Q4W for 16 weeks in the Initial Treatment Period. At Week 16, participants were re-randomized to receive BKZ 320 mg sc Q8W until Week 48 in the Maintenance Treatment Period (MTP). Placebo was administered at pre-specified time-points to maintain the blinding.

    Subject analysis set title
    MTP: BKZ 320 mg Q4W/Q4W
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants randomized to this arm received BKZ 320 mg sc Q4W for 16 weeks in the Initial Treatment Period. At Week 16, participants continued to receive BKZ 320 mg sc every 4 Weeks (Q4W/Q4W) until Week 48 in the Maintenance Treatment Period.

    Subject analysis set title
    MTP: Secukinumab 300 mg Q4W/Q4W
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants in secukinumab arm continued to receive secukinumab 300 mg sc Q4W until Week 48 in the Maintenance Treatment Period.

    Subject analysis set title
    MTP: BKZ 320 mg Q8W (Week 16 to Week 48)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants who received at least one dose of BKZ 320 mg sc Q8W from Week 16 until Week 48.

    Subject analysis set title
    ITP+MTP: BKZ 320 mg Q4W (up to Week 48)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants who received at least one dose of BKZ 320 mg sc Q4W until Week 48.

    Subject analysis set title
    ITP+MTP: Secukinumab 300 mg Q4W (up to Week 48)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received secukinumab 300 mg sc at Baseline and Weeks 1, 2, 3, and 4 followed by dosing Q4W until Week 48.

    Subject analysis set title
    OLE Period: BKZ 320 mg Q8W (Week 48 to Week 144)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received BKZ 320 mg sc Q8W from Week 48 until Week 136 during OLE Period. For participants that received both BKZ 320 mg Q4W and Q8W, events are counted in the dose group most recently received prior to the date of the event or assessment.

    Subject analysis set title
    OLE Period: BKZ 320 mg Q4W (Week 48 to Week 144)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received BKZ 320 mg sc Q4W from Week 48 until Week 136 during OLE Period. The participant's dosing interval was changed from BKZ 320 mg Q4W to BKZ 320 mg Q8W at Week 64, or at the next scheduled clinic visit if the participant has already completed the Week 64.

    Subject analysis set title
    OLE2 Period - Group A: BKZ 320 mg Q8W
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants who were still receiving treatment in the OLE Period and attended the Week 144 visit were directly rolled over to the OLE2 Period. In OLE2 Period, participants continued receiving BKZ 320 mg sc Q8W for 40 additional weeks until OLE2 Week 48.

    Subject analysis set title
    OLE2 Period - Group B: BKZ 320 mg Q8W
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants who completed the Week 144 and were participating in the Safety Follow-Up (SFU) or had completed the SFU visit reinitiated their treatment in the OLE2 Period after having undergone Screening assessments during a 4-week OLE2 Screening Period. Participants with an IGA score less than (<) 3 at the Week 144/OLE2 Baseline Visit continued receiving BKZ 320 mg sc Q8W for 40 additional weeks until OLE2 Week 48 in OLE2 Period.

    Subject analysis set title
    OLE2 Period -Group B: BKZ 320 mg Q4W/Q8W
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants who completed the Week 144 visit and were participating in the SFU or had completed the SFU visit reinitiated their treatment in the OLE2 Period after having undergone Screening assessments during a 4-week OLE2 Screening Period. Participants with an IGA score greater than or equal to (>=) 3 at the Week 144/OLE2 Baseline Visit received BKZ 320 mg sc Q4W for the first 16 weeks, and then switched to BKZ 320 mg sc Q8W for 24 weeks until OLE2 Week 48 in OLE2 Period.

    Primary: Percentage of Participants with a Psoriasis Area and Severity Index 100 (PASI100) Response at Week 16

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    End point title
    		 Percentage of Participants with a Psoriasis Area and Severity Index 100 (PASI100) Response at Week 16
    End point description
    The PASI100 response assessments are based on 100% improvement in PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. The Randomized Set (RS) consisted of all randomized study participants.
    End point type
    Primary
    End point timeframe
    Week 16
    End point values
    		 ITP: Bimekizumab (BKZ) 320 mg Q4W ITP: Secukinumab 300 mg Q4W
    Number of subjects analysed
    373
    370
    Units: percentage of participants
        number (not applicable)
    61.7
    48.9
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Odds ratio calculated using stratified CMH test with region and prior biologic exposure as stratification variables.
    Comparison groups
    ITP: Bimekizumab (BKZ) 320 mg Q4W v ITP: Secukinumab 300 mg Q4W
    Number of subjects included in analysis
    743
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.714
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.271
         upper limit
    		 2.31
    Notes
    [1] - P-values for the comparison of treatment groups are based on the CMH test for the general association.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk Difference: BKZ-Secukinumab calculated using stratified Cochran-Mantel-Haenszel (CMH).
    Comparison groups
    ITP: Bimekizumab (BKZ) 320 mg Q4W v ITP: Secukinumab 300 mg Q4W
    Number of subjects included in analysis
    743
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    12.682
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.771
         upper limit
    		 19.592
    Notes
    [2] - The evaluation of noninferiority is tested at a 1-sided alpha level of 0.025 and based on a 1-sided 97.5% CI and a noninferiority margin of 10%.

    Secondary: Percentage of Participants with a PASI75 Response at Week 4

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    End point title
    		 Percentage of Participants with a PASI75 Response at Week 4
    End point description
    The PASI75 response assessments are based on at least 75% improvement in PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for redness, thickness, and scaling for each of the 4 body areas with score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of body areas and converting to 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. The Randomized Set (RS) consisted of all randomized study participants.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 ITP: Bimekizumab (BKZ) 320 mg Q4W ITP: Secukinumab 300 mg Q4W
    Number of subjects analysed
    373
    370
    Units: percentage of participants
        number (not applicable)
    71.0
    47.3
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Odds ratio calculated using stratified CMH test with region and prior biologic exposure as stratification variables.
    Comparison groups
    ITP: Bimekizumab (BKZ) 320 mg Q4W v ITP: Secukinumab 300 mg Q4W
    Number of subjects included in analysis
    743
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.817
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.068
         upper limit
    		 3.836
    Notes
    [3] - P-values for the comparison of treatment groups are based on the CMH test from the general association. P-values are not controlled for multiplicity and should only be considered descriptively.

    Secondary: Percentage of Participants with a PASI90 Response at Week 16

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    End point title
    		 Percentage of Participants with a PASI90 Response at Week 16
    End point description
    The PASI90 response assessments are based on at least 90% improvement in PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for redness, thickness, and scaling for each of the 4 body areas with score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI=average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. The Randomized Set (RS) consisted of all randomized study participants.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 ITP: Bimekizumab (BKZ) 320 mg Q4W ITP: Secukinumab 300 mg Q4W
    Number of subjects analysed
    373
    370
    Units: percentage of participants
        number (not applicable)
    85.5
    74.3
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a PASI100 Response at Week 48

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    End point title
    		 Percentage of Participants with a PASI100 Response at Week 48
    End point description
    PASI100 response assessments are based on 100% improvement in PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining percentage of skin covered with PSO for each of body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person’s affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. The RS consisted of all randomized study participants. The MS consisted of all study participants that received at least 1 dose of IMP at Week 16 or later in the Double-Blind Treatment Period (including the Week 16 dose).
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 ITP+MTP: BKZ Q4W/Q4W +BKZ Q4W/Q8W ITP+MTP: Secukinumab 300 mg Q4W/Q4W MTP: BKZ 320 mg Q4W/Q8W MTP: BKZ 320 mg Q4W/Q4W MTP: Secukinumab 300 mg Q4W/Q4W
    Number of subjects analysed
    373
    370
    215
    147
    354
    Units: percentage of participants
        number (not applicable)
    67.3
    46.2
    66.5
    73.5
    48.3
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Odds ratio calculated using stratified CMH test with region and prior biologic exposure as stratification variables.
    Comparison groups
    ITP+MTP: BKZ Q4W/Q4W +BKZ Q4W/Q8W v ITP+MTP: Secukinumab 300 mg Q4W/Q4W
    Number of subjects included in analysis
    743
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.835
         upper limit
    		 3.377
    Notes
    [4] - P-values for the comparison of treatment groups are based on the CMH test from the general association. P-values are not controlled for multiplicity and should only be considered descriptively.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Odds ratio calculated using stratified CMH test with region and prior biologic exposure as stratification variables.
    Comparison groups
    MTP: BKZ 320 mg Q4W/Q4W v MTP: Secukinumab 300 mg Q4W/Q4W
    Number of subjects included in analysis
    501
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [5]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.243
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.103
         upper limit
    		 5
    Notes
    [5] - P-values for the comparison of treatment groups are based on the CMH test from the general association.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Odds ratio calculated using stratified CMH test with region and prior biologic exposure as stratification variables.
    Comparison groups
    MTP: BKZ 320 mg Q4W/Q8W v MTP: Secukinumab 300 mg Q4W/Q4W
    Number of subjects included in analysis
    569
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [6]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.168
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.511
         upper limit
    		 3.11
    Notes
    [6] - P-values for the comparison of treatment groups are based on the CMH test from the general association.

    Secondary: Percentage of Participants with a Investigator´s Global Assessment (IGA) Response (0/1) at Week 16

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    End point title
    		 Percentage of Participants with a Investigator´s Global Assessment (IGA) Response (0/1) at Week 16
    End point description
    The IGA measures the overall psoriasis severity following a 5-point scale (0-4), where scale 0= clear, no signs of psoriasis; presence of post-inflammatory hyperpigmentation, scale 1= almost clear, no thickening; normal to pink coloration; no to minimal focal scaling, scale 2= mild thickening, pink to light red coloration and predominately fine scaling, 3= moderate, clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable to moderate thickening; moderate scaling and 4= severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. IGA response was defined as Clear (0) or Almost Clear (1) with at least a two-category improvement from Baseline at Week 16. The Randomized Set (RS) consisted of all randomized study participants.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 ITP: Bimekizumab (BKZ) 320 mg Q4W ITP: Secukinumab 300 mg Q4W
    Number of subjects analysed
    373
    370
    Units: percentage of participants
        number (not applicable)
    85.5
    78.6
    No statistical analyses for this end point

    Secondary: Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Investigational Medicinal Product (IMP) from Baseline up to Week 225

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    End point title
    		 Number of Treatment-emergent Adverse Events (TEAEs) Adjusted by Duration of Participant Exposure to Investigational Medicinal Product (IMP) from Baseline up to Week 225
    End point description
    The number of TEAEs adjusted by duration of exposure to study treatment was scaled such that provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used. The Safety Set (SS) consisted of all study participants that received at least 1 dose of IMP. The Open-Label Set (OLS) consisted of all study participants who received at least 1 dose of BKZ at Week 48 or later in the OLE Period (including the Week 48 dose). The Open-Label Set 2 (OLS2) consisted of all study participants who received at least 1 dose of BKZ at the Week 144/OLE2 Baseline Visit or later in the OLE2 Period (including the Week 144/OLE2 Baseline dose).
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 225
    End point values
    		 MTP: BKZ 320 mg Q8W (Week 16 to Week 48) ITP+MTP: BKZ 320 mg Q4W (up to Week 48) ITP+MTP: Secukinumab 300 mg Q4W (up to Week 48) OLE Period: BKZ 320 mg Q8W (Week 48 to Week 144) OLE Period: BKZ 320 mg Q4W (Week 48 to Week 144) OLE2 Period - Group A: BKZ 320 mg Q8W OLE2 Period - Group B: BKZ 320 mg Q8W OLE2 Period -Group B: BKZ 320 mg Q4W/Q8W
    Number of subjects analysed
    215
    373
    370
    626
    294
    9
    66
    59
    Units: no. of new events per 100 subject-years
        number (confidence interval 95%)
    250.13 (213.09 to 291.75)
    331.26 (293.40 to 372.66)
    234.88 (209.22 to 262.83)
    115.35 (105.27 to 126.14)
    165.22 (143.73 to 189.02)
    164.95 (66.32 to 339.86)
    74.25 (51.72 to 103.26)
    94.18 (65.97 to 130.39)
    No statistical analyses for this end point

    Secondary: Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to IMP from Baseline up to Week 225

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    End point title
    		 Number of Serious Adverse Events (SAEs) Adjusted by Duration of Participant Exposure to IMP from Baseline up to Week 225
    End point description
    The number of SAEs adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used. The SS consisted of all study participants that received at least 1 dose of IMP. The OLS consisted of all study participants who received at least 1 dose of BKZ at Week 48 or later in the OLE Period (including the Week 48 dose). The OLS2 consisted of all study participants who received at least 1 dose of BKZ at the Week 144/OLE2 Baseline Visit or later in the OLE2 Period (including the Week 144/OLE2 Baseline dose).
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 225
    End point values
    		 MTP: BKZ 320 mg Q8W (Week 16 to Week 48) ITP+MTP: BKZ 320 mg Q4W (up to Week 48) ITP+MTP: Secukinumab 300 mg Q4W (up to Week 48) OLE Period: BKZ 320 mg Q8W (Week 48 to Week 144) OLE Period: BKZ 320 mg Q4W (Week 48 to Week 144) OLE2 Period - Group A: BKZ 320 mg Q8W OLE2 Period - Group B: BKZ 320 mg Q8W OLE2 Period -Group B: BKZ 320 mg Q4W/Q8W
    Number of subjects analysed
    215
    373
    370
    626
    294
    9
    66
    59
    Units: no. of new events per 100 subject-years
        number (confidence interval 95%)
    6.94 (3.17 to 13.17)
    7.33 (4.10 to 12.09)
    6.75 (4.23 to 10.22)
    5.93 (4.48 to 7.70)
    4.34 (2.16 to 7.76)
    12.28 (0.31 to 68.43)
    1.38 (0.03 to 7.66)
    6.39 (1.74 to 16.37)
    No statistical analyses for this end point

    Secondary: Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to IMP from Baseline up to Week 225

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    End point title
    		 Number of TEAEs Leading to Withdrawal Adjusted by Duration of Participant Exposure to IMP from Baseline up to Week 225
    End point description
    The number of TEAEs leading to discontinuation adjusted by duration of exposure to study treatment was scaled such that it provided an incidence rate per 100 patient-years. If a participant had multiple events, the time of exposure was calculated to the first occurrence of the AE being considered. If a participant had no events, the total time at risk was used. The SS consisted of all study participants that received at least 1 dose of IMP. The OLS consisted of all study participants who received at least 1 dose of BKZ at Week 48 or later in the OLE Period (including the Week 48 dose). The OLS2 consisted of all study participants who received at least 1 dose of BKZ at the Week 144/OLE2 Baseline Visit or later in the OLE2 Period (including the Week 144/OLE2 Baseline dose).
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 225
    End point values
    		 MTP: BKZ 320 mg Q8W (Week 16 to Week 48) ITP+MTP: BKZ 320 mg Q4W (up to Week 48) ITP+MTP: Secukinumab 300 mg Q4W (up to Week 48) OLE Period: BKZ 320 mg Q8W (Week 48 to Week 144) OLE Period: BKZ 320 mg Q4W (Week 48 to Week 144) OLE2 Period - Group A: BKZ 320 mg Q8W OLE2 Period - Group B: BKZ 320 mg Q8W OLE2 Period -Group B: BKZ 320 mg Q4W/Q8W
    Number of subjects analysed
    215
    373
    370
    626
    294
    9
    66
    59
    Units: no. of new events per 100 subject-years
        number (confidence interval 95%)
    1.51 (0.18 to 5.45)
    5.85 (3.02 to 10.22)
    3.33 (1.66 to 5.96)
    2.56 (1.65 to 3.77)
    3.52 (1.61 to 6.69)
    11.33 (0.29 to 63.10)
    2.76 (0.33 to 9.99)
    0 (0 to 0)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Baseline up to 165 weeks for each study participant not entering the OLE2 Period and up to 225 weeks for participants entering OLE2 Period
    Adverse event reporting additional description
    TEAEs were defined as those AEs that have a start date on or following the first dose of study treatment through final dose of study treatment + 140 days (covering 20-week SFU period). For participants that switched from BKZ 320 mg Q4W to Q8W, events prior to switch are counted in Q4W group and events after switch are counted in Q8W group.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    MTP: BKZ 320 mg Q8W (Week 16 to Week 48)
    Reporting group description
    		 Participants who received at least one dose of BKZ 320 mg sc Q8W from Week 16 until Week 48.

    Reporting group title
    ITP: Secukinumab 300 mg Q4W (up to Week 16)
    Reporting group description
    		 Participants received secukinumab 300 mg sc at Baseline and Weeks 1, 2, 3, and 4 followed by dosing Q4W until Week 16 in the Initial Treatment Period.

    Reporting group title
    ITP: BKZ 320 mg Q4W (up to Week 16)
    Reporting group description
    		 Participants randomized to this arm received BKZ 320 mg sc Q4W for 16 weeks in the Initial Treatment Period (ITP). Placebo was administered at pre-specified time-points to maintain the blinding.

    Reporting group title
    OLE Period: BKZ 320 mg Q4W (Week 48 to Week 144)
    Reporting group description
    		 Participants received BKZ 320 mg sc Q4W from Week 48 until Week 136 during OLE Period. The participant's dosing interval was changed from BKZ 320 mg Q4W to BKZ 320 mg Q8W at Week 64, or at the next scheduled clinic visit if the participant has already completed the Week 64.

    Reporting group title
    OLE2 Period - Group A: BKZ 320 mg Q8W
    Reporting group description
    		 Participants who were still receiving treatment in the OLE Period and attended the Week 144 visit were directly rolled over to the OLE2 Period. In OLE2 Period, participants continued receiving BKZ 320 mg sc Q8W for 40 additional weeks until OLE2 Week 48. Due to small number of participants, each event met the 5% threshold frequency criteria.

    Reporting group title
    OLE2 Period - Group B: BKZ 320 mg Q8W
    Reporting group description
    		 Participants who completed the Week 144 and were participating in the Safety Follow-Up (SFU) or had completed the SFU visit reinitiated their treatment in the OLE2 Period after having undergone Screening assessments during a 4-week OLE2 Screening Period. Participants with an IGA score less than (<) 3 at the Week 144/OLE2 Baseline Visit continued receiving BKZ 320 mg sc Q8W for 40 additional weeks until OLE2 Week 48 in OLE2 Period.

    Reporting group title
    OLE Period: BKZ 320 mg Q8W (Week 48 to Week 144)
    Reporting group description
    		 Participants received BKZ 320 mg sc Q8W from Week 48 until Week 136 during OLE Period. For participants that received both BKZ 320 mg Q4W and Q8W, events are counted in the dose group most recently received prior to the date of the event or assessment.

    Reporting group title
    OLE2 Period -Group B: BKZ 320 mg Q4W/Q8W
    Reporting group description
    		 Participants who completed the Week 144 visit and were participating in the SFU or had completed the SFU visit reinitiated their treatment in the OLE2 Period after having undergone Screening assessments during a 4-week OLE2 Screening Period. Participants with an IGA score greater than or equal to (>=) 3 at the Week 144/OLE2 Baseline Visit received BKZ 320 mg sc Q4W for the first 16 weeks, and then switched to BKZ 320 mg sc Q8W for 24 weeks until OLE2 Week 48 in OLE2 Period.

    Reporting group title
    ITP+MTP: BKZ 320 mg Q4W (up to Week 48)
    Reporting group description
    		 Participants who received at least one dose of BKZ 320 mg sc Q4W until Week 48.

    Reporting group title
    ITP+MTP: Secukinumab 300 mg Q4W (up to Week 48)
    Reporting group description
    		 Participants received secukinumab 300 mg sc at Baseline and Weeks 1, 2, 3, and 4 followed by dosing Q4W until Week 48.

    Serious adverse events
    		 MTP: BKZ 320 mg Q8W (Week 16 to Week 48) ITP: Secukinumab 300 mg Q4W (up to Week 16) ITP: BKZ 320 mg Q4W (up to Week 16) OLE Period: BKZ 320 mg Q4W (Week 48 to Week 144) OLE2 Period - Group A: BKZ 320 mg Q8W OLE2 Period - Group B: BKZ 320 mg Q8W OLE Period: BKZ 320 mg Q8W (Week 48 to Week 144) OLE2 Period -Group B: BKZ 320 mg Q4W/Q8W ITP+MTP: BKZ 320 mg Q4W (up to Week 48) ITP+MTP: Secukinumab 300 mg Q4W (up to Week 48)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 215 (4.19%)
    6 / 370 (1.62%)
    10 / 373 (2.68%)
    11 / 294 (3.74%)
    1 / 9 (11.11%)
    1 / 66 (1.52%)
    56 / 626 (8.95%)
    4 / 59 (6.78%)
    15 / 373 (4.02%)
    22 / 370 (5.95%)
         number of deaths (all causes)
    1
    0
    0
    1
    0
    0
    3
    1
    0
    2
         number of deaths resulting from adverse events
    1
    0
    0
    1
    0
    0
    3
    1
    0
    2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant melanoma in situ
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    1 / 373 (0.27%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    2 / 626 (0.32%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angiofibroma
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer stage III
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hodgkin's disease nodular sclerosis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lentigo maligna
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    1 / 66 (1.52%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parathyroid tumour benign
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    1 / 9 (11.11%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    1 / 59 (1.69%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastatic neoplasm
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thromboangiitis obliterans
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Surgical and medical procedures
    Abortion induced
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy on oral contraceptive
         subjects affected / exposed
    0 / 215 (0.00%)
    1 / 370 (0.27%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy on contraceptive
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 215 (0.47%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Uterine polyp
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    1 / 373 (0.27%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    Endometriosis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    0 / 215 (0.00%)
    1 / 370 (0.27%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Asphyxia
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Aspiration
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pulmonary embolism
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    1 / 373 (0.27%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Road traffic accident
         subjects affected / exposed
    1 / 215 (0.47%)
    0 / 370 (0.00%)
    1 / 373 (0.27%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Laceration
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    1 / 373 (0.27%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    1 / 373 (0.27%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    1 / 373 (0.27%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax traumatic
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin abrasion
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary artery disease
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 215 (0.47%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    2 / 294 (0.68%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    2 / 370 (0.54%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    2 / 626 (0.32%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    0 / 215 (0.00%)
    1 / 370 (0.27%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    IIIrd nerve paralysis
         subjects affected / exposed
    1 / 215 (0.47%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Relapsing-remitting multiple sclerosis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    1 / 59 (1.69%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Otosclerosis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Inguinal hernia
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    1 / 373 (0.27%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    1 / 373 (0.27%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    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
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum oesophageal
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic fistula
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    1 / 59 (1.69%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic pain
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Psoriasis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    1 / 373 (0.27%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermal cyst
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eczema
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erythrodermic psoriasis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Ureterolithiasis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    2 / 626 (0.32%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstructive nephropathy
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Endocrine disorder
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 215 (0.00%)
    1 / 370 (0.27%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 215 (0.00%)
    1 / 370 (0.27%)
    1 / 373 (0.27%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    4 / 626 (0.64%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 4
    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
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chondropathy
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis of jaw
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    2 / 626 (0.32%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Atypical pneumonia
         subjects affected / exposed
    0 / 215 (0.00%)
    1 / 370 (0.27%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    1 / 373 (0.27%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Extradural abscess
         subjects affected / exposed
    1 / 215 (0.47%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritoneal abscess
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    2 / 215 (0.93%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 215 (0.47%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    1 / 215 (0.47%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    1 / 59 (1.69%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    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
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Latent tuberculosis
         subjects affected / exposed
    1 / 215 (0.47%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis externa
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative abscess
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Candida sepsis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    1 / 294 (0.34%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    2 / 626 (0.32%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal skin infection
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Corona virus infection
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    5 / 626 (0.80%)
    1 / 59 (1.69%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 5
    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 / 2
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 MTP: BKZ 320 mg Q8W (Week 16 to Week 48) ITP: Secukinumab 300 mg Q4W (up to Week 16) ITP: BKZ 320 mg Q4W (up to Week 16) OLE Period: BKZ 320 mg Q4W (Week 48 to Week 144) OLE2 Period - Group A: BKZ 320 mg Q8W OLE2 Period - Group B: BKZ 320 mg Q8W OLE Period: BKZ 320 mg Q8W (Week 48 to Week 144) OLE2 Period -Group B: BKZ 320 mg Q4W/Q8W ITP+MTP: BKZ 320 mg Q4W (up to Week 48) ITP+MTP: Secukinumab 300 mg Q4W (up to Week 48)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    87 / 215 (40.47%)
    88 / 370 (23.78%)
    107 / 373 (28.69%)
    103 / 294 (35.03%)
    7 / 9 (77.78%)
    18 / 66 (27.27%)
    233 / 626 (37.22%)
    19 / 59 (32.20%)
    140 / 373 (37.53%)
    166 / 370 (44.86%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 215 (0.47%)
    1 / 370 (0.27%)
    2 / 373 (0.54%)
    1 / 294 (0.34%)
    1 / 9 (11.11%)
    0 / 66 (0.00%)
    3 / 626 (0.48%)
    2 / 59 (3.39%)
    3 / 373 (0.80%)
    2 / 370 (0.54%)
         occurrences all number
    1
    5
    2
    2
    1
    0
    4
    2
    3
    12
    Investigations
    White blood cell count increased
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    1 / 9 (11.11%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Psychiatric evaluation abnormal
         subjects affected / exposed
    1 / 215 (0.47%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    1 / 9 (11.11%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    1
    0
    0
    0
    Blood pressure increased
         subjects affected / exposed
    1 / 215 (0.47%)
    1 / 370 (0.27%)
    5 / 373 (1.34%)
    2 / 294 (0.68%)
    1 / 9 (11.11%)
    1 / 66 (1.52%)
    11 / 626 (1.76%)
    0 / 59 (0.00%)
    7 / 373 (1.88%)
    3 / 370 (0.81%)
         occurrences all number
    1
    1
    5
    2
    1
    1
    12
    0
    8
    3
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 215 (0.00%)
    1 / 370 (0.27%)
    2 / 373 (0.54%)
    0 / 294 (0.00%)
    1 / 9 (11.11%)
    1 / 66 (1.52%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    3 / 373 (0.80%)
    2 / 370 (0.54%)
         occurrences all number
    0
    1
    2
    0
    1
    1
    1
    0
    3
    2
    Fall
         subjects affected / exposed
    0 / 215 (0.00%)
    1 / 370 (0.27%)
    3 / 373 (0.80%)
    0 / 294 (0.00%)
    1 / 9 (11.11%)
    1 / 66 (1.52%)
    4 / 626 (0.64%)
    2 / 59 (3.39%)
    3 / 373 (0.80%)
    1 / 370 (0.27%)
         occurrences all number
    0
    1
    3
    0
    1
    1
    4
    2
    3
    1
    Nervous system disorders
    Paraesthesia
         subjects affected / exposed
    1 / 215 (0.47%)
    1 / 370 (0.27%)
    1 / 373 (0.27%)
    1 / 294 (0.34%)
    1 / 9 (11.11%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    1 / 373 (0.27%)
    1 / 370 (0.27%)
         occurrences all number
    1
    1
    1
    2
    1
    0
    0
    0
    1
    1
    Blood and lymphatic system disorders
    Macrocytosis
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    1 / 9 (11.11%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Polycythaemia
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    1 / 9 (11.11%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Malaise
         subjects affected / exposed
    0 / 215 (0.00%)
    1 / 370 (0.27%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    1 / 9 (11.11%)
    0 / 66 (0.00%)
    0 / 626 (0.00%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    Prostatomegaly
         subjects affected / exposed
    0 / 215 (0.00%)
    1 / 370 (0.27%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    1 / 9 (11.11%)
    0 / 66 (0.00%)
    1 / 626 (0.16%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    1 / 370 (0.27%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    1
    0
    0
    1
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    1 / 9 (11.11%)
    0 / 66 (0.00%)
    2 / 626 (0.32%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    2
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 215 (0.47%)
    1 / 370 (0.27%)
    0 / 373 (0.00%)
    0 / 294 (0.00%)
    1 / 9 (11.11%)
    0 / 66 (0.00%)
    3 / 626 (0.48%)
    0 / 59 (0.00%)
    0 / 373 (0.00%)
    2 / 370 (0.54%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    3
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Intertrigo
         subjects affected / exposed
    1 / 215 (0.47%)
    2 / 370 (0.54%)
    1 / 373 (0.27%)
    1 / 294 (0.34%)
    1 / 9 (11.11%)
    1 / 66 (1.52%)
    8 / 626 (1.28%)
    0 / 59 (0.00%)
    2 / 373 (0.54%)
    3 / 370 (0.81%)
         occurrences all number
    1
    2
    1
    1
    1
    1
    9
    0
    3
    4
    Psoriasis
         subjects affected / exposed
    1 / 215 (0.47%)
    2 / 370 (0.54%)
    4 / 373 (1.07%)
    5 / 294 (1.70%)
    0 / 9 (0.00%)
    1 / 66 (1.52%)
    38 / 626 (6.07%)
    1 / 59 (1.69%)
    5 / 373 (1.34%)
    16 / 370 (4.32%)
         occurrences all number
    1
    3
    4
    7
    0
    2
    40
    1
    6
    17
    Infections and infestations
    Corona virus infection
         subjects affected / exposed
    0 / 215 (0.00%)
    0 / 370 (0.00%)
    0 / 373 (0.00%)
    9 / 294 (3.06%)
    2 / 9 (22.22%)
    7 / 66 (10.61%)
    49 / 626 (7.83%)
    10 / 59 (16.95%)
    0 / 373 (0.00%)
    0 / 370 (0.00%)
         occurrences all number
    0
    0
    0
    9
    2
    7
    50
    10
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    33 / 215 (15.35%)
    54 / 370 (14.59%)
    47 / 373 (12.60%)
    34 / 294 (11.56%)
    0 / 9 (0.00%)
    3 / 66 (4.55%)
    62 / 626 (9.90%)
    1 / 59 (1.69%)
    62 / 373 (16.62%)
    102 / 370 (27.57%)
         occurrences all number
    40
    61
    54
    41
    0
    3
    85
    1
    76
    141
    Oral candidiasis
         subjects affected / exposed
    36 / 215 (16.74%)
    4 / 370 (1.08%)
    39 / 373 (10.46%)
    39 / 294 (13.27%)
    0 / 9 (0.00%)
    4 / 66 (6.06%)
    53 / 626 (8.47%)
    5 / 59 (8.47%)
    50 / 373 (13.40%)
    11 / 370 (2.97%)
         occurrences all number
    47
    4
    41
    51
    0
    4
    68
    7
    64
    16
    Upper respiratory tract infection
         subjects affected / exposed
    21 / 215 (9.77%)
    17 / 370 (4.59%)
    16 / 373 (4.29%)
    13 / 294 (4.42%)
    0 / 9 (0.00%)
    0 / 66 (0.00%)
    35 / 626 (5.59%)
    2 / 59 (3.39%)
    23 / 373 (6.17%)
    36 / 370 (9.73%)
         occurrences all number
    25
    17
    16
    13
    0
    0
    46
    2
    26
    39
    Urinary tract infection
         subjects affected / exposed
    10 / 215 (4.65%)
    7 / 370 (1.89%)
    6 / 373 (1.61%)
    19 / 294 (6.46%)
    1 / 9 (11.11%)
    1 / 66 (1.52%)
    30 / 626 (4.79%)
    0 / 59 (0.00%)
    15 / 373 (4.02%)
    22 / 370 (5.95%)
         occurrences all number
    14
    8
    7
    25
    1
    1
    40
    0
    19
    30

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Oct 2018
    Protocol Amendment 1 (dated 17 Oct 2018) was implemented to incorporate the following key changes: • Incorporated a rerandomization at Week 16 for study participants in the bimekizumab 320 mg treatment arm (study participants in the bimekizumab 320 mg treatment arm were rerandomized 1:2 to receive bimekizumab 320 mg Q4W or bimekizumab 320 mg Q8W). This change was implemented to assess the 2 bimekizumab maintenance regimens used in pivotal Phase 3 PSO studies relative to the active comparator. • Added the number of study participants included in the summary of the completed study UP0042. • Clarified the scalp-specific IGA and palmoplantar Investigator’s Global Assessment (pp-IGA) efficacy response criteria. • Moved the Patient Health Questionnaire-9 (PHQ-9) variable from an “other” safety variable to an “other” efficacy variable. • Added percent of study participants achieving at least a 75%, 90%, or 100% reduction from Baseline in the Modified Nail Psoriasis Severity Index (mNAPSI) score (mNAPSI75/90/100) for study participants with nail PSO at Baseline as an “other” efficacy variable. • Clarified that all study assessments should be performed prior to administration of IMP. • Clarified the study visit windows. • Clarified that the Patient’s Global Assessment of Disease Activity (PGADA) should be performed on all study participants at Baseline. • Defined mental healthcare professional. • Clarified the assessment and management of tuberculosis (TB) wording. • Clarified the drug accountability wording. • Revised the systemic retinoid washout period.
    17 Oct 2018
    Continuation of Protocol Amendment 1: • Clarified that the same assessor should evaluate the study participant at each assessment. • Removed the requirement for a rheumatologist evaluation for study participants with a Psoriatic Arthritis Screening and Evaluation (PASE) ≥47. • Clarified the IMP restart/rechallenge requirements in case of potential drug-induced liver injury (PDILI). • Added the definition of the Enrolled Set (ES) and Maintenance Set (MS). • Revised the statistical analysis based on the addition of rerandomization at Week 16. Minor spelling, editorial, and formatting changes were also made, and the List of Abbreviations was updated.
    06 May 2019
    Protocol Amendment 2 (dated 06 May 2019) was implemented to incorporate the following key changes: • Extended the study duration for an additional 96 weeks in an OLE Period. Changes included addition of a new schedule of assessments for the additional 96 weeks, additional other objectives and endpoints, and updates to Section 8 (Study procedures by visit). • Added planned rerandomization by treatment regimens and PASI response at Week 48 in the OLE Period. • Clarified secondary efficacy variable for IGA response at Week 16, and added other efficacy variables for the product of Investigator’s Global Assessment and body surface area (IGA×BSA) and PASE score suggestive of PsA. • Modified the text in Section 7 of the Protocol to include guidance for allowing study participants the option to self-inject IMP at home after Week 48. • Updated Section 12.2.1 of the Protocol (Evaluation of PDILI) for improved clarity and consistency with other Phase 3 studies of bimekizumab in study participants with PSO. • Added statistical analyses for the OLE Period. • Minor spelling, editorial, and formatting changes were made throughout the document.
    23 May 2019
    Protocol Amendment 3 (dated 23 May 2019) was implemented to incorporate the following key changes: • Moved study participant self-injection training into the start of the OLE Period at Week 48. • Added the description of the PGADA, which was inadvertently deleted in global Protocol Amendment 2, back into Section 9 of the Protocol. • Updated the name and contact information of the Clinical Trial Biostatistician. • Minor spelling, editorial, and formatting changes were made throughout the document.
    09 Jun 2020
    Protocol Amendment 5 (dated 09 Jun 2020) was implemented to incorporate the following key changes: • Changed the dosing regimen at Week 64 (or at the next scheduled clinic visit after implementation of Protocol Amendment 5 if the study participant already completed the Week 64 Visit) from bimekizumab 320 mg Q4W to bimekizumab 320 Q8W. This was based on pooled data from the Phase 3 studies (PS0008, PS0009, and PS0013), which demonstrated that during the Maintenance Treatment Period bimekizumab 320 mg Q8W provided essentially the same efficacy as bimekizumab 320 mg Q4W. • Corrected the visit window for the Week 24 visit from 7 days to 3 days. • Added a provision for collecting a concurrent sample for central laboratory testing if laboratory tests were performed locally. • Minor corrections, including typographical and grammatical errors, were made throughout the document.

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

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