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    Clinical Trial Results:
    A 52-Week, Phase 3, Randomized, Active Comparator and Placebo-Controlled, Parallel Design Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous Tildrakizumab (SCH 900222 / MK-3222), Followed by an Optional Long Term Safety Extension Study, in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Protocol No. MK-3222-011)

    Summary
    EudraCT number
    		 2012-001377-88
    Trial protocol
    		 DE   HU   AT   BE   CZ   IT   NL   DK  
    Global end of trial date
    26 Oct 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Jun 2023
    First version publication date
    30 Jun 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MK-3222-011
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01729754
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Sun Pharmaceutical Industries Limited
    Sponsor organisation address
    Sun House, 201 B/1, Western Express Highway, Goregaon (E), Mumbai, India, 400063
    Public contact
    Head-Clinical Development, Sun Pharmaceutical Industries Limited, Clinical.Trial@sunpharma.com
    Scientific contact
    Head-Clinical Development, Sun Pharmaceutical Industries Limited, Clinical.Trial@sunpharma.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
    28 Sep 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Sep 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Oct 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary Efficacy Objective: To assess the efficacy of tildrakizumab (SCH 900222/MK-3222), hereafter referred to as tildrakizumab (MK-3222), compared to placebo in the treatment of moderate-to-severe chronic plaque psoriasis as measured by the proportion of subjects with at least 75% improvement in the Psoriasis Area and Severity Index from baseline (PASI 75 response) and the proportion of subjects with a Physician’s Global Assessment (PGA) score of “clear” or “minimal” with at least a 2 grade reduction from baseline at Week 12. Primary Safety/Tolerability Objective: To assess the safety/tolerability of tildrakizumab (MK-3222) in subjects with moderate-to-severe chronic plaque psoriasis at Week 12.
    Protection of trial subjects
    The following measures are taken within the study for the protection of the trial subjects: -The investigator or sub-investigator to stop treatment in any case in which emerging effects are of unacceptable risk to the individual subject. -Subjects were free to withdraw his/her consent at any time without giving or stating any reason -All subjects screened for presence of latent or untreated TB infections, HIV, hepatitis B surface antigen, hepatitis C virus, chronic disease, organ dysfunction, use of prohibited medications and presence of any other such conditions to ensure to minimize the potential risk to study subjects prior to enrollment -Every subject will be monitored for the occurrence of SAEs immediately after the subject has signed informed consent form -Each subject will be followed up for adverse events for 20 weeks after the last visit in the treatment period. Protocol was developed in collaboration with a Scientific Advisory Committee (SAC). The SAC comprised of both Sponsor and non-Sponsor scientific experts who provided input with respect to trial design, interpretation of trial results and subsequent peer reviewed scientific publications; all subjects signed ICF and study procedures were initiated after voluntary written ICF was obtained; study protocol and essential documents were approved by ECs and RAs; an external DMC made recommendations to the Sponsor regarding steps to ensure both subject safety and the continued ethical integrity of the trial safety, DMC also considered the overall risk and benefit to trial participants and recommend to the Sponsor if the trial should continue in accordance with the protocol; An Executive Oversight Committee (EOC) comprising of members of Sponsor Senior Management received and decide upon any recommendations made by the external DMC regarding the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Dec 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 4 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 7
    Country: Number of subjects enrolled
    Poland: 97
    Country: Number of subjects enrolled
    Austria: 13
    Country: Number of subjects enrolled
    Belgium: 36
    Country: Number of subjects enrolled
    Czech Republic: 5
    Country: Number of subjects enrolled
    Denmark: 11
    Country: Number of subjects enrolled
    France: 43
    Country: Number of subjects enrolled
    Germany: 401
    Country: Number of subjects enrolled
    Hungary: 27
    Country: Number of subjects enrolled
    Italy: 50
    Country: Number of subjects enrolled
    Israel: 4
    Country: Number of subjects enrolled
    Canada: 94
    Country: Number of subjects enrolled
    United States: 302
    Worldwide total number of subjects
    1090
    EEA total number of subjects
    690
    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)
    993
    From 65 to 84 years
    97
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 1372 subjects were screened for the study, of which 282 subjects were not randomized into the study.

    Period 1
    Period 1 title
    Base Study - Part 1 (Day 1 to Week 12)
    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
    		 Placebo
    Arm description
    		 Tildrakizumab placebo SC at Weeks 0 and 4 and etanercept placebo SC twice weekly
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Matching placebo to tildrakizumab/etanercept administered SC

    Arm title
    		 Tildrakizumab 100 mg
    Arm description
    		 Tildrakizumab 100 mg SC at Weeks 0 and 4 and etanercept placebo SC twice weekly
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 100 mg administered SC.

    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Arm title
    		 Tildrakizumab 200 mg
    Arm description
    		 Tildrakizumab 200 mg SC at Weeks 0 and 4 and etanercept placebo SC twice weekly
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 200 mg administered SC.

    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Arm title
    		 Etanercept 50 mg
    Arm description
    		 Etanercept 50 mg SC twice weekly and tildrakizumab placebo SC at Weeks 0 and 4
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Etanercept
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Etanercept 50 mg administered SC

    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Number of subjects in period 1
    		Placebo Tildrakizumab 100 mg Tildrakizumab 200 mg Etanercept 50 mg
    Started
    156
    307
    314
    313
    Completed
    142
    295
    300
    289
    Not completed
    14
    12
    14
    24
         Consent withdrawn by subject
    5
    7
    5
    6
         Physician decision
    -
    -
    -
    4
         Non-Compliance with Study Drug
    -
    -
    1
    -
         Adverse event, non-fatal
    2
    1
    2
    5
         Progressive Disease
    -
    -
    -
    1
         Pregnancy
    -
    1
    -
    1
         Protocol Violation
    1
    1
    2
    -
         Other Protocol Specified Criteria
    1
    -
    2
    4
         Lost to follow-up
    3
    2
    1
    3
         Lack of efficacy
    2
    -
    1
    -
    Period 2
    Period 2 title
    Base period- Part 2 (Week 12 to Week 28)
    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
    No

    Arm title
    		 Placebo (Part 1) to Tildrakizumab 100 mg (Part 2)
    Arm description
    		 Tildrakizumab 100 mg SC at Weeks 12, and 16 and etanercept placebo SC once weekly. Treatment group included Part 1 placebo subjects re-randomized to tildrakizumab 100 mg at Week 12.
    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 100 mg administered SC.

    Arm title
    		 Placebo (Part 1) to Tildrakizumab 200 mg (Part 2)
    Arm description
    		 Tildrakizumab 200 mg SC at Weeks 12 and 16 and etanercept placebo SC once weekly Treatment group included Part 1 placebo subjects re-randomized to tildrakizumab 200 mg at Week 12
    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 200 mg administered SC.

    Arm title
    		 Tildrakizumab 100 mg (Part 1 and 2)
    Arm description
    		 Tildrakizumab 100 mg SC at Week 16, tildrakizumab placebo SC at Week 12, and etanercept placebo SC once weekly Treatment group included Part 1 tildrakizumab 100 mg treated subjects who continued on the same dose (tildrakizumab 100 mg) in Part 2.
    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 100 mg administered SC.

    Arm title
    		 Tildrakizumab 200 mg (Part 1 and 2)
    Arm description
    		 Tildrakizumab 200 mg SC at Week 16, tildrakizumab placebo SC at Week 12, and etanercept placebo SC once weekly. Treatment group included Part 1 tildrakizumab 200 mg treated subjects who continued on the same dose (tildrakizumab 200 mg) in Part 2.
    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 200 mg administered SC.

    Arm title
    		 Etanercept 50 mg (Part 1 and 2)
    Arm description
    		 Etanercept 50 mg SC once weekly and tildrakizumab placebo at Week 12 and Week 16. Treatment group included Part 1 etanercept subjects who continued on the same dose (etanercept 50 mg) in Part 2.
    Arm type
    		 Active comparator

    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Investigational medicinal product name
    Etanercept
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Etanercept 50 mg administered SC

    Number of subjects in period 2
    		Placebo (Part 1) to Tildrakizumab 100 mg (Part 2) Placebo (Part 1) to Tildrakizumab 200 mg (Part 2) Tildrakizumab 100 mg (Part 1 and 2) Tildrakizumab 200 mg (Part 1 and 2) Etanercept 50 mg (Part 1 and 2)
    Started
    70
    72
    294
    300
    289
    Completed
    66
    69
    289
    294
    277
    Not completed
    4
    3
    5
    6
    12
         Consent withdrawn by subject
    1
    1
    2
    3
    4
         Non-Compliance with Study Drug
    -
    -
    -
    -
    1
         Adverse event, non-fatal
    1
    -
    -
    2
    2
         Pregnancy
    -
    -
    1
    -
    1
         Other Protocol Specified Criteria
    -
    1
    -
    1
    -
         Lost to follow-up
    -
    1
    2
    -
    2
         Lack of efficacy
    2
    -
    -
    -
    2
    Period 3
    Period 3 title
    Base period- Part 3 (Week 28 to Week 52)
    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
    No

    Arm title
    		 Placebo (Part 1)/Tildrakizumab 100 mg (Parts 2 & 3)
    Arm description
    		 Tildrakizumab 100 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48. Treatment group included: Part 1 placebo subjects re-randomized to the tildrakizumab 100 mg in Part 2 who continued on the same dose (tildrakizumab 100 mg) in Part 3.
    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 100 mg administered SC.

    Arm title
    		 Tildrakizumab 100 mg (Part 1,2 and 3)
    Arm description
    		 Tildrakizumab 100 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48 Treatment group included: subjects originally randomized to tildrakizumab 100 mg in Part 1 who were responders or partial responders at Week 28 who continued on the same dose in Part 3.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 100 mg administered SC.

    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Arm title
    		 Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3)
    Arm description
    		 Tildrakizumab 200 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48 Treatment group included: subjects originally randomized to tildrakizumab 100 mg in Part 1 who were partial responders at Week 28 and were re-randomized at Week 28 to tildrakizumab 200 mg for Part 3.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 200 mg administered SC.

    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Arm title
    		 Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)
    Arm description
    		 Tildrakizumab 200 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48 Treatment group included: Part 1 placebo subjects re-randomized to the tildrakizumab 200 mg in Part 2 who continued on the same dose (tildrakizumab 200 mg) in Part 3.
    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 200 mg administered SC.

    Arm title
    		 Tildrakizumab 200 mg (Parts 1 & 2)/ 100 mg (Part 3)
    Arm description
    		 Tildrakizumab 100 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48 Treatment group included: subjects originally randomized to tildrakizumab 200 mg in Part 1 who were responders at Week 28 and were re-randomized at Week 28 to tildrakizumab 100 mg for Part 3.
    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 100 mg administered SC.

    Arm title
    		 Tildrakizumab 200 mg (Parts 1, 2, & 3)
    Arm description
    		 Tildrakizumab 200 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48. Treatment group included: subjects originally randomized to tildrakizumab 200 mg in Part 1 who were responders or partial responders at Week 28 who continued on the same dose in Part 3
    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 200 mg administered SC.

    Arm title
    		 Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)
    Arm description
    		 Tildrakizumab 200 mg SC at Weeks 32, 36, and 48 and tildrakizumab placebo SC at Weeks 28, 40, and 52. Treatment group included: subjects originally randomized to etanercept in Part 1 who were non-responders or partial responders at Week 28 and were assigned to tildrakizumab 200 mg in Part 3.
    Arm type
    		 Active comparator

    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
    Matching placebo to tildrakizumab/etanercept administered SC

    Investigational medicinal product name
    Tildrakizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Tildrakizumab 200 mg administered SC.

    Investigational medicinal product name
    Etanercept
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Etanercept 50 mg administered SC

    Number of subjects in period 3
    		Placebo (Part 1)/Tildrakizumab 100 mg (Parts 2 & 3) Tildrakizumab 100 mg (Part 1,2 and 3) Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3) Tildrakizumab 200 mg (Parts 1 & 2)/ 100 mg (Part 3) Tildrakizumab 200 mg (Parts 1, 2, & 3) Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)
    Started
    66
    237
    21
    69
    110
    170
    121
    Completed
    65
    224
    17
    66
    105
    165
    114
    Not completed
    1
    13
    4
    3
    5
    5
    7
         Adverse event, serious fatal
    -
    2
    -
    -
    -
    -
    -
         Consent withdrawn by subject
    -
    1
    2
    2
    1
    4
    -
         Physician decision
    -
    -
    -
    -
    1
    -
    -
         Adverse event, non-fatal
    -
    5
    -
    -
    1
    -
    3
         Other Protocol Specified Criteria
    -
    2
    -
    1
    -
    -
    -
         Lost to follow-up
    1
    3
    -
    -
    2
    1
    -
         Lack of efficacy
    -
    -
    2
    -
    -
    -
    4

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Tildrakizumab placebo SC at Weeks 0 and 4 and etanercept placebo SC twice weekly

    Reporting group title
    Tildrakizumab 100 mg
    Reporting group description
    		 Tildrakizumab 100 mg SC at Weeks 0 and 4 and etanercept placebo SC twice weekly

    Reporting group title
    Tildrakizumab 200 mg
    Reporting group description
    		 Tildrakizumab 200 mg SC at Weeks 0 and 4 and etanercept placebo SC twice weekly

    Reporting group title
    Etanercept 50 mg
    Reporting group description
    		 Etanercept 50 mg SC twice weekly and tildrakizumab placebo SC at Weeks 0 and 4

    Reporting group values
    		 Placebo Tildrakizumab 100 mg Tildrakizumab 200 mg Etanercept 50 mg Total
    Number of subjects
    		 156 307 314 313 1090
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 142 280 289 282 993
        From 65-84 years
    		 14 27 25 31 97
    Gender categorical
    Units: Subjects
        Female
    		 44 87 89 91 311
        Male
    		 112 220 225 222 779

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Tildrakizumab placebo SC at Weeks 0 and 4 and etanercept placebo SC twice weekly

    Reporting group title
    Tildrakizumab 100 mg
    Reporting group description
    		 Tildrakizumab 100 mg SC at Weeks 0 and 4 and etanercept placebo SC twice weekly

    Reporting group title
    Tildrakizumab 200 mg
    Reporting group description
    		 Tildrakizumab 200 mg SC at Weeks 0 and 4 and etanercept placebo SC twice weekly

    Reporting group title
    Etanercept 50 mg
    Reporting group description
    		 Etanercept 50 mg SC twice weekly and tildrakizumab placebo SC at Weeks 0 and 4
    Reporting group title
    Placebo (Part 1) to Tildrakizumab 100 mg (Part 2)
    Reporting group description
    		 Tildrakizumab 100 mg SC at Weeks 12, and 16 and etanercept placebo SC once weekly. Treatment group included Part 1 placebo subjects re-randomized to tildrakizumab 100 mg at Week 12.

    Reporting group title
    Placebo (Part 1) to Tildrakizumab 200 mg (Part 2)
    Reporting group description
    		 Tildrakizumab 200 mg SC at Weeks 12 and 16 and etanercept placebo SC once weekly Treatment group included Part 1 placebo subjects re-randomized to tildrakizumab 200 mg at Week 12

    Reporting group title
    Tildrakizumab 100 mg (Part 1 and 2)
    Reporting group description
    		 Tildrakizumab 100 mg SC at Week 16, tildrakizumab placebo SC at Week 12, and etanercept placebo SC once weekly Treatment group included Part 1 tildrakizumab 100 mg treated subjects who continued on the same dose (tildrakizumab 100 mg) in Part 2.

    Reporting group title
    Tildrakizumab 200 mg (Part 1 and 2)
    Reporting group description
    		 Tildrakizumab 200 mg SC at Week 16, tildrakizumab placebo SC at Week 12, and etanercept placebo SC once weekly. Treatment group included Part 1 tildrakizumab 200 mg treated subjects who continued on the same dose (tildrakizumab 200 mg) in Part 2.

    Reporting group title
    Etanercept 50 mg (Part 1 and 2)
    Reporting group description
    		 Etanercept 50 mg SC once weekly and tildrakizumab placebo at Week 12 and Week 16. Treatment group included Part 1 etanercept subjects who continued on the same dose (etanercept 50 mg) in Part 2.
    Reporting group title
    Placebo (Part 1)/Tildrakizumab 100 mg (Parts 2 & 3)
    Reporting group description
    		 Tildrakizumab 100 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48. Treatment group included: Part 1 placebo subjects re-randomized to the tildrakizumab 100 mg in Part 2 who continued on the same dose (tildrakizumab 100 mg) in Part 3.

    Reporting group title
    Tildrakizumab 100 mg (Part 1,2 and 3)
    Reporting group description
    		 Tildrakizumab 100 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48 Treatment group included: subjects originally randomized to tildrakizumab 100 mg in Part 1 who were responders or partial responders at Week 28 who continued on the same dose in Part 3.

    Reporting group title
    Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3)
    Reporting group description
    		 Tildrakizumab 200 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48 Treatment group included: subjects originally randomized to tildrakizumab 100 mg in Part 1 who were partial responders at Week 28 and were re-randomized at Week 28 to tildrakizumab 200 mg for Part 3.

    Reporting group title
    Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)
    Reporting group description
    		 Tildrakizumab 200 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48 Treatment group included: Part 1 placebo subjects re-randomized to the tildrakizumab 200 mg in Part 2 who continued on the same dose (tildrakizumab 200 mg) in Part 3.

    Reporting group title
    Tildrakizumab 200 mg (Parts 1 & 2)/ 100 mg (Part 3)
    Reporting group description
    		 Tildrakizumab 100 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48 Treatment group included: subjects originally randomized to tildrakizumab 200 mg in Part 1 who were responders at Week 28 and were re-randomized at Week 28 to tildrakizumab 100 mg for Part 3.

    Reporting group title
    Tildrakizumab 200 mg (Parts 1, 2, & 3)
    Reporting group description
    		 Tildrakizumab 200 mg SC at Weeks 28, 40, and 52 and tildrakizumab placebo SC at Weeks 32, 36, and 48. Treatment group included: subjects originally randomized to tildrakizumab 200 mg in Part 1 who were responders or partial responders at Week 28 who continued on the same dose in Part 3

    Reporting group title
    Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)
    Reporting group description
    		 Tildrakizumab 200 mg SC at Weeks 32, 36, and 48 and tildrakizumab placebo SC at Weeks 28, 40, and 52. Treatment group included: subjects originally randomized to etanercept in Part 1 who were non-responders or partial responders at Week 28 and were assigned to tildrakizumab 200 mg in Part 3.

    Primary: Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12

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    End point title
    		 Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12
    End point description
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Placebo Tildrakizumab 100 mg Tildrakizumab 200 mg Etanercept 50 mg
    Number of subjects analysed
    156
    307
    314
    313
    Units: Percentage of participants
        number (not applicable)
    5.8
    61.2
    65.6
    48.2
    Statistical analysis title
    		 CMH Analysis of PASI 75 at Week 12
    Comparison groups
    Tildrakizumab 200 mg v Placebo
    Number of subjects included in analysis
    470
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Primary: Percentage of Participants with a Physician's Global Assessment (PGA) Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 12

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    End point title
    		 Percentage of Participants with a Physician's Global Assessment (PGA) Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 12
    End point description
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Placebo Tildrakizumab 100 mg Tildrakizumab 200 mg Etanercept 50 mg
    Number of subjects analysed
    156
    307
    314
    313
    Units: Percentage of participants
        number (not applicable)
    4.5
    54.7
    59.2
    47.6
    Statistical analysis title
    		 CMH Analysis of PGA score at Week 12
    Comparison groups
    Placebo v Tildrakizumab 200 mg
    Number of subjects included in analysis
    470
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants Achieving a PASI-75 Response at Week 28

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    End point title
    		 Percentage of Participants Achieving a PASI-75 Response at Week 28
    End point description
    End point type
    Secondary
    End point timeframe
    Week 28
    End point values
    		 Tildrakizumab 100 mg (Part 1 and 2) Tildrakizumab 200 mg (Part 1 and 2) Etanercept 50 mg (Part 1 and 2)
    Number of subjects analysed
    294
    299
    289
    Units: Percentage of Participant
        number (not applicable)
    73.5
    72.6
    53.6
    Statistical analysis title
    		 CMH Analysis of PASI 75 at Week 28
    Comparison groups
    Tildrakizumab 100 mg (Part 1 and 2) v Etanercept 50 mg (Part 1 and 2)
    Number of subjects included in analysis
    583
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    		 CMH Analysis of PASI 75 at Week 28
    Comparison groups
    Tildrakizumab 200 mg (Part 1 and 2) v Etanercept 50 mg (Part 1 and 2)
    Number of subjects included in analysis
    588
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Participants Achieving a PASI-90 Response at Week 12

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    End point title
    		 Percentage of Participants Achieving a PASI-90 Response at Week 12
    End point description
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo Tildrakizumab 100 mg Tildrakizumab 200 mg Etanercept 50 mg
    Number of subjects analysed
    156
    307
    314
    313
    Units: Percentage of subjects
        number (not applicable)
    1.3
    38.8
    36.6
    21.4
    No statistical analyses for this end point

    Secondary: Percentage of Participants achieving a PGA score of “clear” or “minimal”, with at least a 2 grade reduction from baseline, at Week 28

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    End point title
    		 Percentage of Participants achieving a PGA score of “clear” or “minimal”, with at least a 2 grade reduction from baseline, at Week 28
    End point description
    End point type
    Secondary
    End point timeframe
    Week 28
    End point values
    		 Tildrakizumab 100 mg (Part 1 and 2) Tildrakizumab 200 mg (Part 1 and 2) Etanercept 50 mg (Part 1 and 2)
    Number of subjects analysed
    294
    299
    289
    Units: Percentage of Participant
        number (not applicable)
    64.6
    69.2
    45.3
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a PASI-100 Response at Week 12

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    End point title
    		 Percentage of Participants Achieving a PASI-100 Response at Week 12
    End point description
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo Tildrakizumab 100 mg Tildrakizumab 200 mg Etanercept 50 mg
    Number of subjects analysed
    156
    307
    314
    313
    Units: Percentage of Participants
        number (not applicable)
    0
    12.4
    11.8
    4.8
    No statistical analyses for this end point

    Secondary: Change From Baseline in the DLQI at Week 12

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    End point title
    		 Change From Baseline in the DLQI at Week 12
    End point description
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo Tildrakizumab 100 mg Tildrakizumab 200 mg Etanercept 50 mg
    Number of subjects analysed
    156
    307
    312
    312
    Units: Score on a scale
        least squares mean (confidence interval 95%)
    -2.0 (-2.9 to -1.1)
    -10.2 (-10.9 to -9.6)
    -10.3 (-11.0 to -9.7)
    -8.9 (-9.6 to -8.3)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a DLQI Score of 0 or 1 at Week 12

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    End point title
    		 Percentage of Participants With a DLQI Score of 0 or 1 at Week 12
    End point description
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo Tildrakizumab 100 mg Tildrakizumab 200 mg Etanercept 50 mg
    Number of subjects analysed
    150
    296
    306
    304
    Units: Percentage of Participant
        number (not applicable)
    8
    40.2
    47.4
    35.5
    No statistical analyses for this end point

    Secondary: Mean Change from Baseline in PASI Score at Week 12 and week 28

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    End point title
    		 Mean Change from Baseline in PASI Score at Week 12 and week 28
    End point description
    End point type
    Secondary
    End point timeframe
    Week 12 and Week 28
    End point values
    		 Placebo Tildrakizumab 100 mg Tildrakizumab 200 mg Etanercept 50 mg Placebo (Part 1) to Tildrakizumab 100 mg (Part 2) Placebo (Part 1) to Tildrakizumab 200 mg (Part 2) Tildrakizumab 100 mg (Part 1 and 2) Tildrakizumab 200 mg (Part 1 and 2) Etanercept 50 mg (Part 1 and 2)
    Number of subjects analysed
    142
    297
    302
    288
    66
    68
    290
    293
    277
    Units: Scores on a scale
        arithmetic mean (standard deviation)
    -3.4 ( 6.77 )
    -15.1 ( 7.94 )
    -15.4 ( 7.77 )
    -13.5 ( 8.29 )
    -14.5 ( 8.46 )
    -17.3 ( 8.46 )
    -16.5 ( 7.71 )
    -17.0 ( 7.81 )
    -14.8 ( 7.85 )
    No statistical analyses for this end point

    Secondary: Mean Percent Change from Baseline in PASI Score at Week 12 and Week 28

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    End point title
    		 Mean Percent Change from Baseline in PASI Score at Week 12 and Week 28
    End point description
    End point type
    Secondary
    End point timeframe
    Week 12 and Week 28
    End point values
    		 Placebo Tildrakizumab 100 mg Tildrakizumab 200 mg Etanercept 50 mg Placebo (Part 1) to Tildrakizumab 100 mg (Part 2) Placebo (Part 1) to Tildrakizumab 200 mg (Part 2) Tildrakizumab 100 mg (Part 1 and 2) Tildrakizumab 200 mg (Part 1 and 2) Etanercept 50 mg (Part 1 and 2)
    Number of subjects analysed
    142
    297
    302
    288
    66
    68
    290
    293
    277
    Units: Percent change
        arithmetic mean (standard deviation)
    -17.4 ( 32.95 )
    -74.8 ( 28.11 )
    -78.0 ( 22.31 )
    -66.7 ( 30.78 )
    -72.9 ( 30.05 )
    -84.0 ( 16.89 )
    -82.5 ( 22.33 )
    -85.7 ( 17.44 )
    -73.5 ( 24.40 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a PASI-90 Response at Week 28

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    End point title
    		 Percentage of Participants Achieving a PASI-90 Response at Week 28
    End point description
    End point type
    Secondary
    End point timeframe
    Week 28
    End point values
    		 Tildrakizumab 100 mg (Part 1 and 2) Tildrakizumab 200 mg (Part 1 and 2) Etanercept 50 mg (Part 1 and 2)
    Number of subjects analysed
    290
    293
    277
    Units: Percentage of Participant
        number (not applicable)
    55.5
    57.7
    30.7
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a PASI-100 Response at Week 28

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    End point title
    		 Percentage of Participants Achieving a PASI-100 Response at Week 28
    End point description
    End point type
    Secondary
    End point timeframe
    Week 28
    End point values
    		 Tildrakizumab 100 mg (Part 1 and 2) Tildrakizumab 200 mg (Part 1 and 2) Etanercept 50 mg (Part 1 and 2)
    Number of subjects analysed
    290
    293
    277
    Units: Percentage of Participant
        number (not applicable)
    22.8
    27.0
    11.2
    No statistical analyses for this end point

    Secondary: Change From Baseline in the DLQI at Week 28

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    End point title
    		 Change From Baseline in the DLQI at Week 28
    End point description
    End point type
    Secondary
    End point timeframe
    Week 28
    End point values
    		 Tildrakizumab 100 mg (Part 1 and 2) Tildrakizumab 200 mg (Part 1 and 2) Etanercept 50 mg (Part 1 and 2)
    Number of subjects analysed
    294
    299
    289
    Units: Score on a scale
        least squares mean (confidence interval 95%)
    -11.2 (-11.8 to -10.5)
    -11.7 (-12.3 to -11.1)
    -9.5 (-10.1 to -8.9)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a DLQI Score of 0 or 1 at Week 28

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    End point title
    		 Percentage of Participants With a DLQI Score of 0 or 1 at Week 28
    End point description
    End point type
    Secondary
    End point timeframe
    Week 28
    End point values
    		 Tildrakizumab 100 mg (Part 1 and 2) Tildrakizumab 200 mg (Part 1 and 2) Etanercept 50 mg (Part 1 and 2)
    Number of subjects analysed
    290
    297
    282
    Units: Percentage of participants
        number (not applicable)
    54.1
    65.0
    39.4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 52 weeks
    Adverse event reporting additional description
    Part 1 includes all randomized participants who received at least 1 dose of Part 1 study drug, based on the treatment received. Part 2 includes all randomized participants who received at least 1 dose of Part 2 study drug, based on the treatment received, including those on placebo re-randomized at Week 12 to tildrakizumab. Part 3 includes all part
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Placebo- Base study
    Reporting group description
    		 Participants received matching placebo to tildrakizumab SC on Weeks 0 and 4.

    Reporting group title
    Tildrakizumab 100 mg (Parts 1, 2 & 3)
    Reporting group description
    		 Participants received tildrakizumab 100 mg SC on Weeks 0, 4 and then every 12 weeks.

    Reporting group title
    Tildrakizumab 200 mg (Parts 1, 2 & 3) Wk-28 R
    Reporting group description
    		 Participants received tildrakizumab 200 mg SC on Weeks 0 and 4 (Part 1), Week 16 (Part 2), and Weeks 28 and 40 (Part 3) plus etanercept PBO twice weekly until Week 12 and once weekly from Week 12 to Week 28.

    Reporting group title
    Etanercept 50 mg
    Reporting group description
    		 Participants received etanercept 50 mg twice weekly up to Week 12 and once weekly from Week 12 to Week 28.

    Serious adverse events
    		 Placebo- Base study Tildrakizumab 100 mg (Parts 1, 2 & 3) Tildrakizumab 200 mg (Parts 1, 2 & 3) Wk-28 R Etanercept 50 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 156 (2.56%)
    30 / 487 (6.16%)
    26 / 527 (4.93%)
    20 / 313 (6.39%)
         number of deaths (all causes)
    0
    3
    0
    0
         number of deaths resulting from adverse events
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bowen's disease
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breact cancer
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma in situ
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal oncocytoma
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Breast cyst
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory arrest
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcoholism
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bipolar disorder
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Borderline personality disorder
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 156 (0.00%)
    2 / 487 (0.41%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood glucose increased
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    2 / 527 (0.38%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 156 (0.00%)
    2 / 487 (0.41%)
    2 / 527 (0.38%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy alcoholic
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid artery stenosis
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids thrombosed
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal polyp
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Steatohepatitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Psoriasis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstructive uropathy
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 156 (0.64%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    2 / 527 (0.38%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    0 / 527 (0.00%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 156 (0.00%)
    1 / 487 (0.21%)
    1 / 527 (0.19%)
    0 / 313 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Obesity
         subjects affected / exposed
    0 / 156 (0.00%)
    0 / 487 (0.00%)
    0 / 527 (0.00%)
    1 / 313 (0.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo- Base study Tildrakizumab 100 mg (Parts 1, 2 & 3) Tildrakizumab 200 mg (Parts 1, 2 & 3) Wk-28 R Etanercept 50 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    23 / 156 (14.74%)
    151 / 487 (31.01%)
    167 / 527 (31.69%)
    118 / 313 (37.70%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 156 (3.85%)
    29 / 487 (5.95%)
    30 / 527 (5.69%)
    18 / 313 (5.75%)
         occurrences all number
    6
    46
    40
    31
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    1 / 156 (0.64%)
    5 / 487 (1.03%)
    5 / 527 (0.95%)
    28 / 313 (8.95%)
         occurrences all number
    2
    5
    7
    98
    Injection site reaction
         subjects affected / exposed
    1 / 156 (0.64%)
    2 / 487 (0.41%)
    4 / 527 (0.76%)
    17 / 313 (5.43%)
         occurrences all number
    1
    2
    8
    54
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 156 (1.92%)
    26 / 487 (5.34%)
    14 / 527 (2.66%)
    10 / 313 (3.19%)
         occurrences all number
    3
    30
    17
    13
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    12 / 156 (7.69%)
    112 / 487 (23.00%)
    119 / 527 (22.58%)
    63 / 313 (20.13%)
         occurrences all number
    14
    152
    173
    79
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 156 (0.64%)
    15 / 487 (3.08%)
    27 / 527 (5.12%)
    11 / 313 (3.51%)
         occurrences all number
    1
    18
    30
    14

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Jan 2013
    Revised Objectives and endpoints
    11 Jan 2016
    Other secondary objectives and secondary efficacy endpoints revised
    24 Jul 2018
    Trial objectives, other secondary trial objectives modified

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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