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

Summary
EudraCT number	2014-000720-18
Trial protocol	DE CZ PL ES
Global end of trial date	01 Jul 2020

Results information
Results version number	v1(current)
This version publication date	16 Jul 2021
First version publication date	16 Jul 2021
Other versions

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

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Trial information

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Sponsor protocol code

CNTO1959PSO3002

ISRCTN number

US NCT number

NCT02207244

WHO universal trial number (UTN)

Sponsor organisation name

Janssen Pharmaceutical

Sponsor organisation address

1400 McKean Rd., Spring House, United States,

Public contact

Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com

Scientific contact

Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.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

01 Jul 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

01 Jul 2020

Was the trial ended prematurely?

Main objective of the trial

The main objectives of this study were to evaluate the efficacy, safety, and tolerability of guselkumab in the treatment of subjects with moderate to severe plaque-type psoriasis.

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. The safety and tolerability of guselkumab and adalimumab were monitored by collecting information on adverse events (AEs), including injection-site reactions (ISRs) and allergic reactions, clinical laboratory tests, physical examinations, vital signs, electrocardiograms (ECGs), concomitant medication review, and early detection of active tuberculosis (TB).

Background therapy

Evidence for comparator

Actual start date of recruitment

03 Nov 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 51

Country: Number of subjects enrolled

Canada: 130

Country: Number of subjects enrolled

Czechia: 31

Country: Number of subjects enrolled

Germany: 84

Country: Number of subjects enrolled

Spain: 43

Country: Number of subjects enrolled

Korea, Republic of: 98

Country: Number of subjects enrolled

Poland: 265

Country: Number of subjects enrolled

Russian Federation: 100

Country: Number of subjects enrolled

United States: 190

Worldwide total number of subjects

992

EEA total number of subjects

423

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)

949

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 1279 subjects were screened. Of these 1279, 992 subjects were randomized.

Period 1 title

Placebo Controlled Period: Week 0 - 16

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo (Week 0 - 16)

Arm description

Subjects received placebo matched to guselkumab subcutaneous (SC) injection at Weeks 0, 4, and 12 and placebo matched to adalimumab (2 SC injections) at Week 0, followed by placebo matched to adalimumab (1 SC injection) at Week 1 and every other week thereafter through Week 15 to maintain the blind during placebo controlled period (PCP).

Arm type

Placebo

Investigational medicinal product name

Placebo (for guselkumab)

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection in pre-filled syringe, Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo matching to guselkumab was administered subcutaneously at Weeks 0, 4 and 12 in PCP.

Investigational medicinal product name

Placebo (for adalimumab)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo matching to adalimumab was administered subcutaneously (2 doses) at Week 0 followed by single subcutaneous dose thereafter through Week 15 in PCP.

Guselkumab 100 mg (Week 0 - 16)

Arm description

Subjects received guselkumab 100 milligram (mg) SC injection at Weeks 0, 4 and 12, and placebo matched to adalimumab (2 SC injections) at Week 0 followed by placebo matched to adalimumab (1 SC injection) at Week 1 and every other week thereafter through Week 15 during PCP.

Arm type

Experimental

Investigational medicinal product name

Guselkumab

Investigational medicinal product code

Other name

CNTO1959

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Guselkumab 100 mg was administered subcutaneously at Weeks 0, 4, and 12.

Adalimumab (Week 0 - 16)

Arm description

Subjects received adalimumab 80 mg (2 SC injections) at Week 0 followed by adalimumab 40 mg (1 SC injection) at Week 1 and every other week thereafter through Week 15 and placebo matched to guselkumab SC injection at Weeks 0, 4, and 12 during PCP.

Arm type

Active comparator

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Adalimumab 80 mg was administered subcutaneously (2 doses) at Week 0 followed by single subcutaneous dose of adalimumab 40 mg at Week 1 and thereafter through Week 15.

Number of subjects in period 1	Placebo (Week 0 - 16)	Guselkumab 100 mg (Week 0 - 16)	Adalimumab (Week 0 - 16)
Started	248	496	248
Completed	233	478	237
Not completed	15	18	11
Consent withdrawn by subject	7	1	-
Adverse event, non-fatal	2	9	4
Unspecified	-	2	2
Lost to follow-up	1	3	2
Lack of efficacy	4	-	2
Protocol deviation	1	3	1

Period 2 title

Placebo crossover and ACP: Week 16 - 28

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo then Guselkumab 100 mg (Week 16 - 28)

Arm description

Subjects who started receiving placebo in the first period were crossed over to receive guselkumab 100 mg SC injection at Weeks 16 and 20 and placebo matched to adalimumab (1 SC injection) at Weeks 17, 19, 21, and 23 during the active comparator controlled period (ACP).

Arm type

Placebo

Investigational medicinal product name

Placebo (for adalimumab)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo matching to adalimumab was administered subcutaneously at Weeks 17, 19, 21, 23, and q2w in active controlled period.

Investigational medicinal product name

Guselkumab

Investigational medicinal product code

Other name

CNTO1959

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Guselkumab 100 mg was administered subcutaneously to subjects receiving matching placebo in PCP and crossed over to receive guselkumab in ACP.

Guselkumab 100 mg (Week 16 - 28)

Arm description

Subjects who started receiving guselkumab in the first period, received placebo matched to guselkumab SC injection at Week 16 followed by guselkumab 100 mg SC injection at Week 20 and placebo matched to adalimumab (1 SC injection) at Weeks 17, 19, 21 and 23.

Arm type

Experimental

Investigational medicinal product name

Guselkumab

Investigational medicinal product code

Other name

CNTO1959

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Guselkumab 100 mg was administered subcutaneously q8w in ACP to subjects initially receiving guselkumab 100 mg in PCP.

Adalimumab (Week 16 - 28)

Arm description

Subjects who received adalimumab in the first period, continued to receive adalimumab 40 mg (1 SC injection) every 2 weeks (q2w) from Week 17 through Week 23 and placebo matched to guselkumab SC injection at Weeks 16 and 20.

Arm type

Active comparator

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Adalimumab 40 mg was administered to subcutaneously q2w in ACP to subjects who were initially receiving adalimumab in PCP.

Number of subjects in period 2	Placebo then Guselkumab 100 mg (Week 16 - 28)	Guselkumab 100 mg (Week 16 - 28)	Adalimumab (Week 16 - 28)
Started	233	478	237
Completed	227	470	228
Not completed	6	8	9
Consent withdrawn by subject	3	3	2
Adverse event, non-fatal	-	3	2
Unspecified	1	-	-
Lost to follow-up	1	2	2
Protocol deviation	1	-	1
Lack of efficacy	-	-	2

Period 3 title

Withdrawal and Re-treatment: Week 28-72

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo then Guselkumab 100 mg (Week 28 - 72)

Arm description

Subjects assigned to the placebo, then guselkumab arm through Week 28 were assessed for psoriasis area and severity index (PASI) 90 response at Week 28. Subjects who were PASI 90 non-responders received guselkumab 100 mg SC injection at Week 28 and then every 8 weeks (q8w) thereafter through Week 72 and placebo matched to guselkumab SC injection at Week 32 and then q8w through Week 72. Subjects who were PASI 90 responders at Week 28 received placebo matched to guselkumab SC injection at Week 28 and every 4 weeks (q4w) thereafter through Week 72 or until loss of greater than or equal to (>=) 50 percentage (%) in the improvement in PASI (Withdrawal and retreatment period). If they lost response according to this definition, they were retreated with guselkumab.

Arm type

Placebo

Investigational medicinal product name

Guselkumab

Investigational medicinal product code

Other name

CNTO1959

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Guselkumab 100 mg was administered subcutaneously to PASI 90 non-responders at Week 28 and then q8w thereafter through Week 72.

Investigational medicinal product name

Placebo (for guselkumab)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo matching to guselkumab was administered subcutaneously to PASI 90 non-responders at Week 32 and then q8w through Week 72 whereas placebo matching to guselkumab was administered subcutaneously to PASI 90 responders at Week 28 and q4w thereafter through Week 72 or until loss of >=50% the improvement in PASI.

Guselkumab 100 mg (Week 28 - 72)

Arm description

Subjects assigned to the guselkumab arm through Week 28 were assessed for PASI 90 response at Week 28. Subjects who were PASI 90 non-responders at Week 28 received guselkumab 100 mg SC injection at Week 28 and q8w thereafter through Week 72 and placebo matched to guselkumab at Week 32 and then q8w through Week 72. Subjects who were PASI 90 responders were re-randomized to either guselkumab or placebo. Subjects re-randomized to guselkumab, received guselkumab 100 mg SC injection at Week 28 and q8w thereafter through Week 72 and placebo matched to guselkumab SC injection at Weeks 32 and then q8w through Week 72. Subjects re-randomized to placebo, received placebo matched to guselkumab SC injection q4w through Week 72 or until loss of >=50% in the improvement in PASI (Withdrawal and retreatment period). If they lost response according to this definition, they were retreated with guselkumab.

Arm type

Experimental

Investigational medicinal product name

Guselkumab

Investigational medicinal product code

Other name

CNTO1959

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Guselkumab 100 mg was administered subcutaneously to PASI 90 non-responders at Week 28 and q8w thereafter through Week 72 whereas PASI 90 responders were re-randomized to guselkumab through Week 72.

Adalimumab then Guselkumab 100 mg (Week 28 - 72)

Arm description

Subjects who were assigned to the adalimumab arm through Week 28 were assessed for PASI 90 response at Week 28. Subjects who were PASI 90 non-responders at Week 28 received guselkumab 100 mg SC injection at Week 28 and 32 and q8w thereafter through Week 72 and placebo matched to guselkumab SC injection at Weeks 36 and 44. Subjects who were PASI 90 responders, received placebo matched to guselkumab SC injection q4w thereafter through Week 72 or until loss of >=50% in the improvement in PASI (Withdrawal and retreatment period). If they lost response according to this definition, they were treated with guselkumab.

Arm type

Active comparator

Investigational medicinal product name

Guselkumab

Investigational medicinal product code

Other name

CNTO1959

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Guselkumab 100 mg was administered subcutaneously to PASI 90 non-responders at Week 28 and 32 and q8w thereafter through Week 72.

Adalimumab (After ACP)

Arm description

Subjects who received adalimumab 80 mg at Week 0 and adalimumab 40 mg at Week 1 and every other week through Week 23 were assessed for PASI 90 response at Week 28. PASI 90 responders who did not crossover to guselkumab upon loss of >=50% in the improvement in PASI and did not continue any treatment at Week 28 are reported in this arm.

Arm type

Active comparator

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Adalimumab 40 mg was administered subcutaneously to subjects through Week 23.

Number of subjects in period 3	Placebo then Guselkumab 100 mg (Week 28 - 72)	Guselkumab 100 mg (Week 28 - 72)	Adalimumab then Guselkumab 100 mg (Week 28 - 72)	Adalimumab (After ACP)
Started	227	470	220	8
Nonresponders	80 ^[1]	95 ^[2]	112 ^[3]	0
Responders at Week (Wk) 28	0 ^[4]	375 ^[5]	0 ^[6]	0
Responders at Wk 28, withdrawn treatment	147 ^[7]	0 ^[8]	108 ^[9]	0
Completed	213	443	211	0
Not completed	14	27	9	8
Consent withdrawn by subject	2	7	2	2
Adverse event, non-fatal	1	5	3	2
Pregnancy	-	2	-	-
Unspecified	-	2	-	-
Subjects not retreated with guselkumab	8	-	-	-
Lost to follow-up	2	7	-	2
Lack of efficacy	1	3	2	2
Protocol deviation	-	1	1	-
Noncompliance	-	-	1	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: There were only specified number of subjects in each arm of each milestone.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: There were only specified number of subjects in each arm of each milestone.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: There were only specified number of subjects in each arm of each milestone.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: There were only specified number of subjects in each arm of each milestone.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: There were only specified number of subjects in each arm of each milestone.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: There were only specified number of subjects in each arm of each milestone.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: There were only specified number of subjects in each arm of each milestone.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: There were only specified number of subjects in each arm of each milestone.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: There were only specified number of subjects in each arm of each milestone.

Period 4 title

Open-label Guselkumab: Week 72-264

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Guselkumab Combined

Arm description

All subjects who received guselkumab 100 mg subcutaneously q8w at Week 76 and thereafter through Week 252.

Arm type

Experimental

Investigational medicinal product name

Guselkumab

Investigational medicinal product code

Other name

CNTO1959

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Guselkumab 100 mg was administered subcutaneously at Week 76 and then q8w through Week 252.

Adalimumab then Guselkumab 100 mg (Week 72 - 264)

Arm description

All subjects received guselkumab 100 mg at Week 76 and then q8w through Week 252.

Arm type

Experimental

Investigational medicinal product name

Guselkumab

Investigational medicinal product code

Other name

CNTO1959

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Guselkumab 100 mg was administered subcutaneously at Week 76 and then q8w through Week 252.

Number of subjects in period 4	Guselkumab Combined	Adalimumab then Guselkumab 100 mg (Week 72 - 264)
Started	656	211
Completed	554	173
Not completed	102	38
Adverse event, serious fatal	1	1
Consent withdrawn by subject	30	10
Adverse event, non-fatal	21	12
Pregnancy	2	-
Unspecified	19	8
Lost to follow-up	26	5
Lack of efficacy	3	2

Baseline characteristics

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Reporting group title

Placebo (Week 0 - 16)

Reporting group description

Reporting group title

Guselkumab 100 mg (Week 0 - 16)

Reporting group description

Reporting group title

Adalimumab (Week 0 - 16)

Reporting group description

Reporting group values	Placebo (Week 0 - 16)	Guselkumab 100 mg (Week 0 - 16)	Adalimumab (Week 0 - 16)	Total
Number of subjects	248	496	248	992
Title for AgeCategorical
Units: subjects
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	239	473	237	949
From 65 to 84 years	9	23	11	43
85 years and over	0	0	0	0
Title for AgeContinuous
Units: years
arithmetic mean (standard deviation)	43.3 ( 12.38 )	43.7 ( 12.23 )	43.2 ( 11.92 )	-
Title for Gender
Units: subjects
Female	75	147	78	300
Male	173	349	170	692

End points

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Reporting group title

Placebo (Week 0 - 16)

Reporting group description

Reporting group title

Guselkumab 100 mg (Week 0 - 16)

Reporting group description

Reporting group title

Adalimumab (Week 0 - 16)

Reporting group description

Reporting group title

Placebo then Guselkumab 100 mg (Week 16 - 28)

Reporting group description

Reporting group title

Guselkumab 100 mg (Week 16 - 28)

Reporting group description

Reporting group title

Adalimumab (Week 16 - 28)

Reporting group description

Reporting group title

Placebo then Guselkumab 100 mg (Week 28 - 72)

Reporting group description

Reporting group title

Guselkumab 100 mg (Week 28 - 72)

Reporting group description

Reporting group title

Adalimumab then Guselkumab 100 mg (Week 28 - 72)

Reporting group description

Reporting group title

Adalimumab (After ACP)

Reporting group description

Reporting group title

Guselkumab Combined

Reporting group description

All subjects who received guselkumab 100 mg subcutaneously q8w at Week 76 and thereafter through Week 252.

Reporting group title

Adalimumab then Guselkumab 100 mg (Week 72 - 264)

Reporting group description

All subjects received guselkumab 100 mg at Week 76 and then q8w through Week 252.

Subject analysis set title

Guselkumab Combined

Subject analysis set type

Intention-to-treat

Subject analysis set description

All subjects who crossed over to receive guselkumab 100 mg subcutaneously at Week 16 from placebo group and subjects who were randomized to guselkumab 100 mg group at Week 0. Placebo crossover subjects were included in the guselkumab column after crossover to guselkumab.

Subject analysis set title

Withdrawal Group (Through Week 72)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects in withdrawal group received guselkumab 100 mg SC injection at Weeks 0, 4 and 12 and placebo matched to adalimumab (2 SC injections) at Week 0, followed by placebo matched to adalimumab (1 SC injection) at Weeks 1, 3, 5 and q2w through Week 15 to maintain the blind during PCP. Subjects received placebo matched to guselkumab SC injection at Week 16 then guselkumab 100 mg SC injection at Week 20 and placebo matched to adalimumab (1 SC injection) at q2w from Week 17 through Week 23. These subjects who were PASI 90 responders at Week 28 were randomized to receive placebo matched to guselkumab SC injection at Week 28 and q4w thereafter through Week 72 until loss of >=50% in the improvement in PASI.

Subject analysis set title

Guselkumab Maintenance Group (Through Week 72)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects of maintenance group received guselkumab 100 mg SC injection at Weeks 0, 4 and 12, and placebo matched to adalimumab (2 SC injections) at Week 0 then placebo matched to adalimumab (1 SC injection) at Weeks 1, 3, 5, 7, and q2w through Week 15. Subjects received placebo matched to guselkumab SC injection at Week 16 then guselkumab 100 mg SC injection at Week 20 and placebo matched to adalimumab (1 SC injection) at q2w from Week 17 through Week 23. These subjects were PASI 90 responders who were randomized to receive guselkumab 100 mg SC injection at Week 28 and q8w thereafter through Week 72 and placebo matched to guselkumab SC injection at Weeks 32, 40 and thereafter through Week 72.

Subject analysis set title

Guselkumab 100 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received guselkumab 100 mg SC injection at Weeks 0, 4 and 12, and placebo matched to adalimumab (2 SC injections) at Week 0 then placebo matched to adalimumab (1 SC injection) at Weeks 1, 3, 5 and q2w thereafter through Week 15. Subjects received placebo matched to guselkumab SC injection at Week 16 then guselkumab 100 mg SC injection at Week 20 and placebo matched to adalimumab (1 SC injection) at Weeks 17, 19, 21 and 23.

Subject analysis set title

Adalimumab

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received adalimumab 80 mg (2 SC injections) at Week 0 followed by adalimumab 40 mg (1 SC injection) at Weeks 1, 3, 5 and every other week thereafter through Week 15 and placebo matched to guselkumab SC injection at Weeks 0, 4, and 12. Subjects who received adalimumab in the first period, continued to receive adalimumab 40 mg (1 SC injection) q2w from Week 17 through Week 23 and placebo matched to guselkumab SC injection at Weeks 16 and 20.

Subject analysis set title

Adalimumab then Guselkumab 100 mg (Week 28 - 264)

Subject analysis set type

Intention-to-treat

Subject analysis set description

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

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End point title

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

End point description

The IGA documents the investigator's assessment of the subject's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The subject's psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). Randomized analysis set included all subjects who were randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 16 or who did not come for evaluation at week 16 were considered nonresponders) was used to impute missing values.

End point type

Primary

End point timeframe

Week 16

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Placebo (Week 0 - 16)	Guselkumab 100 mg (Week 0 - 16)
Number of subjects analysed	248	495
Units: percentage of subjects
number (not applicable)	8.5	84.1

Statistical Analysis 1

Comparison groups

Placebo (Week 0 - 16) v Guselkumab 100 mg (Week 0 - 16)

Number of subjects included in analysis

743

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel chi-square test

Confidence interval

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

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End point title

Percentage of Subjects Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response in the Guselkumab Group Compared to the Placebo Group at Week 16 ^[2]

End point description

The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these area was assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents subjects who achieved at least a 90 percent improvement from baseline in the PASI score. Randomized analysis set included all subjects who were randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 16 or who did not come for evaluation at week 16 were considered nonresponders) was used to impute missing values.

End point type

Primary

End point timeframe

Week 16

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Placebo (Week 0 - 16)	Guselkumab 100 mg (Week 0 - 16)
Number of subjects analysed	248	496
Units: percentage of subjects
number (not applicable)	2.4	70.0

Statistical Analysis 1

Comparison groups

Placebo (Week 0 - 16) v Guselkumab 100 mg (Week 0 - 16)

Number of subjects included in analysis

744

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel chi-square test

Confidence interval

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

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End point title

Percentage of Subjects Who Achieved an IGA Score of Cleared (0) in the Guselkumab Group Compared to the Adalimumab Group at Week 24

End point description

The IGA documents the investigator's assessment of the subject's' psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The subject's psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). Randomized analysis set included all subjects randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 24 or who did not come for evaluation at Week 24 were considered nonresponders) was used to impute missing values.

End point type

Secondary

End point timeframe

Week 24

End point values	Guselkumab 100 mg	Adalimumab
Number of subjects analysed	496	248
Units: percentage of subjects
number (not applicable)	51.8	31.5

Statistical Analysis 1

Comparison groups

Guselkumab 100 mg v Adalimumab

Number of subjects included in analysis

744

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel chi-square test

Confidence interval

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

Top of page

End point title

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

End point description

The IGA documents the investigator's assessment of the subject's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The subject's psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). Randomized analysis set included all subjects randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 24 or who did not come for evaluation at Week 24 were considered nonresponders) was used to impute missing values.

End point type

Secondary

End point timeframe

Week 24

End point values	Guselkumab 100 mg	Adalimumab
Number of subjects analysed	496	248
Units: percentage of subjects
number (not applicable)	83.5	64.9

Statistical Analysis 1

Comparison groups

Guselkumab 100 mg v Adalimumab

Number of subjects included in analysis

744

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel chi-square test

Confidence interval

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

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End point title

Percentage of Subjects Who Achieved PASI 90 Response in the Guselkumab Group Compared to the Adalimumab Group at Week 24

End point description

The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents subjects who achieved at least a 90 percent improvement from baseline in the PASI score. Randomized analysis set. Nonresponder imputation (subjects who met treatment-failure criteria before Week 24 or who did not come for evaluation at Week 24 were considered nonresponders) was used to impute missing values.

End point type

Secondary

End point timeframe

Week 24

End point values	Guselkumab 100 mg	Adalimumab
Number of subjects analysed	496	248
Units: percentage of subjects
number (not applicable)	75.2	54.8

Statistical Analysis 1

Comparison groups

Guselkumab 100 mg v Adalimumab

Number of subjects included in analysis

744

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel chi-square test

Confidence interval

Secondary: Cumulative Maintenance Rate of PASI 90 Response in the Placebo Group Compared to the Guselkumab Group Through Week 48 to Evaluate Loss of a PASI 90 Response

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End point title

Cumulative Maintenance Rate of PASI 90 Response in the Placebo Group Compared to the Guselkumab Group Through Week 48 to Evaluate Loss of a PASI 90 Response

End point description

The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents subjects who achieved at least a 90 percent improvement from baseline in the PASI score. Cumulative maintenance rate was defined as percentage of subjects who maintained their PASI 90 response through Week 48. Randomized analysis set who achieved a PASI 90 response at Week 28, were re-randomized to continue guselkumab or receive placebo and with at least one PASI assessment post Week 28.

End point type

Secondary

End point timeframe

Through Week 48

End point values	Withdrawal Group (Through Week 72)	Guselkumab Maintenance Group (Through Week 72)
Number of subjects analysed	181	193
Units: percentage of subjects
number (not applicable)	35.4	81.8

Statistical Analysis 1

Statistical analysis description

p value is based on the log-rank test stratified by investigator site (pooled).

Comparison groups

Withdrawal Group (Through Week 72) v Guselkumab Maintenance Group (Through Week 72)

Number of subjects included in analysis

374

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logrank

Confidence interval

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

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End point title

Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 16 in the Guselkumab Group Compared to the Placebo Group ^[3]

End point description

The DLQI is a 10-item questionnaire that measures the impact of skin disease on participant's quality of life (QoL). Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on QoL. The DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the subject's life; 2-6 = small effect on the subject's life; 7-12 = moderate effect on the subject's life; 13-18 = very large effect on the subject's life; 19-30 = extremely large effect on the subject's life. Higher scores indicate more impact on QoL of subjects. Randomized analysis set included all subjects who were randomized at Week 0 and with a baseline DLQI score.

End point type

Secondary

End point timeframe

Baseline, Week 16

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Placebo (Week 0 - 16)	Guselkumab 100 mg (Week 0 - 16)
Number of subjects analysed	248	495
Units: units on a scale
arithmetic mean (standard deviation)	-2.6 ( 6.85 )	-11.23 ( 6.82 )

Statistical Analysis 1

Statistical analysis description

p value is based on analysis of variance (ANOVA) model stratified by investigator site (pooled).

Comparison groups

Placebo (Week 0 - 16) v Guselkumab 100 mg (Week 0 - 16)

Number of subjects included in analysis

743

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANOVA

Confidence interval

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

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End point title

Percentage of Subjects Who Achieved an IGA Score of Cleared (0) or Minimal (1) in the Guselkumab Group Compared to the Adalimumab Group at Week 16 ^[4]

End point description

End point type

Secondary

End point timeframe

Week 16

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Guselkumab 100 mg (Week 0 - 16)	Adalimumab (Week 0 - 16)
Number of subjects analysed	496	248
Units: percentage of subjects
number (not applicable)	84.1	67.7

Statistical Analysis 1

Statistical analysis description

p value is based on 1-sided Mantel Haenszel (MH) Z-test adjusted for investigator site (pooled).

Comparison groups

Guselkumab 100 mg (Week 0 - 16) v Adalimumab (Week 0 - 16)

Number of subjects included in analysis

744

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

P-value

< 0.001

Method

MH Z-test

Parameter type

Difference in Percentage

Point estimate

16.4

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

23.2

Notes
[5] - non-inferiority margin= -10.0%

Statistical Analysis 2

Statistical analysis description

p value is based on the Cochran-Mantel-Haenszel chi-square test stratified by investigator site (pooled).

Comparison groups

Guselkumab 100 mg (Week 0 - 16) v Adalimumab (Week 0 - 16)

Number of subjects included in analysis

744

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel chi-square test

Confidence interval

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

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End point title

Percentage of Subjects Who Achieved PASI 90 Response, in the Guselkumab Group Compared to the Adalimumab Group at Week 16 ^[6]

End point description

The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 90 response represents subjects who achieved at least a 90 percent improvement from baseline in the PASI score. Randomized analysis set included all subjects who were randomized at Week 0. Nonresponder imputation (subjects who met treatment-failure criteria before Week 16 or who did not come for evaluation at week 16 were considered nonresponders) was used to impute missing values.

End point type

Secondary

End point timeframe

Week 16

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Guselkumab 100 mg (Week 0 - 16)	Adalimumab (Week 0 - 16)
Number of subjects analysed	495	248
Units: percentage of subjects
number (not applicable)	70.0	46.8

Statistical Analysis 2

Statistical analysis description

p value is based on the Cochran-Mantel-Haenszel chi-square test stratified by investigator site (pooled).

Comparison groups

Guselkumab 100 mg (Week 0 - 16) v Adalimumab (Week 0 - 16)

Number of subjects included in analysis

743

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel chi-square test

Confidence interval

Statistical Analysis 1

Statistical analysis description

p value is based on 1-sided MH Z-test adjusted for investigator site (pooled).

Comparison groups

Guselkumab 100 mg (Week 0 - 16) v Adalimumab (Week 0 - 16)

Number of subjects included in analysis

743

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

P-value

< 0.001

Method

MH Z-test

Parameter type

Difference in Percentage

Point estimate

23.3

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

30.4

Notes
[7] - non-inferiority margin= -10.0%

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

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End point title

Percentage of Subjects Who Achieved PASI 75 Response in the Guselkumab Group Compared to the Adalimumab Group at Week 16 ^[8]

End point description

The PASI is a system used for assessing and grading the severity of psoriatic lesions. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 75 response represents subjects who achieved at least a 75 percent improvement from baseline in the PASI score. Randomized analysis set. Nonresponder imputation (subjects who met treatment-failure criteria before Week 16 or who did not come for evaluation at week 16 were considered nonresponders) was used to impute missing values.

End point type

Secondary

End point timeframe

Week 16

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Guselkumab 100 mg (Week 0 - 16)	Adalimumab (Week 0 - 16)
Number of subjects analysed	496	248
Units: percentage of subjects
number (not applicable)	86.3	68.5

Statistical Analysis 2

Statistical analysis description

p value is based on the Cochran-Mantel-Haenszel chi-square test stratified by investigator site (pooled).

Comparison groups

Guselkumab 100 mg (Week 0 - 16) v Adalimumab (Week 0 - 16)

Number of subjects included in analysis

744

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel chi-square test

Confidence interval

Statistical Analysis 1

Statistical analysis description

p value is based on 1-sided MH Z-test adjusted for investigator site (pooled).

Comparison groups

Guselkumab 100 mg (Week 0 - 16) v Adalimumab (Week 0 - 16)

Number of subjects included in analysis

744

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

P-value

< 0.001

Method

MH Z-test

Parameter type

Difference in percentage

Point estimate

17.7

Confidence interval

level

95%

sides

2-sided

lower limit

11.4

upper limit

24.4

Notes
[9] - non-inferiority margin= -10%

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

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End point title

Percentage of Subjects who Achieved a Scalp-specific Investigator's Global Assessment (ss-IGA) Score of 0 or 1 and at Least a 2-Grade Improvement From Baseline at Week 16 in the Guselkumab Group Compared to the Placebo Group ^[10]

End point description

The ss-IGA instrument is used to evaluate the disease severity of scalp psoriasis. The lesions were assessed in terms of the clinical signs of redness, thickness, and scaliness, which are scored on a 5-point scale ranging from 0 = absence of disease, 1 = very mild disease, 2 = mild disease, 3 = moderate disease, and 4 = severe disease. Population analyzed included only randomized subjects who had an ss-IGA score greater than or equal to (>=) 2 at baseline. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint.

End point type

Secondary

End point timeframe

Week 16

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Placebo (Week 0 - 16)	Guselkumab 100 mg (Week 0 - 16)
Number of subjects analysed	202	408
Units: percentage of subjects
number (not applicable)	10.9	80.6

Statistical Analysis 1

Statistical analysis description

p value is based on the Cochran-Mantel-Haenszel chi-square test stratified by investigator site (pooled).

Comparison groups

Placebo (Week 0 - 16) v Guselkumab 100 mg (Week 0 - 16)

Number of subjects included in analysis

610

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel chi-square test

Confidence interval

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

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End point title

Change From Baseline in Psoriasis Symptom and Sign Diary (PSSD) Symptom Score at Week 16 in the Guselkumab Group Compared to the Placebo Group ^[11]

End point description

The PSSD consisted of 11 items covering symptoms (itch, pain, stinging, burning, and skin tightness) and patient-observable signs (skin dryness, cracking, scaling, shedding or flaking, redness, and bleeding) using 0 (absent) to 10 (worst imaginable) numerical rating scales for severity. The average value is converted into 0-100 scoring, such that Symptom [or Sign] score=average value*10, where, 0=least severe and 100=most severe and higher score indicates more severe disease. PSSD analysis set included all subjects who had baseline PSSD scores as the average score of at least 4 days out of the 7 days prior to the Week 0 visit. This endpoint was planned to be compared only for groups Placebo and Guselkumab 100 mg.

End point type

Secondary

End point timeframe

Baseline and Week 16

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Placebo (Week 0 - 16)	Guselkumab 100 mg (Week 0 - 16)
Number of subjects analysed	198	411
Units: units on a scale
arithmetic mean (standard deviation)	-8.3 ( 23.67 )	-40.4 ( 26.52 )

Statistical Analysis 1

Statistical analysis description

p value is based on ANOVA model stratified by investigator site (pooled).

Comparison groups

Placebo (Week 0 - 16) v Guselkumab 100 mg (Week 0 - 16)

Number of subjects included in analysis

609

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANOVA

Confidence interval

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

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End point title

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

End point description

The PSSD consisted of 11 items covering symptoms (itch, pain, stinging, burning, and skin tightness) and patient-observable signs (skin dryness, cracking, scaling, shedding or flaking, redness, and bleeding) using 0 (absent) to 10 (worst imaginable) numerical rating scales for severity. The average value is converted into 0-100 scoring, such that Symptom [or Sign] score=average value*10, where, 0=least severe and 100=most severe and higher score indicates more severe disease. PSSD analysis set included all subjects who were randomized at Week 0 and had baseline PSSD score greater than 0. This endpoint was planned to be compared only for groups Placebo and Guselkumab 100 mg.

End point type

Secondary

End point timeframe

Week 24

End point values	Guselkumab 100 mg	Adalimumab
Number of subjects analysed	410	200
Units: percentage of subjects
number (not applicable)	35.1	22.5

Statistical Analysis 1

Statistical analysis description

p value is based on the Cochran-Mantel-Haenszel chi-square test stratified by investigator site (pooled).

Comparison groups

Guselkumab 100 mg v Adalimumab

Number of subjects included in analysis

610

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Cochran-Mantel-Haenszel chi-square test

Confidence interval

Secondary: Cumulative Maintenance Rate of PASI 90 Response in the Guselkumab Withdrawal Group Compared to the Guselkumab Maintenance Group Through Week 72 to Evaluate Loss of a PASI 90 Response

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End point title

Cumulative Maintenance Rate of PASI 90 Response in the Guselkumab Withdrawal Group Compared to the Guselkumab Maintenance Group Through Week 72 to Evaluate Loss of a PASI 90 Response

End point description

In PASI system, body is divided into 4 regions: head, trunk, upper and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score ranging from 0 to 6 and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. PASI produces a numeric score ranging from 0 to 72. Higher score=more severe disease. PASI 90 response represents subjects who achieved at least a 90 percent improvement from baseline in PASI score. Cumulative maintenance rate was determined for subjects who were withdrawn from study medication and who maintained guselkumab every 8 weeks dosing schedule and was defined as percentage of subjects who maintained their PASI 90 response through Week 72. Population analyzed included PASI 90 responders at Week 28 and who were randomized at Week 28 and treated with guselkumab. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint.

End point type

Secondary

End point timeframe

Through Week 72

End point values	Withdrawal Group (Through Week 72)	Guselkumab Maintenance Group (Through Week 72)
Number of subjects analysed	181	193
Units: percentage of subjects
number (not applicable)	11.5	86

No statistical analyses for this end point

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

Top of page

End point title

Percentage of Subjects Who Achieved PASI 90 Response at Week 252

End point description

In PASI system, body is divided into 4 regions: head, trunk, upper and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score ranging from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. PASI produces a numeric score that can range from 0 to 72. Higher score= more severe disease. PASI 90 response signify subjects who achieved at least a 90 percent improvement from baseline in the PASI score. Population analyzed included subjects who were randomized at Week 0 and treated with guselkumab. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.

End point type

Secondary

End point timeframe

Week 252

End point values	Guselkumab Combined	Adalimumab then Guselkumab 100 mg (Week 28 - 264)
Number of subjects analysed	560	177
Units: percentage of subjects
number (not applicable)	82.0	79.1

No statistical analyses for this end point

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

Top of page

End point title

Percentage of Subjects Who Achieved PASI 75 Response at Week 252

End point description

In PASI system, body is divided into 4 regions: head, trunk, upper and lower extremities. Each of these areas were assessed separately for the percentage of the area involved, which translates to a numeric score ranging from 0 to 6, and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4. PASI produces a numeric score that can range from 0 to 72. Higher score= more severe disease. PASI 75 response signify subjects who achieved at least a 75 percent improvement from baseline in the PASI score. Population analyzed included subjects who were randomized at Week 0 and treated with guselkumab. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.

End point type

Secondary

End point timeframe

Week 252

End point values	Guselkumab Combined	Adalimumab then Guselkumab 100 mg (Week 28 - 264)
Number of subjects analysed	560	177
Units: percentage of subjects
number (not applicable)	93.4	92.7

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

The IGA documents the investigator's assessment of the subject's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The subject’s psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). Population analyzed included subjects who were randomized at Week 0 and treated with guselkumab. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.

End point type

Secondary

End point timeframe

Week 252

End point values	Guselkumab Combined	Adalimumab then Guselkumab 100 mg (Week 28 - 264)
Number of subjects analysed	559	177
Units: percentage of subjects
number (not applicable)	85.0	83.1

No statistical analyses for this end point

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

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End point title

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

End point description

DLQI measures impact of skin disease on subject's QoL. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much). DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1=no effect on subject's life; 2-6=small effect; 7-12=moderate effect; 13-18=very large effect; 19-30=extremely large effect. DLQI was calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. Higher scores indicate more impact on subject's QoL. Population analyzed included subjects randomized at Week 0 and treated with guselkumab with baseline DLQI score >1. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.

End point type

Secondary

End point timeframe

Week 252

End point values	Guselkumab Combined	Adalimumab then Guselkumab 100 mg (Week 28 - 264)
Number of subjects analysed	550	173
Units: percentage of subjects
number (not applicable)	71.1	69.9

No statistical analyses for this end point

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

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End point title

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

End point description

The PSSD consisted of 11 items covering symptoms (itch, pain, stinging, burning, and skin tightness) and patient-observable signs (skin dryness, cracking, scaling, shedding or flaking, redness, and bleeding) using 0 (absent) to 10 (worst imaginable) numerical rating scales for severity. The average value is converted into 0-100 scoring, such that Symptom score=average value*10, where, 0=least severe and 100=most severe and higher score indicates more severe disease. Population analyzed included subjects who were randomized at Week 0 and treated with guselkumab with baseline PSSD symptom score >0. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.

End point type

Secondary

End point timeframe

Week 252

End point values	Guselkumab Combined	Adalimumab then Guselkumab 100 mg (Week 28 - 264)
Number of subjects analysed	460	145
Units: percentage of subjects
number (not applicable)	42.0	36.6

No statistical analyses for this end point

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

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End point title

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

End point description

The PSSD consisted of 11 items covering symptoms (itch, pain, stinging, burning, and skin tightness) and patient-observable signs (skin dryness, cracking, scaling, shedding or flaking, redness, and bleeding) using 0 (absent) to 10 (worst imaginable) numerical rating scales for severity. The average value is converted into 0-100 scoring, such that Sign score=average value*10, where, 0=least severe and 100=most severe and higher score indicates more severe disease. Population analyzed included subjects who were randomized at Week 0 and treated with guselkumab with baseline PSSD sign score >0. The analysis was performed using observed data after applying treatment failure rules. Here, N (Number of subjects analyzed) signifies subjects who were analyzed for this endpoint. As per planned analysis, subjects from the baseline guselkumab group and the placebo crossover group were combined into a single guselkumab group for assessment of this endpoint.

End point type

Secondary

End point timeframe

Week 252

End point values	Guselkumab Combined	Adalimumab then Guselkumab 100 mg (Week 28 - 264)
Number of subjects analysed	461	145
Units: percentage of subjects
number (not applicable)	31.0	24.1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline (Week 0) up to Week 264

Adverse event reporting additional description

All subjects who were randomized at Week 0, received >=1 dose of study agent (partial or complete). Subjects who discontinued treatment prematurely were followed for at least 12 weeks after last dose and who discontinued in the previous period and had safety follow-up continuing in the current period, were counted in both the periods.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Guselkumab 100 mg (Week 0 - 16)

Reporting group description

Reporting group title

Placebo (Week 0 - 16)

Reporting group description

Subjects received placebo matched to guselkumab SC injection at Weeks 0, 4, and 12 and placebo matched to adalimumab (2 SC injections) at Week 0, followed by placebo matched to adalimumab (1 SC injection) at Week 1 and every other week thereafter through Week 15 to maintain the blind during placebo controlled period (PCP).

Reporting group title

Placebo then Guselkumab 100 mg (Week 16 - 28)

Reporting group description

Reporting group title

Adalimumab (Week 0 - 16)

Reporting group description

Reporting group title

Guselkumab 100 mg (Week 16 - 28)

Reporting group description

Reporting group title

Adalimumab (Week 16 - 28)

Reporting group description

Reporting group title

Placebo then Guselkumab 100 mg (Week 28 - 264)

Reporting group description

Subjects assigned to the placebo, then guselkumab arm through Week 28 were assessed for PASI 90 response at Week 28. Subjects who were PASI 90 non-responders received guselkumab 100 mg SC injection at Week 28 and then every 8 weeks (q8w) thereafter through Week 72 and placebo matched to guselkumab SC injection at Week 32 and then q8w through Week 72. Subjects who were PASI 90 responders at Week 28 received placebo matched to guselkumab SC injection at Week 28 and every 4 weeks (q4w) thereafter through Week 72 or until loss of greater than or equal to (>=) 50 percentage (%) in the improvement in PASI (Withdrawal and retreatment period). If they lost response according to this definition, they were retreated with guselkumab. Thereafter, subjects received guselkumab 100 mg at Week 76 and then q8w through Week 252.

Reporting group title

Guselkumab 100 mg (Week 28 - 264)

Reporting group description

Reporting group title

Adalimumab Then Guselkumab 100 mg (Week 28 - 264)

Reporting group description

Subjects who were assigned to the adalimumab arm through Week 28 were assessed for PASI 90 response at Week 28. Subjects who were PASI 90 non-responders received guselkumab 100 mg SC injection at Week 28 and 32 and q8w thereafter through Week 72 and placebo matched to guselkumab SC injection at Week 36 and q8w through Week 72. Subjects who were PASI 90 responders, received placebo matched to guselkumab SC injection q4w thereafter through Week 72 or until loss of >=50% in the improvement in PASI. If they lost response according to this definition, they were treated with guselkumab. Thereafter, subjects received guselkumab 100 mg at Week 76 and then q8w through Week 252. The presentation of data from the adalimumab group from Week 28 to Week 264 is divided into 2 arms (adalimumab then guselkumab 100 mg (Week 28 - 264) and adalimumab (After ACP) in order to represent exposure to 2 different active study agents (adalimumab vs guselkumab).

Reporting group title

Adalimumab (After ACP)

Reporting group description

Serious adverse events	Guselkumab 100 mg (Week 0 - 16)	Placebo (Week 0 - 16)	Placebo then Guselkumab 100 mg (Week 16 - 28)	Adalimumab (Week 0 - 16)	Guselkumab 100 mg (Week 16 - 28)	Adalimumab (Week 16 - 28)	Placebo then Guselkumab 100 mg (Week 28 - 264)	Guselkumab 100 mg (Week 28 - 264)	Adalimumab Then Guselkumab 100 mg (Week 28 - 264)	Adalimumab (After ACP)
Total subjects affected by serious adverse events
subjects affected / exposed	8 / 494 (1.62%)	3 / 248 (1.21%)	5 / 233 (2.15%)	6 / 248 (2.42%)	10 / 481 (2.08%)	3 / 240 (1.25%)	36 / 229 (15.72%)	66 / 473 (13.95%)	36 / 220 (16.36%)	1 / 11 (9.09%)
number of deaths (all causes)	0	1	1	3	0	3	1	0	3	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-Cell Lymphoma
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Benign Neoplasm of Thyroid Gland
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Breast Cancer
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	2 / 229 (0.87%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchial Carcinoma
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Endometrial Cancer
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ependymoma
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fibroadenoma of Breast
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inflammatory Pseudotumour
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lipoma
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	1 / 233 (0.43%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant Melanoma
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteochondroma
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic Carcinoma Stage Iv
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostate Cancer
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	1 / 481 (0.21%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal Cancer
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinonasal Papilloma
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine Leiomyoma
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Haematoma
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	2 / 229 (0.87%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Varicose Vein
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ectopic Pregnancy
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Non-Cardiac Chest Pain
subjects affected / exposed	1 / 494 (0.20%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sudden Death
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Immune system disorders
Anaphylactic Reaction
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Drug Hypersensitivity
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	1 / 233 (0.43%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Social circumstances
Miscarriage of Partner
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Benign Prostatic Hyperplasia
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian Cyst
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	1 / 481 (0.21%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostatitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine Haemorrhage
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Nasal Septum Deviation
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	2 / 473 (0.42%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary Embolism
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary Fibrosis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory Failure
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinus Polyp
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sleep Apnoea Syndrome
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Device Dislocation
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Alcoholism
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anxiety
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide Attempt
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	1 / 248 (0.40%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	1 / 494 (0.20%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Chest Injury
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	1 / 233 (0.43%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Craniocerebral Injury
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye Injury
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Femur Fracture
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Head Injury
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Joint Dislocation
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ligament Rupture
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ligament Sprain
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower Limb Fracture
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus Injury
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Multiple Fractures
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	1 / 233 (0.43%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Multiple Injuries
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nerve Injury
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radius Fracture
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal Cord Injury Cervical
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subdural Haematoma
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subdural Haemorrhage
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	1 / 233 (0.43%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ulnar Nerve Injury
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	1 / 233 (0.43%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute Myocardial Infarction
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	1 / 481 (0.21%)	0 / 240 (0.00%)	2 / 229 (0.87%)	4 / 473 (0.85%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2	1 / 4	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina Pectoris
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	1 / 248 (0.40%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	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	0 / 0	0 / 0	0 / 0	0 / 0
Angina Unstable
subjects affected / exposed	1 / 494 (0.20%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial Fibrillation
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac Failure
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	1 / 481 (0.21%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary Artery Disease
subjects affected / exposed	1 / 494 (0.20%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial Infarction
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	1 / 248 (0.40%)	1 / 481 (0.21%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	2 / 220 (0.91%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Myocardial Ischaemia
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebellar Stroke
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic Coma
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	1 / 240 (0.42%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myelitis Transverse
subjects affected / exposed	1 / 494 (0.20%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myelopathy
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Paraesthesia
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral Nerve Lesion
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral Nerve Paresis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	1 / 233 (0.43%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	1 / 233 (0.43%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	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	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	1 / 481 (0.21%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Retinal Vein Occlusion
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Duodenal Perforation
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	1 / 248 (0.40%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal Haemorrhage
subjects affected / exposed	0 / 494 (0.00%)	1 / 248 (0.40%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoidal Haemorrhage
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal Hernia
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	1 / 248 (0.40%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	2 / 473 (0.42%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Irritable Bowel Syndrome
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mallory-Weiss Syndrome
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	1 / 481 (0.21%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis Acute
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Submaxillary Gland Enlargement
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Umbilical Hernia
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper Gastrointestinal Haemorrhage
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis Acute
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	2 / 220 (0.91%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis Chronic
subjects affected / exposed	0 / 494 (0.00%)	1 / 248 (0.40%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	2 / 473 (0.42%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	2 / 220 (0.91%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic Steatosis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	1 / 481 (0.21%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal Colic
subjects affected / exposed	1 / 494 (0.20%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ureterolithiasis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary Retention
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral Disc Protrusion
subjects affected / exposed	1 / 494 (0.20%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscular Weakness
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal Chest Pain
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal Pain
subjects affected / exposed	0 / 494 (0.00%)	1 / 248 (0.40%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	2 / 473 (0.42%)	3 / 220 (1.36%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psoriatic Arthropathy
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	1 / 248 (0.40%)	0 / 481 (0.00%)	1 / 240 (0.42%)	1 / 229 (0.44%)	3 / 473 (0.63%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	1 / 1	0 / 1	0 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rotator Cuff Syndrome
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Synovitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	2 / 229 (0.87%)	4 / 473 (0.85%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis Perforated
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	1 / 481 (0.21%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	1 / 11 (9.09%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	4 / 473 (0.85%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	3 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic Sinusitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic Tonsillitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Disseminated Tuberculosis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	1 / 248 (0.40%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	1 / 494 (0.20%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hiv Infection
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injection Site Abscess
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	1 / 248 (0.40%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritonsillar Abscess
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pilonidal Cyst
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	1 / 229 (0.44%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	2 / 229 (0.87%)	2 / 473 (0.42%)	2 / 220 (0.91%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	1 / 2	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Retroperitoneal Abscess
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	1 / 220 (0.45%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Soft Tissue Infection
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	1 / 481 (0.21%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tuberculosis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	1 / 240 (0.42%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper Respiratory Tract Infection
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vestibular Neuronitis
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound Infection
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	1 / 233 (0.43%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Obesity
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	1 / 473 (0.21%)	0 / 220 (0.00%)	0 / 11 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Guselkumab 100 mg (Week 0 - 16)	Placebo (Week 0 - 16)	Placebo then Guselkumab 100 mg (Week 16 - 28)	Adalimumab (Week 0 - 16)	Guselkumab 100 mg (Week 16 - 28)	Adalimumab (Week 16 - 28)	Placebo then Guselkumab 100 mg (Week 28 - 264)	Guselkumab 100 mg (Week 28 - 264)	Adalimumab Then Guselkumab 100 mg (Week 28 - 264)	Adalimumab (After ACP)
Total subjects affected by non serious adverse events
subjects affected / exposed	125 / 494 (25.30%)	60 / 248 (24.19%)	33 / 233 (14.16%)	51 / 248 (20.56%)	63 / 481 (13.10%)	45 / 240 (18.75%)	144 / 229 (62.88%)	297 / 473 (62.79%)	159 / 220 (72.27%)	4 / 11 (36.36%)
Vascular disorders
Hypertension
subjects affected / exposed	10 / 494 (2.02%)	4 / 248 (1.61%)	1 / 233 (0.43%)	6 / 248 (2.42%)	4 / 481 (0.83%)	1 / 240 (0.42%)	27 / 229 (11.79%)	43 / 473 (9.09%)	20 / 220 (9.09%)	0 / 11 (0.00%)
occurrences all number	11	4	1	6	4	1	30	51	23	0
Cardiac disorders
Cardiac Failure Congestive
subjects affected / exposed	0 / 494 (0.00%)	0 / 248 (0.00%)	0 / 233 (0.00%)	0 / 248 (0.00%)	0 / 481 (0.00%)	0 / 240 (0.00%)	0 / 229 (0.00%)	0 / 473 (0.00%)	0 / 220 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Nervous system disorders
Headache
subjects affected / exposed	25 / 494 (5.06%)	7 / 248 (2.82%)	5 / 233 (2.15%)	5 / 248 (2.02%)	6 / 481 (1.25%)	4 / 240 (1.67%)	9 / 229 (3.93%)	31 / 473 (6.55%)	17 / 220 (7.73%)	0 / 11 (0.00%)
occurrences all number	27	7	5	6	6	4	18	44	25	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	11 / 494 (2.23%)	2 / 248 (0.81%)	0 / 233 (0.00%)	4 / 248 (1.61%)	3 / 481 (0.62%)	3 / 240 (1.25%)	11 / 229 (4.80%)	15 / 473 (3.17%)	12 / 220 (5.45%)	0 / 11 (0.00%)
occurrences all number	12	2	0	4	3	3	13	16	14	0
Gastrooesophageal Reflux Disease
subjects affected / exposed	1 / 494 (0.20%)	0 / 248 (0.00%)	0 / 233 (0.00%)	1 / 248 (0.40%)	1 / 481 (0.21%)	2 / 240 (0.83%)	2 / 229 (0.87%)	12 / 473 (2.54%)	4 / 220 (1.82%)	1 / 11 (9.09%)
occurrences all number	1	0	0	1	1	2	2	13	7	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	8 / 494 (1.62%)	4 / 248 (1.61%)	1 / 233 (0.43%)	1 / 248 (0.40%)	2 / 481 (0.42%)	2 / 240 (0.83%)	10 / 229 (4.37%)	16 / 473 (3.38%)	13 / 220 (5.91%)	1 / 11 (9.09%)
occurrences all number	8	4	1	1	2	2	12	22	16	1
Skin and subcutaneous tissue disorders
Dermatitis Contact
subjects affected / exposed	4 / 494 (0.81%)	2 / 248 (0.81%)	0 / 233 (0.00%)	1 / 248 (0.40%)	2 / 481 (0.42%)	0 / 240 (0.00%)	2 / 229 (0.87%)	11 / 473 (2.33%)	6 / 220 (2.73%)	1 / 11 (9.09%)
occurrences all number	4	2	0	1	2	0	2	14	6	1
Psoriasis
subjects affected / exposed	1 / 494 (0.20%)	3 / 248 (1.21%)	0 / 233 (0.00%)	5 / 248 (2.02%)	1 / 481 (0.21%)	1 / 240 (0.42%)	3 / 229 (1.31%)	8 / 473 (1.69%)	9 / 220 (4.09%)	1 / 11 (9.09%)
occurrences all number	1	3	0	6	1	1	3	10	9	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	11 / 494 (2.23%)	6 / 248 (2.42%)	0 / 233 (0.00%)	2 / 248 (0.81%)	8 / 481 (1.66%)	6 / 240 (2.50%)	17 / 229 (7.42%)	46 / 473 (9.73%)	22 / 220 (10.00%)	0 / 11 (0.00%)
occurrences all number	12	6	0	2	8	7	36	56	32	0
Back Pain
subjects affected / exposed	4 / 494 (0.81%)	6 / 248 (2.42%)	0 / 233 (0.00%)	0 / 248 (0.00%)	6 / 481 (1.25%)	0 / 240 (0.00%)	18 / 229 (7.86%)	25 / 473 (5.29%)	16 / 220 (7.27%)	1 / 11 (9.09%)
occurrences all number	4	6	0	0	7	0	26	32	16	1
Infections and infestations
Bronchitis
subjects affected / exposed	3 / 494 (0.61%)	3 / 248 (1.21%)	6 / 233 (2.58%)	5 / 248 (2.02%)	3 / 481 (0.62%)	3 / 240 (1.25%)	15 / 229 (6.55%)	23 / 473 (4.86%)	21 / 220 (9.55%)	0 / 11 (0.00%)
occurrences all number	3	3	7	6	3	3	16	28	23	0
Gastroenteritis
subjects affected / exposed	4 / 494 (0.81%)	1 / 248 (0.40%)	0 / 233 (0.00%)	5 / 248 (2.02%)	1 / 481 (0.21%)	0 / 240 (0.00%)	11 / 229 (4.80%)	16 / 473 (3.38%)	11 / 220 (5.00%)	0 / 11 (0.00%)
occurrences all number	4	1	0	5	1	0	12	18	13	0
Nasopharyngitis
subjects affected / exposed	35 / 494 (7.09%)	16 / 248 (6.45%)	12 / 233 (5.15%)	20 / 248 (8.06%)	18 / 481 (3.74%)	16 / 240 (6.67%)	67 / 229 (29.26%)	142 / 473 (30.02%)	81 / 220 (36.82%)	0 / 11 (0.00%)
occurrences all number	36	17	12	20	19	17	160	296	175	0
Pharyngitis
subjects affected / exposed	7 / 494 (1.42%)	2 / 248 (0.81%)	2 / 233 (0.86%)	1 / 248 (0.40%)	5 / 481 (1.04%)	2 / 240 (0.83%)	18 / 229 (7.86%)	32 / 473 (6.77%)	5 / 220 (2.27%)	0 / 11 (0.00%)
occurrences all number	7	2	2	1	5	2	23	43	9	0
Sinusitis
subjects affected / exposed	3 / 494 (0.61%)	3 / 248 (1.21%)	1 / 233 (0.43%)	2 / 248 (0.81%)	3 / 481 (0.62%)	2 / 240 (0.83%)	16 / 229 (6.99%)	23 / 473 (4.86%)	11 / 220 (5.00%)	0 / 11 (0.00%)
occurrences all number	3	3	1	3	3	2	20	32	16	0
Upper Respiratory Tract Infection
subjects affected / exposed	16 / 494 (3.24%)	10 / 248 (4.03%)	5 / 233 (2.15%)	4 / 248 (1.61%)	12 / 481 (2.49%)	6 / 240 (2.50%)	39 / 229 (17.03%)	111 / 473 (23.47%)	49 / 220 (22.27%)	1 / 11 (9.09%)
occurrences all number	17	11	5	5	13	7	68	213	110	1
Viral Upper Respiratory Tract Infection
subjects affected / exposed	6 / 494 (1.21%)	1 / 248 (0.40%)	1 / 233 (0.43%)	0 / 248 (0.00%)	0 / 481 (0.00%)	1 / 240 (0.42%)	7 / 229 (3.06%)	19 / 473 (4.02%)	12 / 220 (5.45%)	0 / 11 (0.00%)
occurrences all number	7	1	1	0	0	1	13	26	15	0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	2 / 494 (0.40%)	1 / 248 (0.40%)	0 / 233 (0.00%)	1 / 248 (0.40%)	0 / 481 (0.00%)	2 / 240 (0.83%)	4 / 229 (1.75%)	9 / 473 (1.90%)	3 / 220 (1.36%)	1 / 11 (9.09%)
occurrences all number	2	1	0	1	0	2	5	13	3	2

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Were there any global substantial amendments to the protocol? Yes

12 Feb 2015

Amendment 1 included the following major changes: assessments describing antibodies to study agent were added at Week 16 and Week 44; A physical examination and weight measurement were moved to Week 100 from Week 108, and added at Week 148; The inclusion criteria were clarified to indicate that barrier methods should be used with a spermicidal agent if spermicidal agents were available in their locale; The exclusion criterion for major surgery was clarified. The text describing serious adverse event (SAE) reporting for hospitalization was edited to address a potential contradiction with this exclusion criterion; and an exclusion criterion was added to exclude sponsor employees from participation in the study.

25 Jun 2015

Amendnment 2 included the following change: to restrict the use of concomitant medications for psoriasis through Week 76 instead of through Week 48.

04 Apr 2017

Amendment 3 included the following major changes: to extend the duration of long-term extensions by 2 years thereby changing the final study visit (end of study) from Week 160 to Week 264; Updated all references to end of study and last study visit throughout the protocol; Updated to capture that, after Week 148, study drug administration information was no longer captured electronically in an eDiary, but were documented in source documents and the electronic case report form (eCRF); and minor errors were noted.

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.

All subjects were on guselkumab after Week 76; therefore, there was no concurrent control group within the study after Week 76.

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Clinical trials

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

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

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

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

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

Secondary: Cumulative Maintenance Rate of PASI 90 Response in the Placebo Group Compared to the Guselkumab Group Through Week 48 to Evaluate Loss of a PASI 90 Response

Secondary: Cumulative Maintenance Rate of PASI 90 Response in the Placebo Group Compared to the Guselkumab Group Through Week 48 to Evaluate Loss of a PASI 90 Response

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Cumulative Maintenance Rate of PASI 90 Response in the Guselkumab Withdrawal Group Compared to the Guselkumab Maintenance Group Through Week 72 to Evaluate Loss of a PASI 90 Response

Secondary: Cumulative Maintenance Rate of PASI 90 Response in the Guselkumab Withdrawal Group Compared to the Guselkumab Maintenance Group Through Week 72 to Evaluate Loss of a PASI 90 Response

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

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

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

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

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

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

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

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

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

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

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

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

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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