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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	v2(current)
This version publication date	21 Jun 2026
First version publication date	30 Jun 2023
Other versions	v1
Version creation reason	New data added to full data set Addition of extension study data

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

MK-3222-011

ISRCTN number

US NCT number

NCT01729754

WHO universal trial number (UTN)

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

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

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?

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

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

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

993

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

A total of 1372 subjects were screened for the study, of which 282 subjects were not randomized into the study.

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

Are arms mutually exclusive

Yes

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

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

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

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 title

Base period- Part 2 (Week 12 to Week 28)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

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.

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.

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.

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.

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 title

Base period- Part 3 (Week 28 to Week 52)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

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.

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

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

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.

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.

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.

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

Period 4 title

Extension Study

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Tildrakizumab 100 mg (Extension Study)

Arm description

Tildrakizumab 100 mg every 12 Weeks

Arm type

Experimental

Investigational medicinal product name

Tildrakizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled injector, Solution for injection/infusion in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Tildrakizumab 100 mg every 12 Weeks, in either the Pre filled syringe (PFS) or Auto Injector (AI) format

Tildrakizumab 200 mg (extension study)

Arm description

Tildrakizumab 200 mg every 12 Weeks

Arm type

Experimental

Investigational medicinal product name

Tildrakizumab 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection/infusion in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Tildrakizumab 200 mg every 12 Weeks

Number of subjects in period 4	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Started	381	349
Completed	290	272
Not completed	91	77
Adverse event, serious fatal	3	1
Consent withdrawn by subject	35	24
Physician decision	8	11
Non-Compliance with Study Drug	2	2
Adverse event, non-fatal	14	11
Progressive Disease	-	2
Pregnancy	2	1
Other Protocol Specified Criteria	1	-
Lost to follow-up	15	13
missing completion/discontinuation information	1	1
Lack of efficacy	10	11

Baseline characteristics

Top of page

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

Top of page

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

Reporting group title

Tildrakizumab 200 mg (Part 1 and 2)

Reporting group description

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

Reporting group title

Tildrakizumab 100 mg (Part 1,2 and 3)

Reporting group description

Reporting group title

Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3)

Reporting group description

Reporting group title

Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)

Reporting group description

Reporting group title

Tildrakizumab 200 mg (Parts 1 & 2)/ 100 mg (Part 3)

Reporting group description

Reporting group title

Tildrakizumab 200 mg (Parts 1, 2, & 3)

Reporting group description

Reporting group title

Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)

Reporting group description

Reporting group title

Tildrakizumab 100 mg (Extension Study)

Reporting group description

Tildrakizumab 100 mg every 12 Weeks

Reporting group title

Tildrakizumab 200 mg (extension study)

Reporting group description

Tildrakizumab 200 mg every 12 Weeks

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

Top of page

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

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

Top of page

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

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

Top of page

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

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

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

Top of page

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

Top of page

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

Top of page

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

Top of page

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

Top of page

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

Top of page

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	Placebo (Part 1) to Tildrakizumab 100 mg (Part 2)	Tildrakizumab 100 mg	Placebo (Part 1) to Tildrakizumab 200 mg (Part 2)	Tildrakizumab 200 mg	Tildrakizumab 100 mg (Part 1 and 2)	Etanercept 50 mg	Tildrakizumab 200 mg (Part 1 and 2)	Etanercept 50 mg (Part 1 and 2)
Number of subjects analysed	142	66	297	68	302	290	288	293	277
Units: Scores on a scale
arithmetic mean (standard deviation)	-3.4 ( 6.77 )	-14.5 ( 8.46 )	-15.1 ( 7.94 )	-17.3 ( 8.46 )	-15.4 ( 7.77 )	-16.5 ( 7.71 )	-13.5 ( 8.29 )	-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

Top of page

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	Placebo (Part 1) to Tildrakizumab 100 mg (Part 2)	Tildrakizumab 100 mg	Placebo (Part 1) to Tildrakizumab 200 mg (Part 2)	Tildrakizumab 200 mg	Tildrakizumab 100 mg (Part 1 and 2)	Etanercept 50 mg	Tildrakizumab 200 mg (Part 1 and 2)	Etanercept 50 mg (Part 1 and 2)
Number of subjects analysed	142	66	297	68	302	290	288	293	277
Units: Percent change
arithmetic mean (standard deviation)	-17.4 ( 32.95 )	-72.9 ( 30.05 )	-74.8 ( 28.11 )	-84.0 ( 16.89 )	-78.0 ( 22.31 )	-82.5 ( 22.33 )	-66.7 ( 30.78 )	-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

Top of page

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

Top of page

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

Top of page

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

Top of page

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

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Top of page

End point title

Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

End point description

End point type

Secondary

End point timeframe

Week 60

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	373	341
Units: Proportion of subjects
number (not applicable)	0.984	0.985

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Top of page

End point title

Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

End point description

End point type

Secondary

End point timeframe

Week 112

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	346	320
Units: Proportion of subjects
number (not applicable)	0.983	0.969

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Top of page

End point title

Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

End point description

End point type

Secondary

End point timeframe

Week 172

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	317	293
Units: Proportion of subjects
number (not applicable)	0.991	0.98

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Top of page

End point title

Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

End point description

End point type

Secondary

End point timeframe

Week 220

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	294	277
Units: Proportion of subjects
number (not applicable)	0.993	0.993

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Top of page

End point title

Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

End point description

End point type

Secondary

End point timeframe

Week 268

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	102	84
Units: Proportion of subjects
number (not applicable)	0.99	1

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Top of page

End point title

Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

End point description

End point type

Secondary

End point timeframe

Week 316

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	47	34
Units: Proportion of subjects
number (not applicable)	1	1

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Top of page

End point title

Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

End point description

End point type

Secondary

End point timeframe

Week 364

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	11	9
Units: Proportion of subjects
number (not applicable)	1	1

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Top of page

End point title

Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

End point description

End point type

Secondary

End point timeframe

Week 396

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	1	0 ^[1]
Units: Proportion of subjects
number (not applicable)	1

Notes
[1] - No subjects were available for assessment at Week 396; therefore, zero subjects were analyzed.

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at week 60

Top of page

End point title

Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at week 60

End point description

End point type

Secondary

End point timeframe

Week 60

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	344	303
Units: Proportion of subjects
number (not applicable)	0.965	0.937

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) Week 112

Top of page

End point title

Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) Week 112

End point description

End point type

Secondary

End point timeframe

Week 112

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	321	286
Units: Proportion of subjects
number (not applicable)	0.919	0.878

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 220

Top of page

End point title

Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 220

End point description

End point type

Secondary

End point timeframe

Week 220

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	278	256
Units: Proportion of subjects
number (not applicable)	0.932	0.898

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 268

Top of page

End point title

Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 268

End point description

End point type

Secondary

End point timeframe

Week 268

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	93	76
Units: Proportion of subjects
number (not applicable)	0.946	0.921

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 316

Top of page

End point title

Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 316

End point description

End point type

Secondary

End point timeframe

Week 316

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	45	31
Units: Proportion of subjects
number (not applicable)	0.956	1

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 364

Top of page

End point title

Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 364

End point description

End point type

Secondary

End point timeframe

Week 364

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	11	8
Units: Proportion of subjects
number (not applicable)	1	1

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 396

Top of page

End point title

Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 396

End point description

End point type

Secondary

End point timeframe

Week 396

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	1	0 ^[2]
Units: Proportion of subjects
number (not applicable)	1

Notes
[2] - No subjects were available for assessment at Week 396; therefore, zero subjects were analyzed.

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 172

Top of page

End point title

Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 172

End point description

End point type

Secondary

End point timeframe

Week 172

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	299	267
Units: Proportion of subjects
number (not applicable)	0.936	0.903

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 60

Top of page

End point title

Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 60

End point description

End point type

Secondary

End point timeframe

Week 60

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	261	194
Units: Proportion of subjects
number (not applicable)	0.931	0.881

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 112

Top of page

End point title

Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 112

End point description

End point type

Secondary

End point timeframe

Week 112

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	245	188
Units: Proportion of subjects
number (not applicable)	0.849	0.835

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 172

Top of page

End point title

Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 172

End point description

End point type

Secondary

End point timeframe

Week 172

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	234	178
Units: Proportion of subjects
number (not applicable)	0.812	0.815

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 220

Top of page

End point title

Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 220

End point description

End point type

Secondary

End point timeframe

Week 220

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	218	171
Units: Proportion of subjects
number (not applicable)	0.807	0.766

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) Week 268

Top of page

End point title

Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) Week 268

End point description

End point type

Secondary

End point timeframe

Week 268

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	75	53
Units: Proportion of subjects
number (not applicable)	0.853	0.736

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 316

Top of page

End point title

Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 316

End point description

End point type

Secondary

End point timeframe

Week 316

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	38	20
Units: Proportion of subjects
number (not applicable)	0.816	0.8

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 364

Top of page

End point title

Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 364

End point description

End point type

Secondary

End point timeframe

Week 364

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	10	6
Units: Proportion of subjects
number (not applicable)	0.9	1

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 396

Top of page

End point title

Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 396

End point description

End point type

Secondary

End point timeframe

Week 396

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	1	0 ^[3]
Units: Proportion of subjects
number (not applicable)	1

Notes
[3] - No subjects were available for assessment at Week 396; therefore, zero subjects were analyzed.

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 60

Top of page

End point title

Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 60

End point description

End point type

Secondary

End point timeframe

Week 60

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	131	99
Units: Proportion of subjects
number (not applicable)	0.84	0.798

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 112

Top of page

End point title

Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 112

End point description

End point type

Secondary

End point timeframe

Week 112

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	123	95
Units: Proportion of subjects
number (not applicable)	0.699	0.653

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 172

Top of page

End point title

Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 172

End point description

End point type

Secondary

End point timeframe

Week 172

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	120	89
Units: Proportion of subjects
number (not applicable)	0.633	0.618

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 220

Top of page

End point title

Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 220

End point description

End point type

Secondary

End point timeframe

Week 220

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	112	86
Units: Proportion of subjects
number (not applicable)	0.67	0.558

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 268

Top of page

End point title

Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 268

End point description

End point type

Secondary

End point timeframe

Week 268

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	38	29
Units: Proportion of subjects
number (not applicable)	0.684	0.586

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 316

Top of page

End point title

Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 316

End point description

End point type

Secondary

End point timeframe

Week 316

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	19	9
Units: Proportion of subjects
number (not applicable)	0.737	0.667

No statistical analyses for this end point

Secondary: Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 364

Top of page

End point title

Proportion of Subjects With PASI 100 Response Over Time Among PASI 100 Responders at Week 52 (Extension Study) at Week 364

End point description

End point type

Secondary

End point timeframe

Week 364

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	4	3
Units: Proportion of subjects
number (not applicable)	0.75	1

No statistical analyses for this end point

Secondary: Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 60

Top of page

End point title

Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 60

End point description

End point type

Secondary

End point timeframe

Week 60

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	376	344
Units: score on a scale
arithmetic mean (standard deviation)	-18.2 ( 7.53 )	-17.3 ( 6.86 )

No statistical analyses for this end point

Secondary: Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 112

Top of page

End point title

Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 112

End point description

End point type

Secondary

End point timeframe

Week 112

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	349	323
Units: score on a scale
arithmetic mean (standard deviation)	-17.8 ( 7.38 )	-17.1 ( 6.79 )

No statistical analyses for this end point

Secondary: Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 172

Top of page

End point title

Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 172

End point description

End point type

Secondary

End point timeframe

Week 172

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	320	295
Units: score on a scale
arithmetic mean (standard deviation)	-18.0 ( 7.16 )	-17.1 ( 6.97 )

No statistical analyses for this end point

Secondary: Change From Baseline in Psoriasis Area and Severity Index Score Over Time at Week 220(Extension Study)

Top of page

End point title

Change From Baseline in Psoriasis Area and Severity Index Score Over Time at Week 220(Extension Study)

End point description

End point type

Secondary

End point timeframe

Week 220

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	296	279
Units: score on a scale
arithmetic mean (standard deviation)	-18.0 ( 7.06 )	-17.1 ( 6.73 )

No statistical analyses for this end point

Secondary: Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 268

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End point title

Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 268

End point description

End point type

Secondary

End point timeframe

Week 268

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	103	85
Units: score on a scale
arithmetic mean (standard deviation)	-18.5 ( 6.87 )	-18.0 ( 6.80 )

No statistical analyses for this end point

Secondary: Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 316

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End point title

Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 316

End point description

End point type

Secondary

End point timeframe

Week 316

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	48	35
Units: score on a scale
arithmetic mean (standard deviation)	-18.0 ( 6.33 )	-16.8 ( 4.30 )

No statistical analyses for this end point

Secondary: Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 364

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End point title

Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 364

End point description

End point type

Secondary

End point timeframe

Week 364

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	11	9
Units: score on a scale
arithmetic mean (standard deviation)	-16.6 ( 3.80 )	-19.5 ( 5.50 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 60

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End point title

Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 60

End point description

End point type

Secondary

End point timeframe

Week 60

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	378	345
Units: score on a scale
arithmetic mean (standard deviation)	-91.4 ( 12.97 )	-89.0 ( 13.11 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 112

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End point title

Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 112

End point description

End point type

Secondary

End point timeframe

Week 112

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	349	323
Units: score on a scale
arithmetic mean (standard deviation)	-89.5 ( 14.67 )	-88.3 ( 14.92 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 172

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End point title

Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 172

End point description

End point type

Secondary

End point timeframe

Week 172

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	320	295
Units: score on a scale
arithmetic mean (standard deviation)	-90.9 ( 15.05 )	-89.2 ( 14.61 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 220

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End point title

Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 220

End point description

End point type

Secondary

End point timeframe

Week 220

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	296	279
Units: score on a scale
arithmetic mean (standard deviation)	-91.8 ( 11.49 )	-89.7 ( 12.23 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 268

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End point title

Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 268

End point description

End point type

Secondary

End point timeframe

Week 268

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	103	85
Units: score on a scale
arithmetic mean (standard deviation)	-92.3 ( 10.83 )	-91.3 ( 10.72 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 316

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End point title

Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 316

End point description

End point type

Secondary

End point timeframe

Week 316

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	48	35
Units: score on a scale
arithmetic mean (standard deviation)	-93.1 ( 10.34 )	-94.8 ( 6.76 )

No statistical analyses for this end point

Secondary: Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 364

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End point title

Percent Change From Baseline in Psoriasis Area and Severity Index Score Over Time (Extension Study) at Week 364

End point description

End point type

Secondary

End point timeframe

Week 364

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	11	9
Units: score on a scale
arithmetic mean (standard deviation)	-95.9 ( 5.85 )	-96.7 ( 7.32 )

No statistical analyses for this end point

Secondary: Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 60

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End point title

Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 60

End point description

End point type

Secondary

End point timeframe

Week 60

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	374	342
Units: Percentage of Subjects
number (not applicable)	74.1	70.8

No statistical analyses for this end point

Secondary: Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 112

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End point title

Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 112

End point description

End point type

Secondary

End point timeframe

Week 112

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	346	320
Units: Percentage of subjects
number (not applicable)	63.9	65.3

No statistical analyses for this end point

Secondary: Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 172

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End point title

Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 172

End point description

End point type

Secondary

End point timeframe

Week 172

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	316	292
Units: Percentage of subjects
number (not applicable)	70.3	62.3

No statistical analyses for this end point

Secondary: Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 220

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End point title

Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 220

End point description

End point type

Secondary

End point timeframe

Week 220

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	292	275
Units: Percentage of subjects
number (not applicable)	73.3	64.4

No statistical analyses for this end point

Secondary: Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 268

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End point title

Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 268

End point description

End point type

Secondary

End point timeframe

Week 268

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	101	84
Units: Percentage of subjects
number (not applicable)	75.2	69.0

No statistical analyses for this end point

Secondary: Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 364

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End point title

Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline (Extension Study) at Week 364

End point description

End point type

Secondary

End point timeframe

Week 364

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	11	9
Units: Percentage of subjects
number (not applicable)	72.7	88.9

No statistical analyses for this end point

Secondary: Percentage of Subjects With a PASI75 Response Over Time (Extension Study) at Week 60

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End point title

Percentage of Subjects With a PASI75 Response Over Time (Extension Study) at Week 60

End point description

End point type

Secondary

End point timeframe

Week 60

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	378	345
Units: Percentage of subjects
number (not applicable)	91.3	86.7

No statistical analyses for this end point

Secondary: Percentage of Subjects With a PASI75 Response Over Time (Extension Study) at Week 112

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End point title

Percentage of Subjects With a PASI75 Response Over Time (Extension Study) at Week 112

End point description

End point type

Secondary

End point timeframe

Week 112

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	349	323
Units: Percentage of subjects
number (not applicable)	86.8	83.3

No statistical analyses for this end point

Secondary: Percentage of Subjects With a PASI75 Response Over Time (Extension Study) at Week 172

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End point title

Percentage of Subjects With a PASI75 Response Over Time (Extension Study) at Week 172

End point description

End point type

Secondary

End point timeframe

Week 172

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	320	295
Units: Percentage of subjects
number (not applicable)	91.3	86.1

No statistical analyses for this end point

Secondary: Percentage of Subjects With a PASI75 Response Over Time (Extension Study) at Week 220

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End point title

Percentage of Subjects With a PASI75 Response Over Time (Extension Study) at Week 220

End point description

End point type

Secondary

End point timeframe

220

End point values	Tildrakizumab 100 mg (Extension Study)	Tildrakizumab 200 mg (extension study)
Number of subjects analysed	296	279
Units: Percentage of subjects
number (not applicable)	90.2	86.7

No statistical analyses for this end point

Adverse events

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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 name

MedDRA

Dictionary version

19.1

Reporting group title

Placebo- Base study

Reporting group description

Participants received matching placebo to tildrakizumab SC on Weeks 0 and 4.

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.

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

Tildrakizumab 100 mg - Extension Study

Reporting group description

Reporting group title

Tildrakizumab 200 mg - Extension Study

Reporting group description

Serious adverse events	Placebo- Base study	Etanercept 50 mg	Tildrakizumab 100 mg (Parts 1, 2 & 3)	Tildrakizumab 200 mg (Parts 1, 2 & 3) Wk-28 R	Tildrakizumab 100 mg - Extension Study	Tildrakizumab 200 mg - Extension Study
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 156 (2.56%)	20 / 313 (6.39%)	30 / 487 (6.16%)	26 / 527 (4.93%)	87 / 381 (22.83%)	79 / 349 (22.64%)
number of deaths (all causes)	0	0	3	0	2	1
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%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Bladder transitional cell carcinoma
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Bowen's disease
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Breast cancer
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Lung adenocarcinoma
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant melanoma in situ
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Renal oncocytoma
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Thyroid cancer
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Basal cell carcinoma
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	3 / 381 (0.79%)	4 / 349 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	1 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bladder cancer
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Breast cancer metastatic
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Colon cancer
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Enchondromatosis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Hepatic adenoma
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Lipoma
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Ovarian cancer
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Testicular neoplasm
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Uterine leiomyoma
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	2 / 381 (0.52%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	2 / 381 (0.52%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Hypertensive crisis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Varicose vein
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	2 / 381 (0.52%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Cataract
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	2 / 349 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
High frequency ablation
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Pregnancy, puerperium and perinatal conditions
Gestational diabetes
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Death
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0
Haematoma
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Impaired healing
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Non-cardiac chest pain
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Breast cyst
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Adenomyosis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Benign prostatic hyperplasia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Uterine haemorrhage
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Uterovaginal prolapse
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Sleep apnoea syndrome
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asphyxia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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 / 1
Asthma
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Haemothorax
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Laryngeal granuloma
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Nasal septum deviation
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nasal turbinate hypertrophy
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Psychiatric disorders
Alcoholism
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Bipolar disorder
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Borderline personality disorder
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	2 / 487 (0.41%)	0 / 527 (0.00%)	2 / 381 (0.52%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Alcohol use disorder
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Completed suicide
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	2 / 381 (0.52%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
Drug dependence
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Insomnia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Product issues
Device dislocation
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Hepatobiliary disorders
Bile duct stone
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	4 / 381 (1.05%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Steatohepatitis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Cholecystitis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Investigations
Blood glucose increased
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Hand fracture
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Humerus fracture
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Meniscus injury
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	2 / 349 (0.57%)
occurrences causally related to treatment / all	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
Tendon rupture
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	2 / 527 (0.38%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 2	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bone contusion
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Chest injury
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Facial bones fracture
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Foot fracture
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Incisional hernia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Ligament rupture
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Limb injury
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Lower limb fracture
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Multiple fractures
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Multiple injuries
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Patella fracture
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Thoracic vertebral fracture
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Toxicity to various agents
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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 / 1	0 / 0
Traumatic intracranial haematoma
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Wrist fracture
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Congenital, familial and genetic disorders
Keratosis follicular
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	2 / 487 (0.41%)	2 / 527 (0.38%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Cardiac failure
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Cardiac failure congestive
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiomyopathy alcoholic
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Coronary artery disease
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	2 / 381 (0.52%)	2 / 349 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	2 / 349 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Mitral valve incompetence
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Myocardial infarction
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	1 / 156 (0.64%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Acute myocardial infarction
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	3 / 349 (0.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Atrial tachycardia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Atrioventricular block second degree
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Myocardial ischaemia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Myocarditis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Supraventricular tachycardia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Nervous system disorders
Carotid artery stenosis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radiculopathy
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Carpal tunnel syndrome
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Cerebral ischaemia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Cerebrovascular accident
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	2 / 381 (0.52%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Epilepsy
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Facial paresis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Intensive care unit acquired weakness
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Intracranial aneurysm
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Ischaemic cerebral infarction
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Ischaemic stroke
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	2 / 381 (0.52%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar radiculopathy
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Syncope
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Eye disorders
Optic ischaemic neuropathy
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Gastrointestinal disorders
Abdominal hernia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Abdominal pain
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Dyspepsia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Gastritis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Haemorrhoids thrombosed
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Oesophageal polyp
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Abdominal pain upper
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Diverticulum intestinal
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Duodenal ulcer haemorrhage
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Enterocolitis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Gastric perforation
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Gastric ulcer haemorrhage
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Gastritis erosive
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Hiatus hernia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Inguinal hernia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine polyp
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Malocclusion
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Mesenteric artery thrombosis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Pancreatitis acute
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Psoriasis
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Drug eruption
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Duodenal polyp
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	1 / 381 (0.26%)	3 / 349 (0.86%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive uropathy
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Ureterolithiasis
subjects affected / exposed	1 / 156 (0.64%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Acute kidney injury
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Calculus urinary
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	2 / 381 (0.52%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis noninfective
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Goitre
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Thyrotoxic crisis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Cervical spinal stenosis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Intervertebral disc disorder
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Intervertebral disc protrusion
subjects affected / exposed	1 / 156 (0.64%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	3 / 381 (0.79%)	2 / 349 (0.57%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spondylolisthesis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Bursitis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Intervertebral disc degeneration
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Patellofemoral pain syndrome
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	3 / 381 (0.79%)	2 / 349 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	1 / 3	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 156 (0.64%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	2 / 527 (0.38%)	3 / 381 (0.79%)	2 / 349 (0.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	1 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Pneumonia
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	2 / 381 (0.52%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Sepsis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Sinusitis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Urosepsis
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	1 / 487 (0.21%)	1 / 527 (0.19%)	0 / 381 (0.00%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal wall abscess
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Chronic sinusitis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related sepsis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Epididymitis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Gastroenteritis bacterial
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Infected dermal cyst
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Large intestine infection
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Meningitis viral
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Otitis media acute
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Peritonitis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Tonsillitis
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Viral infection
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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
Metabolism and nutrition disorders
Obesity
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Jaw cyst
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Overweight
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Tetany
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	0 / 381 (0.00%)	1 / 349 (0.29%)
occurrences causally related to treatment / all	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
Type 2 diabetes mellitus
subjects affected / exposed	0 / 156 (0.00%)	0 / 313 (0.00%)	0 / 487 (0.00%)	0 / 527 (0.00%)	1 / 381 (0.26%)	0 / 349 (0.00%)
occurrences causally related to treatment / all	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

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo- Base study	Etanercept 50 mg	Tildrakizumab 100 mg (Parts 1, 2 & 3)	Tildrakizumab 200 mg (Parts 1, 2 & 3) Wk-28 R	Tildrakizumab 100 mg - Extension Study	Tildrakizumab 200 mg - Extension Study
Total subjects affected by non serious adverse events
subjects affected / exposed	23 / 156 (14.74%)	118 / 313 (37.70%)	151 / 487 (31.01%)	167 / 527 (31.69%)	344 / 381 (90.29%)	333 / 349 (95.42%)
Vascular disorders
Hypertension
subjects affected / exposed	5 / 156 (3.21%)	9 / 313 (2.88%)	17 / 487 (3.49%)	12 / 527 (2.28%)	49 / 381 (12.86%)	59 / 349 (16.91%)
occurrences all number	5	9	17	12	55	77
Nervous system disorders
Headache
subjects affected / exposed	6 / 156 (3.85%)	18 / 313 (5.75%)	29 / 487 (5.95%)	30 / 527 (5.69%)	37 / 381 (9.71%)	44 / 349 (12.61%)
occurrences all number	6	31	46	40	77	76
General disorders and administration site conditions
Injection site erythema
subjects affected / exposed	1 / 156 (0.64%)	28 / 313 (8.95%)	5 / 487 (1.03%)	5 / 527 (0.95%)	7 / 381 (1.84%)	15 / 349 (4.30%)
occurrences all number	2	98	5	7	7	42
Injection site reaction
subjects affected / exposed	1 / 156 (0.64%)	17 / 313 (5.43%)	2 / 487 (0.41%)	4 / 527 (0.76%)	7 / 381 (1.84%)	5 / 349 (1.43%)
occurrences all number	1	54	2	8	13	5
Pyrexia
subjects affected / exposed	2 / 156 (1.28%)	5 / 313 (1.60%)	10 / 487 (2.05%)	3 / 527 (0.57%)	19 / 381 (4.99%)	8 / 349 (2.29%)
occurrences all number	3	5	11	3	20	8
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	2 / 156 (1.28%)	8 / 313 (2.56%)	22 / 487 (4.52%)	20 / 527 (3.80%)	45 / 381 (11.81%)	35 / 349 (10.03%)
occurrences all number	2	11	24	25	63	49
Nausea
subjects affected / exposed	1 / 156 (0.64%)	3 / 313 (0.96%)	15 / 487 (3.08%)	11 / 527 (2.09%)	20 / 381 (5.25%)	14 / 349 (4.01%)
occurrences all number	1	5	16	12	27	17
Toothache
subjects affected / exposed	1 / 156 (0.64%)	4 / 313 (1.28%)	12 / 487 (2.46%)	8 / 527 (1.52%)	23 / 381 (6.04%)	11 / 349 (3.15%)
occurrences all number	1	5	12	8	27	11
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	3 / 156 (1.92%)	8 / 313 (2.56%)	14 / 487 (2.87%)	19 / 527 (3.61%)	34 / 381 (8.92%)	28 / 349 (8.02%)
occurrences all number	3	8	15	20	34	28
Oropharyngeal pain
subjects affected / exposed	3 / 156 (1.92%)	8 / 313 (2.56%)	8 / 487 (1.64%)	14 / 527 (2.66%)	24 / 381 (6.30%)	23 / 349 (6.59%)
occurrences all number	3	8	8	15	31	30
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	3 / 156 (1.92%)	11 / 313 (3.51%)	11 / 487 (2.26%)	15 / 527 (2.85%)	17 / 381 (4.46%)	26 / 349 (7.45%)
occurrences all number	3	23	11	18	22	40
Psoriasis
subjects affected / exposed	4 / 156 (2.56%)	11 / 313 (3.51%)	5 / 487 (1.03%)	4 / 527 (0.76%)	23 / 381 (6.04%)	14 / 349 (4.01%)
occurrences all number	4	11	5	5	26	17
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	3 / 156 (1.92%)	10 / 313 (3.19%)	26 / 487 (5.34%)	14 / 527 (2.66%)	51 / 381 (13.39%)	65 / 349 (18.62%)
occurrences all number	3	13	30	17	70	98
Osteoarthritis
subjects affected / exposed	0 / 156 (0.00%)	1 / 313 (0.32%)	0 / 487 (0.00%)	6 / 527 (1.14%)	15 / 381 (3.94%)	18 / 349 (5.16%)
occurrences all number	0	1	0	6	17	19
Back pain
subjects affected / exposed	3 / 156 (1.92%)	9 / 313 (2.88%)	21 / 487 (4.31%)	19 / 527 (3.61%)	46 / 381 (12.07%)	46 / 349 (13.18%)
occurrences all number	3	10	22	19	52	55
Pain in extremity
subjects affected / exposed	2 / 156 (1.28%)	3 / 313 (0.96%)	15 / 487 (3.08%)	6 / 527 (1.14%)	19 / 381 (4.99%)	13 / 349 (3.72%)
occurrences all number	2	3	15	7	27	16
Infections and infestations
Nasopharyngitis
subjects affected / exposed	12 / 156 (7.69%)	63 / 313 (20.13%)	112 / 487 (23.00%)	119 / 527 (22.58%)	186 / 381 (48.82%)	168 / 349 (48.14%)
occurrences all number	14	79	152	174	471	472
Upper respiratory tract infection
subjects affected / exposed	1 / 156 (0.64%)	11 / 313 (3.51%)	15 / 487 (3.08%)	27 / 527 (5.12%)	41 / 381 (10.76%)	47 / 349 (13.47%)
occurrences all number	1	14	18	30	75	83
Bronchitis
subjects affected / exposed	0 / 156 (0.00%)	5 / 313 (1.60%)	14 / 487 (2.87%)	20 / 527 (3.80%)	34 / 381 (8.92%)	43 / 349 (12.32%)
occurrences all number	0	5	15	21	49	65
Influenza
subjects affected / exposed	3 / 156 (1.92%)	5 / 313 (1.60%)	12 / 487 (2.46%)	16 / 527 (3.04%)	35 / 381 (9.19%)	41 / 349 (11.75%)
occurrences all number	3	5	15	18	50	51
Sinusitis
subjects affected / exposed	1 / 156 (0.64%)	4 / 313 (1.28%)	20 / 487 (4.11%)	15 / 527 (2.85%)	36 / 381 (9.45%)	25 / 349 (7.16%)
occurrences all number	1	7	22	16	58	43
Urinary tract infection
subjects affected / exposed	4 / 156 (2.56%)	12 / 313 (3.83%)	8 / 487 (1.64%)	10 / 527 (1.90%)	30 / 381 (7.87%)	28 / 349 (8.02%)
occurrences all number	4	13	8	12	44	42
Gastroenteritis
subjects affected / exposed	1 / 156 (0.64%)	8 / 313 (2.56%)	10 / 487 (2.05%)	9 / 527 (1.71%)	30 / 381 (7.87%)	27 / 349 (7.74%)
occurrences all number	1	8	11	9	37	30
Rhinitis
subjects affected / exposed	1 / 156 (0.64%)	5 / 313 (1.60%)	8 / 487 (1.64%)	10 / 527 (1.90%)	21 / 381 (5.51%)	21 / 349 (6.02%)
occurrences all number	1	5	10	10	38	34
Pharyngitis
subjects affected / exposed	1 / 156 (0.64%)	4 / 313 (1.28%)	9 / 487 (1.85%)	4 / 527 (0.76%)	20 / 381 (5.25%)	11 / 349 (3.15%)
occurrences all number	1	4	10	5	22	17

More information

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Were there any global substantial amendments to the protocol? Yes

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

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Change From Baseline in the DLQI at Week 12

Secondary: Change From Baseline in the DLQI at Week 12

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

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

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

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

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

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

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

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

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

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

Secondary: Change From Baseline in the DLQI at Week 28

Secondary: Change From Baseline in the DLQI at Week 28

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

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

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 50 Response Over Time Among PASI 50 Responders at Week 52 (Extension Study)

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at week 60

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at week 60

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) Week 112

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) Week 112

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 220

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 220

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 268

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 268

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 316

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 316

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 364

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 364

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 396

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 396

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 172

Secondary: Proportion of Subjects With PASI 75 Response Over Time Among PASI 75 Responders at Week 52 (Extension Study) at Week 172

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 60

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 60

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 112

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 112

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 172

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 172

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 220

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 220

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) Week 268

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) Week 268

Secondary: Proportion of Subjects With PASI 90 Response Over Time Among PASI 90 Responders at Week 52 (Extension Study) at Week 316