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Clinical Trial Results:
A Phase 3 Randomised, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel Group, Multi-Center Study Investigating the Efficacy and Safety of PF-04965842 and Dupilumab in Comparison with Placebo in Adult Subjects on Background Topical Therapy, With Moderate to Severe Atopic Dermatitis

Summary
EudraCT number	2018-002573-21
Trial protocol	SK BG CZ LV FR HU AT GB ES IT
Global end of trial date	06 Mar 2020

Results information
Results version number	v1(current)
This version publication date	12 Mar 2021
First version publication date	12 Mar 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

B7451029

ISRCTN number

US NCT number

NCT03720470

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

28 May 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

06 Mar 2020

Was the trial ended prematurely?

Main objective of the trial

To compare the efficacy of 100 milligram (mg) and 200 mg once daily (QD) of PF-04965842 versus placebo in adult subjects on background topical therapy with moderate to severe atopic dermatitis.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

29 Oct 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 38

Country: Number of subjects enrolled

Bulgaria: 16

Country: Number of subjects enrolled

Canada: 36

Country: Number of subjects enrolled

Chile: 30

Country: Number of subjects enrolled

Czechia: 55

Country: Number of subjects enrolled

Germany: 55

Country: Number of subjects enrolled

Hungary: 15

Country: Number of subjects enrolled

Italy: 3

Country: Number of subjects enrolled

Japan: 76

Country: Number of subjects enrolled

Korea, Republic of: 33

Country: Number of subjects enrolled

Latvia: 9

Country: Number of subjects enrolled

Mexico: 13

Country: Number of subjects enrolled

Poland: 182

Country: Number of subjects enrolled

Slovakia: 15

Country: Number of subjects enrolled

Spain: 6

Country: Number of subjects enrolled

Taiwan: 16

Country: Number of subjects enrolled

United Kingdom: 67

Country: Number of subjects enrolled

United States: 172

Worldwide total number of subjects

837

EEA total number of subjects

356

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)

783

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

The study had treatment period of 20 weeks. The first part of this treatment period consists of a 16-week period where subjects received PF-04965842, dupilumab and placebo. The randomisation and double-blind was maintained during the final 4 weeks of the treatment period, but subjects only received PF-04965842 and placebo.

Period 1 title

Treatment Period: First Part 16 Weeks

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo up to Week (Wk)16

Arm description

Subjects were randomised to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received oral placebo matched to PF-04965842 once daily every other week from Day 1 till Week 16.

PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20

Arm description

Subjects were randomised to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, followed by administration of PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20.

Arm type

Experimental

Investigational medicinal product name

Abrocitinib100 mg+Placebo Inj.

Investigational medicinal product code

PF-04965842

Other name

Pharmaceutical forms

Tablet, Injection

Routes of administration

Oral use, Subcutaneous use

Dosage and administration details

Subjects were received PF-04965842 100 mg tablet with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16.

PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20

Arm description

Subjects were randomised to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, followed by administration of PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20.

Arm type

Experimental

Investigational medicinal product name

Abrocitinib 200 mg+Placebo Inj.

Investigational medicinal product code

PF-04965842

Other name

Pharmaceutical forms

Tablet, Injection

Routes of administration

Oral use, Subcutaneous use

Dosage and administration details

Subjects received PF-04965842 200 mg tablet with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16.

Dupilumab 300mg+Oral Placebo up to Wk16>Oral Placebo Wk 16-20

Arm description

Subjects were randomised to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, followed by administration of oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20.

Arm type

Experimental

Investigational medicinal product name

Dupilumab 300mg+ Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet, Injection

Routes of administration

Oral use, Subcutaneous use

Dosage and administration details

Subjects received dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16.

Number of subjects in period 1	Placebo up to Week (Wk)16	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk16>Oral Placebo Wk 16-20
Started	131	238	226	242
Full Analysis Set	131	238	226	242
Completed	117	217	208	223
Not completed	14	21	18	19
Consent withdrawn by subject	5	9	3	6
Adverse event, non-fatal	5	5	8	6
Protocol deviation	2	2	2	1
Pregnancy	-	-	1	1
Unspecified	1	1	2	2
Medication Error Without Associated Adverse Event	-	1	1	-
Lost to follow-up	1	2	1	2
Lack of efficacy	-	1	-	1

Period 2 title

Treatment Period: Final 4 Weeks

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20

Arm description

Subjects who were randomised to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20.

Arm type

Experimental

Investigational medicinal product name

Abrocitinib 100 mg

Investigational medicinal product code

PF-04965842

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20.

Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20

Arm description

Subjects who were randomised to receive oral placebo matched to PF-04965842 with subcutaneous injectable placebo matched to dupilumab till Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20.

Arm type

Experimental

Investigational medicinal product name

Abrocitinib 200 mg

Investigational medicinal product code

PF-04965842

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20.

PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20

Arm description

Arm type

Experimental

Investigational medicinal product name

Abrocitinib 100mg

Investigational medicinal product code

PF-04965842

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received of PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20.

PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20

Arm description

Arm type

Experimental

Investigational medicinal product name

Abrocitinib 200 mg

Investigational medicinal product code

PF-04965842

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20.

Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20

Arm description

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20.

Number of subjects in period 2	Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20	Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20
Started	60	57	217	208	223
Treated/ Safety Analysis Set	60	57	217	208	223
Full Analysis Set	60	57	217	208	223
Completed	58	55	210	204	218
Not completed	2	2	7	4	5
Consent withdrawn by subject	1	-	2	2	2
Adverse event, non-fatal	-	-	2	1	1
Protocol deviation	-	1	-	-	-
Pregnancy	-	-	-	-	1
Unspecified	1	-	2	1	-
Lost to follow-up	-	-	1	-	1
Lack of efficacy	-	1	-	-	-

Baseline characteristics

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Reporting group title

Placebo up to Week (Wk)16

Reporting group description

Subjects were randomised to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16.

Reporting group title

PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20

Reporting group description

Reporting group title

PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20

Reporting group description

Reporting group title

Dupilumab 300mg+Oral Placebo up to Wk16>Oral Placebo Wk 16-20

Reporting group description

Reporting group values	Placebo up to Week (Wk)16	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk16>Oral Placebo Wk 16-20	Total
Number of subjects	131	238	226	242	837
Age Categorical
Units: Subjects
<=18 years	0	0	0	0	0
Between 18 and 65 years	121	224	211	227	783
>=65 years	10	14	15	15	54
Sex: Female, Male
Units: Subjects
Female	54	118	122	134	428
Male	77	120	104	108	409
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	2	1	0	2	5
Asian	31	48	53	46	178
Native Hawaiian or Other Pacific Islander	1	0	1	0	2
Black or African American	6	6	9	14	35
White	87	182	161	176	606
More than one race	1	1	1	2	5
Unknown or Not Reported	3	0	1	2	6
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	16	35	36	37	124
Not Hispanic or Latino	113	200	187	201	701
Unknown or Not Reported	2	3	3	4	12

End points

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Reporting group title

Placebo up to Week (Wk)16

Reporting group description

Subjects were randomised to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16.

Reporting group title

PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20

Reporting group description

Reporting group title

PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20

Reporting group description

Reporting group title

Dupilumab 300mg+Oral Placebo up to Wk16>Oral Placebo Wk 16-20

Reporting group description

Reporting group title

Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20

Reporting group description

Reporting group title

Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20

Reporting group description

Reporting group title

PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20

Reporting group description

Reporting group title

PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20

Reporting group description

Reporting group title

Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20

Reporting group description

Subject analysis set title

PF-04965842 100 mg + Placebo Injection up to Week 16

Subject analysis set type

Full analysis

Subject analysis set description

Subjects were randomised to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16.

Subject analysis set title

PF-04965842 200 mg + Placebo Injection up to Week 16

Subject analysis set type

Full analysis

Subject analysis set description

Subjects were randomised to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16.

Subject analysis set title

Dupilumab 300 mg + Oral Placebo up to Week 16

Subject analysis set type

Full analysis

Subject analysis set description

Subjects were randomised to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16.

Primary: Percentage of Subjects Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and a Reduction of Greater Than or Equal to (>=) 2 Points From Baseline at Week 12

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End point title

Percentage of Subjects Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and a Reduction of Greater Than or Equal to (>=) 2 Points From Baseline at Week 12 ^[1]

End point description

IGA assessed severity of atopic dermatitis (AD) on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded scalp, palms and sole. FAS analysed till Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Baseline (the last measurement prior to first dosing on Day 1), Week 12

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: Data have been for reported for those arms which were applicable till Week 12.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	129	235	219	241
Units: Percentage of subjects
number (confidence interval 95%)	14.0 (8.0 to 19.9)	36.6 (30.4 to 42.8)	48.4 (41.8 to 55.0)	36.5 (30.4 to 42.6)

PF-04965842 versus placebo

Statistical analysis description

Difference in percentage (PF-04965842 versus placebo) and confidence interval (CI) for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity.

Comparison groups

Placebo up to Week (Wk)16 v PF-04965842 100 mg + Placebo Injection up to Week 16

Number of subjects included in analysis

364

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

23.1

Confidence interval

level

95%

sides

2-sided

lower limit

14.7

upper limit

31.4

PF-04965842 versus placebo

Statistical analysis description

Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity.

Comparison groups

Placebo up to Week (Wk)16 v PF-04965842 200 mg + Placebo Injection up to Week 16

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

34.8

Confidence interval

level

95%

sides

2-sided

lower limit

26.1

upper limit

43.5

Primary: Percentage of Subjects Achieving Eczema Area and Severity Index (EASI) Response >=75 Percent (%) Improvement From Baseline at Week 12

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End point title

Percentage of Subjects Achieving Eczema Area and Severity Index (EASI) Response >=75 Percent (%) Improvement From Baseline at Week 12 ^[2]

End point description

EASI evaluates severity of subjects with AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); (A =EASI area score) ranged from 0.0 to 72.0, higher scores = greater severity of AD. FAS analysed till Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Baseline, Week 12

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: Data have been for reported for those arms which were applicable till Week 12.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	129	235	219	241
Units: Percentage of subjects
number (confidence interval 95%)	27.1 (19.5 to 34.8)	58.7 (52.4 to 65.0)	70.3 (64.3 to 76.4)	58.1 (51.9 to 64.3)

PF-04965842 versus placebo

Statistical analysis description

Comparison groups

Placebo up to Week (Wk)16 v PF-04965842 100 mg + Placebo Injection up to Week 16

Number of subjects included in analysis

364

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

31.9

Confidence interval

level

95%

sides

2-sided

lower limit

22.2

upper limit

41.6

PF-04965842 versus placebo

Statistical analysis description

Comparison groups

Placebo up to Week (Wk)16 v PF-04965842 200 mg + Placebo Injection up to Week 16

Number of subjects included in analysis

348

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

43.2

Confidence interval

level

95%

sides

2-sided

lower limit

33.7

upper limit

52.7

Secondary: Percentage of Subjects With at Least 4 Points Improvement in the Numerical Rating Scale (NRS) for Severity of Pruritus From Baseline at Day 2-15, Week 2, 4, 8, 12 and 16

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End point title

Percentage of Subjects With at Least 4 Points Improvement in the Numerical Rating Scale (NRS) for Severity of Pruritus From Baseline at Day 2-15, Week 2, 4, 8, 12 and 16 ^[3]

End point description

Subjects were asked to assess their worst pruritus/itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst possible itching), where higher scores indicated greater severity. FAS analysed till Week 16. Here, “Number Analyzed” (n) signifies the number of subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and Week 2, 4, 8, 12, 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: Percentage of subjects
number (confidence interval 95%)
Day 2 (n=117, 220, 203, 206)	5.1 (1.1 to 9.1)	5.9 (2.8 to 9.0)	7.4 (3.8 to 11.0)	2.4 (0.3 to 4.5)
Day 3 (n=114, 214, 203, 213)	7.9 (2.9 to 12.8)	8.4 (4.7 to 12.1)	14.8 (9.9 to 19.7)	3.3 (0.9 to 5.7)
Day 4 (n=116, 216, 199, 216)	6.0 (1.7 to 10.4)	11.6 (7.3 to 15.8)	18.6 (13.2 to 24.0)	5.6 (2.5 to 8.6)
Day 5 (n=119, 211, 196, 210)	7.6 (2.8 to 12.3)	14.2 (9.5 to 18.9)	26.5 (20.3 to 32.7)	9.5 (5.6 to 13.5)
Day 6 (n=119, 213, 207, 214)	10.9 (5.3 to 16.5)	15.0 (10.2 to 19.8)	25.1 (19.2 to 31.0)	14.0 (9.4 to 18.7)
Day 7 (n=108, 214, 208, 216)	11.1 (5.2 to 17.0)	20.1 (14.7 to 25.5)	28.8 (22.7 to 35.0)	13.4 (8.9 to 18.0)
Day 8 (n=118, 210, 207, 212)	14.4 (8.1 to 20.7)	21.4 (15.9 to 27.0)	33.3 (26.9 to 39.8)	16.5 (11.5 to 21.5)
Day 9 (n=115, 204, 208, 209)	13.0 (6.9 to 19.2)	24.0 (18.2 to 29.9)	34.1 (27.7 to 40.6)	14.8 (10.0 to 19.7)
Day 10 (n=114, 203, 207, 210)	13.2 (7.0 to 19.4)	25.6 (19.6 to 31.6)	34.3 (27.8 to 40.8)	17.1 (12.0 to 22.2)
Day 11 (n=118, 201, 210, 210)	12.7 (6.7 to 18.7)	25.4 (19.4 to 31.4)	39.5 (32.9 to 46.1)	20.5 (15.0 to 25.9)
Day 12 (n=117, 204, 202, 215)	12.0 (6.1 to 17.8)	25.5 (19.5 to 31.5)	44.1 (37.2 to 50.9)	21.9 (16.3 to 27.4)
Day 13 (n=114, 196, 203, 212)	13.2 (7.0 to 19.4)	30.6 (24.2 to 37.1)	43.8 (37.0 to 50.7)	23.6 (17.9 to 29.3)
Day 14 (n=121, 210, 199, 212)	15.7 (9.2 to 22.2)	31.4 (25.1 to 37.7)	45.7 (38.8 to 52.7)	24.5 (18.7 to 30.3)
Day 15 (n=117, 207, 208, 211)	11.1 (5.4 to 16.8)	30.4 (24.2 to 36.7)	49.0 (42.2 to 55.8)	26.5 (20.6 to 32.5)
Week 2 (n=130, 236, 226, 239)	13.8 (7.9 to 19.8)	31.8 (25.8 to 37.7)	49.1 (42.6 to 55.6)	26.4 (20.8 to 31.9)
Week 4 (n=124, 224, 214, 232)	20.2 (13.1 to 27.2)	44.6 (38.1 to 51.2)	59.3 (52.8 to 65.9)	45.3 (38.9 to 51.7)
Week 8 (n=122, 221, 214, 229)	27.0 (19.2 to 34.9)	47.5 (40.9 to 54.1)	64.0 (57.6 to 70.4)	50.7 (44.2 to 57.1)
Week 12 (n=121, 221, 217, 224)	28.9 (20.8 to 37.0)	47.5 (40.9 to 54.1)	63.1 (56.7 to 69.6)	54.5 (47.9 to 61.0)
Week 16 (n=94, 168, 172, 189)	28.7 (19.6 to 37.9)	47.0 (39.5 to 54.6)	62.8 (55.6 to 70.0)	57.1 (50.1 to 64.2)

PF-04965842 versus placebo

Statistical analysis description

Week 2: Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity.

Comparison groups

Placebo up to Week (Wk)16 v PF-04965842 100 mg + Placebo Injection up to Week 16

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0002

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

17.9

Confidence interval

level

95%

sides

2-sided

lower limit

9.5

upper limit

26.3

PF-04965842 versus placebo

Statistical analysis description

Comparison groups

Placebo up to Week (Wk)16 v PF-04965842 200 mg + Placebo Injection up to Week 16

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

34.9

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

43.7

PF-04965842 versus dupilumab

Statistical analysis description

Week 2: Difference in percentage (PF-04965842 versus dupilumab) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity.

Comparison groups

PF-04965842 100 mg + Placebo Injection up to Week 16 v Dupilumab 300 mg + Oral Placebo up to Week 16

Number of subjects included in analysis

480

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2084

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

13.4

PF-04965842 versus dupilumab

Statistical analysis description

Comparison groups

PF-04965842 200 mg + Placebo Injection up to Week 16 v Dupilumab 300 mg + Oral Placebo up to Week 16

Number of subjects included in analysis

468

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

22.1

Confidence interval

level

95%

sides

2-sided

lower limit

13.5

upper limit

30.7

Secondary: Percentage of Subjects Achieving IGA Response of Clear (0) or Almost Clear (1) and a Reduction of >=2 Points From Baseline at Week 2, 4, 8 and 16

Top of page

End point title

Percentage of Subjects Achieving IGA Response of Clear (0) or Almost Clear (1) and a Reduction of >=2 Points From Baseline at Week 2, 4, 8 and 16 ^[4]

End point description

IGA assessed severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded sole, palms and scalp. FAS analysed till Week 16. Here, “n” signifies the number of subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8 and 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: Percentage of subjects
number (confidence interval 95%)
Week 2 (n=128, 230, 223, 236)	6.3 (2.1 to 10.4)	15.2 (10.6 to 19.9)	18.4 (13.3 to 23.5)	4.7 (2.0 to 7.4)
Week 4 (n=129, 234, 223, 238)	6.2 (2.0 to 10.4)	25.2 (19.6 to 30.8)	31.4 (25.3 to 37.5)	18.9 (13.9 to 23.9)
Week 8 (n=129, 232, 225, 239)	10.1 (4.9 to 15.3)	35.8 (29.6 to 41.9)	50.7 (44.1 to 57.2)	28.5 (22.7 to 34.2)
Week 16 (n=124, 230, 221, 232)	12.9 (7.0 to 18.8)	34.8 (28.6 to 40.9)	47.5 (40.9 to 54.1)	38.8 (32.5 to 45.1)

PF-04965842 versus placebo

Statistical analysis description

Week 16: Difference in percentage (PF-04965842 versus placebo) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity.

Comparison groups

Placebo up to Week (Wk)16 v PF-04965842 100 mg + Placebo Injection up to Week 16

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

22.1

Confidence interval

level

95%

sides

2-sided

lower limit

13.7

upper limit

30.5

PF-04965842 versus placebo

Statistical analysis description

Comparison groups

Placebo up to Week (Wk)16 v PF-04965842 200 mg + Placebo Injection up to Week 16

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

26.3

upper limit

43.7

PF-04965842 versus dupilumab

Statistical analysis description

Week 16: Difference in percentage (PF-04965842 versus dupilumab) and CI for difference were calculated based on the weighted average of difference by disease severity group using the normal approximation of binomial proportions. P-value was adjusted by baseline disease severity.

Comparison groups

PF-04965842 100 mg + Placebo Injection up to Week 16 v Dupilumab 300 mg + Oral Placebo up to Week 16

Number of subjects included in analysis

480

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Percentage

Point estimate

-3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-12.2

upper limit

5.2

PF-04965842 versus dupilumab

Statistical analysis description

Comparison groups

PF-04965842 200 mg + Placebo Injection up to Week 16 v Dupilumab 300 mg + Oral Placebo up to Week 16

Number of subjects included in analysis

468

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Percentage

Point estimate

9.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

18.5

Secondary: Percentage of Subjects Achieving EASI Response >=75% Improvement From Baseline at Week 2, 4, 8 and 16

Top of page

End point title

Percentage of Subjects Achieving EASI Response >=75% Improvement From Baseline at Week 2, 4, 8 and 16 ^[5]

End point description

EASI evaluates severity of subjects' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); (A =EASI area score) ranged from 0.0 to 72.0, higher scores = greater severity of AD. FAS analysed till Week 16. Here, “n” signifies the number of subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8 and 16

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: Percentage of subjects
number (confidence interval 95%)
Week 2 (n= 128, 228, 223, 235)	10.9 (5.5 to 16.3)	25.4 (19.8 to 31.1)	30.0 (24.0 to 36.1)	14.0 (9.6 to 18.5)
Week 4 (n= 128, 233, 223, 238)	15.6 (9.3 to 21.9)	44.6 (38.3 to 51.0)	57.4 (50.9 to 63.9)	38.2 (32.1 to 44.4)
Week 8 (n= 129, 232, 224, 239)	18.6 (11.9 to 25.3)	55.6 (49.2 to 62.0)	67.9 (61.7 to 74.0)	52.7 (46.4 to 59.0)
Week 16 (n= 124, 229, 221, 232)	30.6 (22.5 to 38.8)	60.3 (53.9 to 66.6)	71.0 (65.1 to 77.0)	65.5 (59.4 to 71.6)

PF-04965842 versus placebo

Statistical analysis description

Comparison groups

Placebo up to Week (Wk)16 v PF-04965842 100 mg + Placebo Injection up to Week 16

Number of subjects included in analysis

369

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in percentage

Point estimate

24.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

34.1

PF-04965842 versus placebo

Statistical analysis description

Comparison groups

Placebo up to Week (Wk)16 v PF-04965842 200 mg + Placebo Injection up to Week 16

Number of subjects included in analysis

357

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Cochran-Mantel-Haenszel

Parameter type

Difference in Percentage

Point estimate

30.1

Confidence interval

level

95%

sides

2-sided

lower limit

20.3

upper limit

39.8

PF-04965842 versus dupilumab

Statistical analysis description

Comparison groups

Placebo up to Week (Wk)16 v Dupilumab 300 mg + Oral Placebo up to Week 16

Number of subjects included in analysis

373

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Percentage

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-9.6

upper limit

4.2

PF-04965842 versus dupilumab

Statistical analysis description

Comparison groups

PF-04965842 100 mg + Placebo Injection up to Week 16 v Dupilumab 300 mg + Oral Placebo up to Week 16

Number of subjects included in analysis

480

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Difference in Percentage

Point estimate

3.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

9.6

Secondary: Percentage of Subjects Achieving EASI Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16

Top of page

End point title

Percentage of Subjects Achieving EASI Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16 ^[6]

End point description

EASI evaluates severity of subjects' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin] and lower limbs [including buttocks]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (>0 to <10%), 2 (10 to <30%), 3 (30 to <50%), 4 (50 to <70%), 5 (70 to <90%) and 6 (90 to 100%). Total EASI score =0.1*Ah*(Eh+Ih+Exh+Lh) + 0.2*Au*(Eu+Iu+ExU+Lu) + 0.3*At*(Et+It+Ext+Lt) + 0.4*Al*(El+Il+Exl+Ll); (A =EASI area score) ranged from 0.0 to 72.0, higher scores = greater severity of AD. FAS analysed till Week 16. Here, “n” signifies the number of subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12 and 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: Percentage of subjects
number (confidence interval 95%)
Week 2 (n=128, 228, 223, 235)	21.9 (14.7 to 29.0)	53.1 (46.6 to 59.5)	60.5 (54.1 to 67.0)	35.7 (29.6 to 41.9)
Week 4 (n=128, 233, 223, 238)	39.8 (31.4 to 48.3)	73.4 (67.7 to 79.1)	78.5 (73.1 to 83.9)	66.8 (60.8 to 72.8)
Week 8 (n=129, 232, 224, 239)	48.8 (40.2 to 57.5)	78.9 (73.6 to 84.1)	88.4 (84.2 to 92.6)	77.4 (72.1 to 82.7)
Week 12 (n=129, 235, 219, 241)	52.7 (44.1 to 61.3)	75.3 (69.8 to 80.8)	86.3 (81.7 to 90.9)	80.9 (76.0 to 85.9)
Week 16 (n=124, 229, 221, 232)	57.3 (48.6 to 66.0)	81.2 (76.2 to 86.3)	87.3 (82.9 to 91.7)	84.1 (79.3 to 88.8)

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving EASI Response >=90% Improvement From Baseline at Week 2, 4, 8, 12 and 16

Top of page

End point title

Percentage of Subjects Achieving EASI Response >=90% Improvement From Baseline at Week 2, 4, 8, 12 and 16 ^[7]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12 and 16

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: Percentage of subjects
number (confidence interval 95%)
Week 2 (n=128, 228, 223, 235)	2.3 (0.0 to 5.0)	8.3 (4.7 to 11.9)	11.2 (7.1 to 15.4)	2.6 (0.5 to 4.6)
Week 4 (n=128, 233, 223, 238)	6.3 (2.1 to 10.4)	20.2 (15.0 to 25.3)	32.3 (26.2 to 38.4)	12.2 (8.0 to 16.3)
Week 8 (n=129, 232, 224, 239)	7.8 (3.1 to 12.4)	30.6 (24.7 to 36.5)	47.3 (40.8 to 53.9)	24.3 (18.8 to 29.7)
Week 12 (n=129, 235, 219, 241)	10.1 (4.9 to 15.3)	36.6 (30.4 to 42.8)	46.1 (39.5 to 52.7)	34.9 (28.8 to 40.9)
Week 16 (n=124, 229, 221, 232)	11.3 (5.7 to 16.9)	38.0 (31.7 to 44.3)	48.9 (42.3 to 55.5)	38.8 (32.5 to 45.1)

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving EASI Response =100% Improvement From Baseline at Week 2, 4, 8, 12 and 16

Top of page

End point title

Percentage of Subjects Achieving EASI Response =100% Improvement From Baseline at Week 2, 4, 8, 12 and 16 ^[8]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12 and 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: Percentage of subjects
number (confidence interval 95%)
Week 2 (n=128, 228, 223, 235)	0 (0.0 to 2.8)	1.3 (0.0 to 2.8)	4.5 (1.8 to 7.2)	0.4 (0.0 to 1.3)
Week 4 (n=128, 233, 223, 238)	0 (0.0 to 2.8)	2.6 (0.5 to 4.6)	7.2 (3.8 to 10.6)	2.5 (0.5 to 4.5)
Week 8 (n=129, 232, 224, 239)	0 (0.0 to 2.8)	6.0 (3.0 to 9.1)	11.6 (7.4 to 15.8)	2.1 (0.3 to 3.9)
Week 12 (n=129, 235, 219, 241)	1.6 (0.0 to 3.7)	8.1 (4.6 to 11.6)	12.3 (8.0 to 16.7)	6.6 (3.5 to 9.8)
Week 16 (n=124, 229, 221, 232)	4.0 (0.6 to 7.5)	12.7 (8.4 to 17.0)	13.6 (9.1 to 18.1)	5.2 (2.3 to 8.0)

No statistical analyses for this end point

Secondary: Time From Baseline to First Achieve at Least 4 Points Improvement in the Severity of Pruritus NRS

Top of page

End point title

Time From Baseline to First Achieve at Least 4 Points Improvement in the Severity of Pruritus NRS ^[9]

End point description

Subjects were asked to assess their worst pruritus/itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst possible itching), where higher scores indicated greater severity. FAS analysed till Week 16. Subjects with a baseline numeric rating scale score for severity of pruritus >=4 were included in the analysis. Here, “99999” signifies median and upper limit for 95% CI could not be estimated because there were insufficient number of subjects with event.

End point type

Secondary

End point timeframe

Baseline up to Week 16

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	130	236	226	240
Units: Days
median (confidence interval 95%)	99999 (84.0 to 99999)	29.0 (16.0 to 56.0)	13.0 (10.0 to 16.0)	31.0 (29.0 to 57.0)

No statistical analyses for this end point

Secondary: Change From Baseline in Percentage Body Surface Area (BSA) at Week 2, 4, 8, 12 and 16

Top of page

End point title

Change From Baseline in Percentage Body Surface Area (BSA) at Week 2, 4, 8, 12 and 16 ^[10]

End point description

4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of subject's hand with fingers in a closed position) fitting in the affected area of a body region was estimated. Maximum number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area of body region equivalent to 1 handprint: 1 handprint was equal to 10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. Percent BSA for a body region was calculated as = total number of handprints in a body region * % surface area equivalent to 1 handprint. Overall % BSA for an individual: arithmetic mean of % BSA of all 4 body regions, ranges from 0 to 100%, with higher values representing greater severity of AD. FAS analysed till Week 16.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12 and 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: Percentage BSA
least squares mean (confidence interval 95%)
Change at Week 2	-7.6 (-10.4 to -4.8)	-19.5 (-21.6 to -17.4)	-21.4 (-23.5 to -19.3)	-14.0 (-16.1 to -11.9)
Change at Week 4	-14.3 (-17.2 to -11.4)	-26.8 (-29.0 to -24.7)	-30.7 (-32.9 to -28.4)	-24.0 (-26.2 to -21.9)
Change at Week 8	-16.2 (-19.0 to -13.4)	-30.3 (-32.4 to -28.2)	-36.4 (-38.6 to -34.3)	-29.8 (-31.8 to -27.7)
Change at Week 12	-17.1 (-20.1 to -14.1)	-31.6 (-33.8 to -29.4)	-37.4 (-39.6 to -35.1)	-32.5 (-34.7 to -30.3)
Change at Week 16	-19.6 (-22.6 to -16.6)	-32.9 (-35.1 to -30.7)	-39.0 (-41.3 to -36.8)	-34.4 (-36.6 to -32.2)

No statistical analyses for this end point

Secondary: Percentage BSA at Week 18 and 20

Top of page

End point title

Percentage BSA at Week 18 and 20

End point description

4 body regions were evaluated: head and neck, upper limbs, trunk (including axillae and groin) and lower limbs (including buttocks). Scalp, palms and soles were excluded. BSA was calculated using handprint method. Number of handprints (size of subject’s hand with fingers in closed position) fitting in the affected area of body region was estimated. Maximum number of handprints were 10 for head and neck, 20 for upper limbs, 30 for trunk and 40 for lower limbs. Surface area (SA) of body region equivalent to 1 handprint: 1 handprint=10% for head and neck, 5% for upper limbs, 3.33% for trunk and 2.5% for lower limbs. %BSA for body region was calculated as=total number of handprints in body region*% SA equivalent to 1 handprint. Overall %BSA for individual: arithmetic mean of %BSA of all 4 body regions, ranges from 0-100%, with higher values representing greater severity of AD. FAS analysed post Week 16. Here, “n” signifies the number of subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Week 18 and 20

End point values	Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20	Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20
Number of subjects analysed	60	57	217	208	223
Units: Percentage BSA
arithmetic mean (standard deviation)
Week 18 (n=55, 51, 200, 198, 204)	22.0 ± 23.67	20.8 ± 22.7	14.8 ± 19.3	9.8 ± 13.6	13.2 ± 16.4
Week 20 (n=57, 56, 212, 197, 214)	18.0 ± 21.2	16.0 ± 19.7	14.2 ± 19.0	10.3 ± 14.2	13.2 ± 16.3

No statistical analyses for this end point

Secondary: Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8, 12 and 16

Top of page

End point title

Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8, 12 and 16 ^[11]

End point description

Subject responded to the following question: "Overall, how would you describe your Atopic Dermatitis right now?" on a scale: 0= clear; 1= almost clear; 2= mild; 3= moderate; and 4= severe. Higher scores indicated more severity. FAS analysed till Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12 and 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	241
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-0.5 (-0.6 to -0.3)	-0.8 (-0.9 to -0.7)	-1.0 (-1.1 to -0.9)	-0.7 (-0.8 to -0.6)
Change at Week 4	-0.5 (-0.7 to -0.4)	-1.0 (-1.1 to -0.9)	-1.4 (-1.5 to -1.3)	-1.1 (-1.2 to -0.9)
Change at Week 8	-0.6 (-0.7 to -0.4)	-1.1 (-1.3 to -1.0)	-1.5 (-1.6 to -1.4)	-1.3 (-1.4 to -1.1)
Change at Week 12	-0.7 (-0.8 to -0.5)	-1.2 (-1.3 to -1.1)	-1.6 (-1.7 to -1.5)	-1.3 (-1.4 to -1.2)
Change at Week 16	-0.7 (-0.9 to -0.6)	-1.2 (-1.3 to -1.0)	-1.6 (-1.7 to -1.5)	-1.4 (-1.5 to -1.2)

No statistical analyses for this end point

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 12 and 16

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End point title

Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 12 and 16 ^[12]

End point description

DLQI is a 10-item questionnaire that measures the impact of skin disease. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of subjects. FAS analysed till Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 2, 12 and 16

Notes
[12] - 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	241
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 2	-4.5 (-5.5 to -3.5)	-6.7 (-7.5 to -6.0)	-8.5 (-9.2 to -7.8)	-6.7 (-7.4 to -5.9)
Change at Week 12	-6.2 (-7.1 to -5.3)	-8.7 (-9.4 to -8.0)	-11.0 (-11.7 to -10.3)	-9.9 (-10.6 to -9.2)
Change at Week 16	-6.2 (-7.1 to -5.3)	-9.0 (-9.7 to -8.4)	-11.7 (-12.4 to -11.1)	-10.8 (-11.4 to -10.1)

No statistical analyses for this end point

Secondary: DLQI at Week 20

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End point title

DLQI at Week 20

End point description

DLQI is a 10-item questionnaire that measures the impact of skin disease. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of subjects. FAS analysed post Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 20

End point values	Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20	Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20
Number of subjects analysed	55	55	210	198	216
Units: units on a scale
arithmetic mean (standard deviation)	5.3 ± 5.3	5.8 ± 5.7	6.3 ± 5.8	4.3 ± 4.7	5.6 ± 4.8

No statistical analyses for this end point

Secondary: Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Index Value at Week 12 and 16

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End point title

Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Index Value at Week 12 and 16 ^[13]

End point description

EQ-5D-5L: standardised subject completed questionnaire consisted of 2 components: a health state profile and optional VAS. EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a subject responded "no problems" for each 5 dimensions, then health state was coded as "11111" with predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. US value sets (with all possible health states) was used for adults in study, range from 1 to -0.109. Higher (positive) scores = better health state. . FAS analysed till Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 12 and 16

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	241
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 12	0.051 (0.032 to 0.070)	0.101 (0.087 to 0.115)	0.127 (0.113 to 0.141)	0.104 (0.091 to 0.118)
Change at Week 16	0.067 (0.047 to 0.087)	0.093 (0.079 to 0.107)	0.133 (0.119 to 0.148)	0.113 (0.099 to 0.127)

No statistical analyses for this end point

Secondary: Change From Baseline in EQ-5D-5L Visual Analogue Scale (VAS) Score at Week 12 and 16

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End point title

Change From Baseline in EQ-5D-5L Visual Analogue Scale (VAS) Score at Week 12 and 16 ^[14]

End point description

EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D VAS was used to record a subject's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. FAS analysed till Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 12 and 16

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	241
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 12	7.975 (5.161 to 10.789)	11.337 (9.272 to 13.401)	17.373 (15.270 to 19.476)	14.939 (12.900 to 16.978)
Change at Week 16	7.840 (4.952 to 10.727)	11.223 (9.129 to 13.318)	16.711 (14.581 to 18.841)	14.405 (12.315 to 16.496)

No statistical analyses for this end point

Secondary: EQ-5D-5L- Index Value at Week 20

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End point title

EQ-5D-5L- Index Value at Week 20

End point description

EQ-5D-5L: standardised subject completed questionnaire consisted of 2 components: a health state profile and optional VAS. EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Responses to 5 dimensions comprised a health state/a single utility index value. E.g. if a subject responded "no problems" for each 5 dimensions, then health state was coded as "11111" with predefined index value to it. Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol. US value sets (with all possible health states) was used for adults in study, range from 1 to -0.109. Higher (positive) scores = better health state. FAS analysed post Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 20

End point values	Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20	Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20
Number of subjects analysed	55	55	210	197	216
Units: units on a scale
arithmetic mean (standard deviation)	0.905 ± 0.097	0.894 ± 0.122	0.883 ± 0.124	0.917 ± 0.109	0.890 ± 0.109

No statistical analyses for this end point

Secondary: EQ-5D-5L- VAS Score at Week 20

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End point title

EQ-5D-5L- VAS Score at Week 20

End point description

EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D VAS was used to record a subject's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state. FAS analysed post Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 20

End point values	Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20	Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20
Number of subjects analysed	55	55	210	197	216
Units: units on a scale
arithmetic mean (standard deviation)	78.2 ± 16.3	78.5 ± 20.2	76.7 ± 19.5	82.1 ± 17.1	79.6 ± 18.0

No statistical analyses for this end point

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) – Anxiety Scale at Week 12 and 16

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End point title

Change From Baseline in Hospital Anxiety and Depression Scale (HADS) – Anxiety Scale at Week 12 and 16 ^[15]

End point description

HADS: subject rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-Anxiety (HADS-A) scale and HADS-Depression (HADS-D) scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalised anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-A: sum of all 7 items resulted in score range of 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicating greater severity of anxiety. FAS analysed till Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Weeks 12 and 16

Notes
[15] - 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 12	-0.4 (-0.9 to 0.1)	-1.2 (-1.5 to -0.8)	-1.6 (-2.0 to -1.2)	-1.4 (-1.7 to -1.0)
Change at Week 16	-0.4 (-0.9 to 0.1)	-1.2 (-1.6 to -0.8)	-2.0 (-2.4 to -1.6)	-1.5 (-1.9 to -1.1)

No statistical analyses for this end point

Secondary: Change From Baseline in HADS – Depression Scale at Week 12 and 16

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End point title

Change From Baseline in HADS – Depression Scale at Week 12 and 16 ^[16]

End point description

HADS: subject rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalised anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-D: sum of all 7 items resulted in score range of 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicating greater severity of depression symptoms. FAS analysed till Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 12 and 16

Notes
[16] - 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 12	-0.3 (-0.7 to 0.2)	-1.3 (-1.6 to -0.9)	-1.6 (-1.9 to -1.2)	-1.3 (-1.6 to -0.9)
Change at Week 16	-0.3 (-0.8 to 0.2)	-1.0 (-1.4 to -0.7)	-1.6 (-1.9 to -1.2)	-1.2 (-1.5 to -0.8)

No statistical analyses for this end point

Secondary: HADS – Anxiety Scale at Week 20

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End point title

HADS – Anxiety Scale at Week 20

End point description

HADS: subject rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalised anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-A: sum of all 7 items resulted in score range of 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicating greater severity of anxiety. FAS analysed post Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 20

End point values	Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20	Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20
Number of subjects analysed	55	55	209	197	215
Units: units on a scale
arithmetic mean (standard deviation)	3.4 ± 3.2	4.5 ± 4.5	4.0 ± 3.8	3.1 ± 3.1	3.7 ± 3.4

No statistical analyses for this end point

Secondary: HADS – Depression Scale at Week 20

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End point title

HADS – Depression Scale at Week 20

End point description

HADS: subject rated 14-item questionnaire. HADS consisted of 2 subscales: HADS-A scale and HADS-D scale, both of these subscales comprised of 7 items each. Each item was rated on a 4-point scale, score range from 0 to 3, where higher scores indicates more anxiety/depression symptoms. HADS-A assesses state of generalised anxiety (anxious mood, restlessness, anxious thoughts, panic attacks). HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). HADS-D: sum of all 7 items resulted in score range of 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicating greater severity of depression symptoms. FAS analysed post Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 20

End point values	Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20	Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20
Number of subjects analysed	55	55	209	197	215
Units: units on a scale
arithmetic mean (standard deviation)	2.6 ± 3.4	3.6 ± 3.7	2.8 ± 3.2	2.2 ± 3.1	2.7 ± 3.3

No statistical analyses for this end point

Secondary: Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 12 and 16

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End point title

Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 12 and 16 ^[17]

End point description

POEM is a 7-item subject reported outcome (PRO) measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item is scored as following: "no days (0)", "1-2 days (1)", "3-4 days (2)", "5-6 days (3)" and "every day (4)". The score ranges from 0 to 28, where higher score indicated greater severity. FAS analysed till Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 12 and 16

Notes
[17] - 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	241
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 12	-5.1 (-6.3 to -3.9)	-9.6 (-10.5 to -8.6)	-12.6 (-13.6 to -11.7)	-10.8 (-11.7 to -9.9)
Change at Week 16	-5.0 (-6.3 to -3.8)	-9.2 (-10.1 to -8.2)	-12.5 (-13.4 to -11.6)	-10.8 (-11.8 to -9.9)

No statistical analyses for this end point

Secondary: POEM at Week 20

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End point title

POEM at Week 20

End point description

POEM is a 7-item subject reported outcome (PRO) measure used to assess the impact of AD (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) over the past week. Each item is scored as following: "no days (0)", "1-2 days (1)", "3-4 days (2)", "5-6 days (3)" and "every day (4)". The score ranges from 0 to 28, where higher score indicated greater severity. FAS analysed post Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 20

End point values	Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20	Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20
Number of subjects analysed	55	55	209	196	215
Units: units on a scale
arithmetic mean (standard deviation)	10.7 ± 6.8	9.6 ± 7.8	11.6 ± 7.7	8.6 ± 7.0	11.0 ± 6.9

No statistical analyses for this end point

Secondary: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score Week 1 to Week 16

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End point title

Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score Week 1 to Week 16 ^[18]

End point description

PSAAD is a daily subject reported symptom electronic diary. Subjects rated their symptoms of AD over the past 24 hours, using 11 items (itchy skin, painful skin, dry skin, flaky skin, cracked skin, bumpy skin, red skin, discolored skin [lighter or darker], bleeding from skin, seeping or oozing fluid from skin [other than blood], and skin swelling). Subject had to think about all the areas of their body affected by their skin condition and chose the number that best described their experience for each of the 11 items, from 0 (no symptoms) to 10 (extreme symptoms), higher scores signified worse skin condition. Total PSAAD score = arithmetic mean of 11 items, 0 (no symptoms) to 10 (extreme symptoms), where higher score = worse skin condition. FAS analysed till Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 1 to Week 16

Notes
[18] - 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	130	237	225	241
Units: units on a scale
least squares mean (confidence interval 95%)
Change at Week 1	-0.5 (-0.8 to -0.3)	-1.1 (-1.3 to -0.9)	-1.3 (-1.5 to -1.2)	-0.9 (-1.1 to -0.8)
Change at Week 2	-0.9 (-1.2 to -0.7)	-1.8 (-2.0 to -1.6)	-2.3 (-2.5 to -2.1)	-1.6 (-1.8 to -1.4)
Change at Week 3	-1.1 (-1.4 to -0.8)	-2.2 (-2.4 to -2.0)	-2.8 (-3.0 to -2.6)	-2.1 (-2.3 to -1.9)
Change at Week 4	-1.4 (-1.7 to -1.1)	-2.4 (-2.6 to -2.2)	-3.0 (-3.3 to -2.8)	-2.4 (-2.7 to -2.2)
Change at Week 5	-1.5 (-1.8 to -1.2)	-2.6 (-2.8 to -2.4)	-3.2 (-3.5 to -3.0)	-2.7 (-2.9 to -2.5)
Change at Week 6	-1.5 (-1.8 to -1.2)	-2.6 (-2.8 to -2.4)	-3.3 (-3.6 to -3.1)	-2.8 (-3.1 to -2.6)
Change at Week 7	-1.6 (-1.9 to -1.2)	-2.7 (-2.9 to -2.4)	-3.4 (-3.6 to -3.1)	-2.9 (-3.2 to -2.7)
Change at Week 8	-1.5 (-1.9 to -1.2)	-2.7 (-2.9 to -2.4)	-3.4 (-3.7 to -3.2)	-3.0 (-3.2 to -2.7)
Change at Week 9	-1.7 (-2.0 to -1.4)	-2.7 (-2.9 to -2.4)	-3.5 (-3.8 to -3.3)	-3.1 (-3.3 to -2.8)
Change at Week 10	-1.7 (-2.0 to -1.4)	-2.7 (-2.9 to -2.4)	-3.5 (-3.8 to -3.3)	-3.1 (-3.4 to -2.9)
Change at Week 11	-1.6 (-1.9 to -1.3)	-2.7 (-2.9 to -2.4)	-3.5 (-3.8 to -3.3)	-3.2 (-3.4 to -2.9)
Change at Week 12	-1.6 (-2.0 to -1.3)	-2.7 (-3.0 to -2.5)	-3.6 (-3.8 to -3.3)	-3.2 (-3.5 to -3.0)
Change at Week 13	-1.7 (-2.0 to -1.4)	-2.8 (-3.1 to -2.6)	-3.7 (-3.9 to -3.4)	-3.3 (-3.6 to -3.1)
Change at Week 14	-1.6 (-1.9 to -1.3)	-2.8 (-3.1 to -2.6)	-3.6 (-3.9 to -3.4)	-3.4 (-3.6 to -3.2)
Change at Week 15	-1.7 (-2.0 to -1.4)	-2.9 (-3.1 to -2.6)	-3.6 (-3.8 to -3.4)	-3.4 (-3.6 to -3.1)
Change at Week 16	-1.7 (-2.0 to -1.3)	-2.8 (-3.1 to -2.6)	-3.6 (-3.8 to -3.4)	-3.4 (-3.6 to -3.2)

No statistical analyses for this end point

Secondary: PSAAD Total Score at Week 18 and 20

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End point title

PSAAD Total Score at Week 18 and 20

End point description

PSAAD is a daily subject reported symptom electronic diary. Subjects rated their symptoms of AD over the past 24 hours, using 11 items (itchy skin, painful skin, dry skin, flaky skin, cracked skin, bumpy skin, red skin, discolored skin [lighter or darker], bleeding from skin, seeping or oozing fluid from skin [other than blood], and skin swelling). Subject had to think about all the areas of their body affected by their skin condition and chose the number that best described their experience for each of the 11 items, from 0 (no symptoms) to 10 (extreme symptoms), higher scores signified worse skin condition. Total PSAAD score = arithmetic mean of 11 items, 0 (no symptoms) to 10 (extreme symptoms), where higher score = worse skin condition. FAS analysed post Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint and “n” signifies the number of subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Week 18 and 20

End point values	Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20	Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20
Number of subjects analysed	54	54	202	202	218
Units: units on a scale
arithmetic mean (standard deviation)
Week 18 (n=54, 54, 202, 202,218)	2.6 ± 1.9	3.0 ± 2.4	2.2 ± 1.9	1.7 ± 1.7	1.8 ± 1.5
Week 20 (n=54, 53, 201, 199,213)	2.5 ± 2.0	2.6 ± 2.3	2.2 ± 1.9	1.8 ± 1.8	2.0 ± 1.6

No statistical analyses for this end point

Secondary: Percentage of Subjects With Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16

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End point title

Percentage of Subjects With Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16 ^[19]

End point description

SCORAD:scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region-head and neck 9%, upper limbs 9% each, lower limbs 18% each, anterior trunk 18%, back 18%, 1% for genitals; score for each region was added to give A(0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2, severe=3; scores were summed to give B(0-18). C: pruritus and sleep, each of these 2 were scored by subject/caregiver using VAS where “0”=no itch/no sleeplessness; “10”=the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give C (0-20). The SCORAD was calculated: A/5 + 7*B/2 + C;range=0-103;higher values=worse outcome. FAS analysed till Week 16. Here, “n” signifies the number of subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8, 12 and 16

Notes
[19] - 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: Percentage of subjects
number (confidence interval 95%)
Week 2 (n=128, 233, 224, 237)	10.2 (4.9 to 15.4)	23.6 (18.2 to 29.1)	38.4 (32.0 to 44.8)	15.6 (11.0 to 20.2)
Week 4 (n=129, 234, 224, 238)	18.6 (11.9 to 25.3)	45.7 (39.3 to 52.1)	61.6 (55.2 to 68.0)	45.8 (39.5 to 52.1)
Week 8 (n=129, 234, 225, 239)	20.2 (13.2 to 27.1)	53.4 (47.0 to 59.8)	71.6 (65.7 to 77.5)	56.9 (50.6 to 63.2)
Week 12 (n=128, 234, 224, 238)	27.3 (19.6 to 35.1)	56.8 (50.5 to 63.2)	72.3 (66.5 to 78.2)	64.3 (58.2 to 70.4)
Week 16 (n=123, 228, 221, 231)	33.3 (25.0 to 41.7)	56.1 (49.7 to 62.6)	68.8 (62.7 to 74.9)	67.5 (61.5 to 73.6)

No statistical analyses for this end point

Secondary: Percentage of Subjects With SCORAD Response >=75% Improvement From Baseline at Week 2, 4, 8 12 and 16

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End point title

Percentage of Subjects With SCORAD Response >=75% Improvement From Baseline at Week 2, 4, 8 12 and 16 ^[20]

End point description

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8 12 and 16

Notes
[20] - 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: Percentage of subjects
number (confidence interval 95%)
Week 2 (n=128, 233, 224, 237)	1.6 (0.0 to 3.7)	6.4 (3.3 to 9.6)	8.5 (4.8 to 12.1)	0.8 (0.0 to 2.0)
Week 4 (n=129, 234, 224, 238)	3.1 (0.1 to 6.1)	12.4 (8.2 to 16.6)	25.4 (19.7 to 31.2)	7.1 (3.9 to 10.4)
Week 8 (n=129, 234, 225, 239)	3.1 (0.1 to 6.1)	19.2 (14.2 to 24.3)	41.3 (34.9 to 47.8)	16.3 (11.6 to 21.0)
Week 12 (n=128, 234, 224, 238)	6.3 (2.1 to 10.4)	25.6 (20.0 to 31.2)	39.3 (32.9 to 45.7)	26.1 (20.5 to 31.6)
Week 16 (n=123, 228, 221, 231)	10.6 (5.1 to 16.0)	26.8 (21.0 to 32.5)	40.3 (33.8 to 46.7)	29.4 (23.6 to 35.3)

No statistical analyses for this end point

Secondary: Change From Baseline in SCORAD Visual Analogue Scale (VAS) of Itch and Sleep Loss at Week 2, 4, 8 12 and 16

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End point title

Change From Baseline in SCORAD Visual Analogue Scale (VAS) of Itch and Sleep Loss at Week 2, 4, 8 12 and 16 ^[21]

End point description

SCORAD:scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region-head and neck 9%, upper limbs 9% each, lower limbs 18% each, anterior trunk 18%, back 18%, 1% for genitals; score for each region was added to give A(0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2, severe=3; scores were summed to give B(0-18). C: pruritus and sleep, each of these 2 were scored by subject/caregiver using VAS where “0”=no itch/no sleeplessness; “10”=the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give C (0-20). The SCORAD was calculated: A/5 + 7*B/2 + C;range=0-103;higher values=worse outcome. FAS analysed till Week 16. Here, ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 2, 4, 8 12 and 16

Notes
[21] - 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	129	237	225	241
Units: units on a scale
least squares mean (confidence interval 95%)
Itch: Change at Week 2	-1.5 (-1.9 to -1.2)	-2.9 (-3.2 to -2.7)	-3.7 (-4.0 to -3.4)	-2.4 (-2.7 to -2.1)
Itch: Change at Week 4	-2.2 (-2.6 to -1.8)	-3.7 (-4.0 to -3.4)	-4.6 (-4.9 to -4.3)	-3.7 (-4.0 to -3.4)
Itch: Change at Week 8	-2.3 (-2.7 to -1.9)	-3.9 (-4.2 to -3.6)	-4.9 (-5.2 to -4.6)	-4.2 (-4.5 to -3.9)
Itch: Change at Week 12	-2.4 (-2.9 to -2.0)	-3.9 (-4.3 to -3.6)	-5.0 (-5.3 to -4.7)	-4.4 (-4.7 to -4.1)
Itch: Change at Week 16	-2.7 (-3.1 to -2.3)	-3.8 (-4.1 to -3.5)	-4.8 (-5.1 to -4.5)	-4.5 (-4.8 to -4.2)
Sleep loss: Change at Week 2	-1.6 (-2.0 to -1.2)	-2.6 (-2.9 to -2.3)	-3.3 (-3.6 to -3.0)	-2.3 (-2.6 to -1.9)
Sleep loss: Change at Week 4	-2.3 (-2.7 to -1.9)	-3.4 (-3.7 to -3.1)	-4.2 (-4.5 to -3.9)	-3.4 (-3.7 to -3.1)
Sleep loss: Change at Week 8	-2.3 (-2.7 to -1.9)	-3.6 (-3.9 to -3.3)	-4.4 (-4.7 to -4.1)	-3.9 (-4.2 to -3.6)
Sleep loss: Change at Week 12	-2.4 (-2.8 to -2.0)	-3.7 (-4.0 to -3.4)	-4.6 (-4.9 to -4.3)	-4.2 (-4.5 to -3.9)
Sleep loss: Change at Week 16	-2.6 (-3.0 to -2.2)	-3.7 (-4.0 to -3.4)	-4.8 (-5.1 to -4.5)	-4.3 (-4.6 to -4.0)

No statistical analyses for this end point

Secondary: SCORAD VAS of Itch and Sleep Loss at Week 18 and 20

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End point title

SCORAD VAS of Itch and Sleep Loss at Week 18 and 20

End point description

SCORAD:scoring index for AD combining extent (A), severity (B), subjective symptoms (C). A: rule of 9 was used to calculate BSA affected by AD as a % of whole BSA for each body region-head and neck 9%, upper limbs 9% each, lower limbs 18% each, anterior trunk 18%, back 18%, 1% for genitals; score for each region was added to give A(0-100). B: severity of each sign (erythema; edema; oozing; excoriation; skin thickening; dryness) was assessed as none=0, mild=1, moderate=2, severe=3; scores were summed to give B(0-18). C: pruritus and sleep, each of these 2 were scored by subject/caregiver using VAS where “0”=no itch/no sleeplessness; “10”=the worst imaginable itch/sleeplessness, higher scores=worse symptoms. Scores for itch and sleeplessness were added to give C (0-20). The SCORAD was calculated: A/5 + 7*B/2 + C;range=0-103;higher values=worse outcome. FAS analysed post Week 16. Here, “n” signifies the number of subjects evaluable for the specified time points.

End point type

Secondary

End point timeframe

Week 18 and 20

End point values	Placebo up to Wk 16 then PF-04965842 100 mg Wk 16 to 20	Placebo up to Wk 16 then PF-04965842 200 mg Wk 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk>Oral Placebo Wk 16-20
Number of subjects analysed	60	57	217	208	223
Units: units on a scale
arithmetic mean (standard deviation)
Itch: Week 18 (n=56, 52, 204, 201, 206)	3.2 ± 2.6	2.7 ± 2.2	3.0 ± 2.5	2.3 ± 2.2	2.7 ± 2.2
Itch: Week 20 (n=58, 57, 212, 199, 218)	2.9 ± 2.4	2.6 ± 2.4	3.2 ± 2.6	2.3 ± 2.3	2.8 ± 2.2
Sleep loss: Week 18 (n=56, 52, 204, 201, 206)	2.2 ± 2.3	2.3 ± 2.3	2.1 ± 2.3	1.6 ± 2.1	1.8 ± 2.0
Sleep loss: Week 20 (n=58, 57, 212, 199, 218)	2.1 ± 2.2	2.0 ± 2.3	2.4 ± 2.6	1.5 ± 2.1	1.7 ± 2.1

No statistical analyses for this end point

Secondary: Least Square Mean of Number of Steroid-free Days From Baseline up to Week 16

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End point title

Least Square Mean of Number of Steroid-free Days From Baseline up to Week 16 ^[22]

End point description

Number of days when a corticosteroid as a concomitant medication was not used up to Week 16 is reported as Least square mean in this outcome measure. FAS analysed till Week 16.

End point type

Secondary

End point timeframe

Baseline up to Week 16

Notes
[22] - 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: Data have been for reported for those arms which were applicable till Week 16.

End point values	Placebo up to Week (Wk)16	PF-04965842 100 mg + Placebo Injection up to Week 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16
Number of subjects analysed	131	238	226	242
Units: Days
least squares mean (confidence interval 95%)	21.8 (14.9 to 28.8)	30.2 (25.1 to 35.4)	33.6 (28.3 to 38.9)	28.1 (23.0 to 33.2)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

For reporting arms till Week 16 analysis: Baseline up to Week 16; For reporting arms post Week 16 analysis: Week 16 to Week 24 (28 days after last dose of study drug)

Adverse event reporting additional description

Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 subject and as non-serious in another subject or 1 subject may have experienced both serious and non-serious event during study. Safety analysis set analysed.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

22.1, 23.0

Reporting group title

Placebo up to Wk 16

Reporting group description

Subjects were randomised to receive oral placebo matched to PF-04965842 once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 till Week 16.

Reporting group title

PF-04965842 100 mg + Placebo Injection up to Wk 16

Reporting group description

Subjects were randomised to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16.

Reporting group title

PF-04965842 200 mg + Placebo Injection up to Week 16

Reporting group description

Subjects were randomised to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16.

Reporting group title

Dupilumab 300 mg + Oral Placebo up to Week 16

Reporting group description

Subjects were randomised to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Wk 16.

Reporting group title

Placebo up to Week 16 then PF-04965842 100 mg Week 16 to 20

Reporting group description

Reporting group title

Placebo up to Week 16 then PF-04965842 200 mg Week 16 to 20

Reporting group description

Reporting group title

PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20

Reporting group description

Subjects who were randomised to receive PF-04965842 100 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 100 mg tablet orally once daily post Week 16 up to Week 20.

Reporting group title

PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20

Reporting group description

Subjects who were randomised to receive PF-04965842 200 mg tablet orally once daily with subcutaneous injectable placebo matched to dupilumab every other week from Day 1 to Week 16, received PF-04965842 200 mg tablet orally once daily post Week 16 up to Week 20.

Reporting group title

Dupilumab 300mg+Oral Placebo up to Wk16>Oral Placebo Wk 16-20

Reporting group description

Subjects who were randomised to receive dupilumab 300 mg subcutaneous injection every other week with oral placebo matched to PF-04965842 once daily from Day 1 to Week 16, received oral placebo matched to PF-04965842 once daily post Week 16 up to Week 20.

Serious adverse events	Placebo up to Wk 16	PF-04965842 100 mg + Placebo Injection up to Wk 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16	Placebo up to Week 16 then PF-04965842 100 mg Week 16 to 20	Placebo up to Week 16 then PF-04965842 200 mg Week 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk16>Oral Placebo Wk 16-20
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 131 (3.82%)	6 / 238 (2.52%)	2 / 226 (0.88%)	2 / 242 (0.83%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	1 / 223 (0.45%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chills
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactic reaction
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Breast mass
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine haemorrhage
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Interstitial lung disease
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 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
Investigations
Aspartate aminotransferase increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences causally related to treatment / all	1 / 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
Injury, poisoning and procedural complications
Ankle fracture
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus injury
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscle injury
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tendon injury
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Pancytopenia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 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
Gastrointestinal disorders
Abdominal pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Drug-induced liver injury
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 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
Skin and subcutaneous tissue disorders
Dermatitis atopic
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences causally related to treatment / all	1 / 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
Night sweats
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Hydronephrosis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nephrolithiasis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ureterolithiasis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract obstruction
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Diarrhoea infectious
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oral herpes
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 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
Pneumonia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 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
Enteritis infectious
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (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
deaths causally related to treatment / all	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: 0%

Non-serious adverse events	Placebo up to Wk 16	PF-04965842 100 mg + Placebo Injection up to Wk 16	PF-04965842 200 mg + Placebo Injection up to Week 16	Dupilumab 300 mg + Oral Placebo up to Week 16	Placebo up to Week 16 then PF-04965842 100 mg Week 16 to 20	Placebo up to Week 16 then PF-04965842 200 mg Week 16 to 20	PF-04965842 100mg+Placebo Inj. Wk 16>PF-04965842 100mg Wk16-20	PF-04965842 200mg+Placebo Inj. Wk 16>PF-04965842 200mg Wk16-20	Dupilumab 300mg+Oral Placebo up to Wk16>Oral Placebo Wk 16-20
Total subjects affected by non serious adverse events
subjects affected / exposed	68 / 131 (51.91%)	121 / 238 (50.84%)	140 / 226 (61.95%)	120 / 242 (49.59%)	13 / 60 (21.67%)	16 / 57 (28.07%)	50 / 217 (23.04%)	45 / 208 (21.63%)	31 / 223 (13.90%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Skin papilloma
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	1	0	1	0	0	0	0	0
Vascular disorders
Aortic stenosis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Essential hypertension
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Hot flush
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Hypertension
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	2 / 238 (0.84%)	3 / 226 (1.33%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	2 / 208 (0.96%)	1 / 223 (0.45%)
occurrences all number	0	2	3	0	0	0	0	2	1
Surgical and medical procedures
Rotator cuff repair
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Tooth extraction
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Pregnancy, puerperium and perinatal conditions
Pregnancy
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	0	1	1	0	0	0	0	1
General disorders and administration site conditions
Asthenia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	2 / 238 (0.84%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	2	2	0	0	0	0	0	0
Chest pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	2 / 238 (0.84%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0
Chills
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Cyst
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Fatigue
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	2 / 238 (0.84%)	3 / 226 (1.33%)	2 / 242 (0.83%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	3	4	2	0	0	0	0	0
Feeling abnormal
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Feeling cold
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Feeling hot
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Inflammation
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Influenza like illness
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Injection site erythema
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Injection site oedema
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Injection site pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	2 / 226 (0.88%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	2	1	0	0	0	0	0
Injection site swelling
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Mass
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Malaise
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Medical device site rash
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Oedema peripheral
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	2 / 226 (0.88%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	2	1	0	0	0	0	0
Pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Peripheral swelling
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Pyrexia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	2 / 242 (0.83%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	1	0	0	2	0	0	0	1	0
Swelling
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	2 / 238 (0.84%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0
Swelling face
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	2 / 238 (0.84%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0
Therapeutic response unexpected
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Xerosis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	2 / 238 (0.84%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	4	0	0	0	0	0	0	0
Immune system disorders
Allergy to chemicals
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	0	0	1	0	0	0	0	1
Food allergy
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Hypersensitivity
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Seasonal allergy
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Social circumstances
Victim of crime
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Reproductive system and breast disorders
Benign prostatic hyperplasia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Dysmenorrhoea
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	3	0	0	0	0	0	0	0
Erectile dysfunction
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Hypomenorrhoea
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Menorrhagia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Metrorrhagia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Ovarian cyst
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Ovarian disorder
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Balanoposthitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Prostatitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Asthma
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	2 / 238 (0.84%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	2	0	1	0	0	0	0	0
Cough
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	3 / 238 (1.26%)	4 / 226 (1.77%)	3 / 242 (1.24%)	0 / 60 (0.00%)	0 / 57 (0.00%)	3 / 217 (1.38%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	2	3	5	4	0	0	3	0	1
Dyspnoea
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Epistaxis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Nasal crusting
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0
Nasal dryness
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Oropharyngeal pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	1 / 238 (0.42%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	2	1	0	1	0	0	1	0	1
Pulmonary mass
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Rhinorrhoea
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	2	0	2	0	0	0	0	0	0
Sinus congestion
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Snoring
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Throat irritation
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Wheezing
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0
Sleep apnoea syndrome
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Psychiatric disorders
Anxiety
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	2 / 238 (0.84%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	2	0	1	0	0	0	0	0
Apathy
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Depression
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0
Depression suicidal
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Insomnia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	2	0	1	0	0	0	0	0	0
Irritability
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Libido decreased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Mood swings
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Schizophrenia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Hepatobiliary disorders
Gallbladder polyp
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Biliary colic
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Hepatic function abnormal
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Hepatic lesion
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Hyperbilirubinaemia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Liver disorder
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Investigations
Activated partial thromboplastin time prolonged
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Alanine aminotransferase increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	2 / 238 (0.84%)	1 / 226 (0.44%)	1 / 242 (0.41%)	1 / 60 (1.67%)	0 / 57 (0.00%)	0 / 217 (0.00%)	2 / 208 (0.96%)	0 / 223 (0.00%)
occurrences all number	1	2	1	1	1	0	0	3	0
Aspartate aminotransferase increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	2 / 238 (0.84%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	2	1	0	0	0	0	0	0
Biopsy endometrium
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Blood bilirubin increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Blood cholesterol increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	1 / 223 (0.45%)
occurrences all number	0	0	0	1	0	0	0	1	1
Blood creatine phosphokinase increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	3 / 131 (2.29%)	7 / 238 (2.94%)	6 / 226 (2.65%)	2 / 242 (0.83%)	1 / 60 (1.67%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	3	7	7	3	1	0	1	0	0
Blood creatinine increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0
Blood lactate dehydrogenase increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Body temperature increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	1	1	0
C-reactive protein increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Cardiac murmur
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Ejection fraction decreased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Electrocardiogram QT prolonged
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Electrocardiogram T wave amplitude increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0
Haematocrit decreased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Haemoglobin decreased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	3 / 226 (1.33%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	2 / 208 (0.96%)	0 / 223 (0.00%)
occurrences all number	0	0	3	1	0	0	0	2	0
Lipids increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Liver function test increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Natural killer cell count decreased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	2 / 238 (0.84%)	4 / 226 (1.77%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	2	4	0	0	0	0	1	0
Red blood cell count decreased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
T-lymphocyte count decreased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Transaminases increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Weight increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Blood pressure increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Blood urea increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Gamma-glutamyltransferase increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	1 / 60 (1.67%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0
Liver function test abnormal
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	1 / 57 (1.75%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Urine analysis abnormal
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Eosinophil percentage increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Animal bite
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0
Clavicle fracture
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Contusion
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0
Eye injury
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0
Fall
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Foot fracture
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Head injury
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Joint injury
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Ligament sprain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0
Limb injury
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0
Medication error
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Muscle strain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0
Procedural pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Road traffic accident
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	1 / 57 (1.75%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	2	0	0	0	0	1	0	0	0
Scapula fracture
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Skin abrasion
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	3 / 226 (1.33%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	3	0	0	0	0	0	0
Skin laceration
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	1 / 57 (1.75%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	1	0	0	0	1	0	0	0
Soft tissue injury
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Tooth fracture
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Traumatic haematoma
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Wound haemorrhage
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Arthropod bite
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Epicondylitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Humerus fracture
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	0	0	0	0	0	0	0	1
Thermal burn
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Wound
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	1 / 57 (1.75%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Congenital, familial and genetic disorders
Dermoid cyst
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Congenital lacrimal passage anomaly
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	0	0	0	0	0	0	0	1
Cardiac disorders
Arrhythmia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Atrioventricular block first degree
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Bradycardia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Defect conduction intraventricular
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	2	1	0	0	0	0	1	0	1
Palpitations
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Sinus bradycardia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	3 / 242 (1.24%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	3	0	0	0	0	0
Ventricular extrasystoles
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Nervous system disorders
Dizziness
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	4 / 238 (1.68%)	7 / 226 (3.10%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	2 / 217 (0.92%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	2	5	8	0	0	0	2	0	0
Dysaesthesia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
External compression headache
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Headache
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	6 / 131 (4.58%)	10 / 238 (4.20%)	15 / 226 (6.64%)	13 / 242 (5.37%)	1 / 60 (1.67%)	1 / 57 (1.75%)	2 / 217 (0.92%)	0 / 208 (0.00%)	2 / 223 (0.90%)
occurrences all number	9	12	17	14	1	1	3	0	2
Hypertonia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Hypoaesthesia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Migraine
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0
Nerve compression
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Neuralgia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Neuropathy peripheral
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Paraesthesia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0
Parosmia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Presyncope
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Somnolence
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	3 / 238 (1.26%)	2 / 226 (0.88%)	2 / 242 (0.83%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	3	2	2	0	0	0	0	0
Tension headache
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0
Leukopenia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	3 / 226 (1.33%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	3	0	0	0	0	0	0
Lymphadenitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Lymphadenopathy
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0
Lymphopenia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0
Microcytic anaemia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Thrombocytopenia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Thrombocytosis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	2 / 238 (0.84%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0
Ear and labyrinth disorders
External ear inflammation
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Vertigo positional
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Eye disorders
Asthenopia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Blepharitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Conjunctival haemorrhage
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Conjunctival irritation
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Conjunctivitis allergic
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	1 / 226 (0.44%)	2 / 242 (0.83%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	1	1	2	0	0	0	0	1
Dry eye
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	1	0	1	0	0	0	0	1
Eye irritation
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	2 / 242 (0.83%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0
Eye pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0
Eye pruritus
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	1 / 238 (0.42%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	1	1	1	0	0	0	0	0
Eyelid oedema
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	3 / 238 (1.26%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	3	1	0	0	0	0	0	0
Eyelid pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Eyelids pruritus
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Lacrimation increased
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0
Noninfective conjunctivitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Ocular discomfort
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Ocular hyperaemia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Presbyopia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Swelling of eyelid
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Vision blurred
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Eczema eyelids
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Eyelid cyst
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal discomfort
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	3 / 226 (1.33%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	3	0	0	0	0	0	0
Abdominal distension
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	1	0	1	1	0	0	0	0	1
Abdominal pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	3 / 226 (1.33%)	3 / 242 (1.24%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	5	3	0	0	0	0	0
Abdominal pain upper
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	2	0	0	0	1	0	0
Anal pruritus
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Constipation
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Dental caries
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	2 / 226 (0.88%)	0 / 242 (0.00%)	1 / 60 (1.67%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	2	0	1	0	0	0	0
Diarrhoea
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	4 / 131 (3.05%)	4 / 238 (1.68%)	4 / 226 (1.77%)	3 / 242 (1.24%)	0 / 60 (0.00%)	2 / 57 (3.51%)	3 / 217 (1.38%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	4	5	4	3	0	2	3	1	0
Dyspepsia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	2 / 238 (0.84%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	2	1	0	0	0	0	1	0
Faeces soft
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Flatulence
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Food poisoning
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Frequent bowel movements
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Gastritis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
Gastrooesophageal reflux disease
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	2 / 238 (0.84%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0
Gingival pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Inguinal hernia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Nausea
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	10 / 238 (4.20%)	25 / 226 (11.06%)	7 / 242 (2.89%)	0 / 60 (0.00%)	5 / 57 (8.77%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	2	12	29	8	0	6	0	0	0
Noninfective gingivitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Tooth impacted
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Toothache
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	1 / 238 (0.42%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	1	1	1	0	0	0	0	0
Vomiting
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	1 / 238 (0.42%)	3 / 226 (1.33%)	4 / 242 (1.65%)	0 / 60 (0.00%)	0 / 57 (0.00%)	2 / 217 (0.92%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	1	4	4	0	0	2	0	0
Gastritis erosive
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	0	0	0	0	0	0	0	1
Skin and subcutaneous tissue disorders
Acne
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	7 / 238 (2.94%)	15 / 226 (6.64%)	3 / 242 (1.24%)	1 / 60 (1.67%)	0 / 57 (0.00%)	2 / 217 (0.92%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	7	15	3	1	0	2	0	0
Actinic keratosis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Alopecia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Alopecia areata
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Angioedema
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Blister
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0
Dermatitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	2 / 238 (0.84%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	2	1	0	0	0	0	0	0
Dermatitis allergic
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Dermatitis atopic
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	4 / 131 (3.05%)	7 / 238 (2.94%)	3 / 226 (1.33%)	2 / 242 (0.83%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	4 / 208 (1.92%)	2 / 223 (0.90%)
occurrences all number	6	8	3	2	0	0	1	4	2
Drug eruption
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Dyshidrotic eczema
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Eczema
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Erythema
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Hyperhidrosis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Hyperkeratosis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0
Ingrowing nail
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Intertrigo
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Keratosis pilaris
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Nail bed disorder
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Nail fold inflammation
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Neurodermatitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Neutrophilic dermatosis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Photosensitivity reaction
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Pruritus
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	3 / 238 (1.26%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	2 / 217 (0.92%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	6	0	1	0	0	2	0	0
Pruritus allergic
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Rash
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	2 / 238 (0.84%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	3	2	0	0	0	0	0	0
Rash erythematous
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Rash papular
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	2 / 208 (0.96%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Seborrhoea
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0
Seborrhoeic dermatitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	2 / 208 (0.96%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Skin discolouration
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Skin disorder
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0
Skin fissures
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0
Skin lesion
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	2	0	0	0	0	0	0
Urticaria
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	3 / 238 (1.26%)	1 / 226 (0.44%)	1 / 242 (0.41%)	1 / 60 (1.67%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	3	3	1	0	0	0	1	0
Dermatitis contact
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Renal and urinary disorders
Acute kidney injury
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Dysuria
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Pollakiuria
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Polyuria
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Calculus urinary
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Haematuria
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Leukocyturia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Urinary tract inflammation
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	2 / 226 (0.88%)	2 / 242 (0.83%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	2	2	0	0	0	0	0
Arthritis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Arthropathy
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Back pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	5 / 131 (3.82%)	0 / 238 (0.00%)	1 / 226 (0.44%)	7 / 242 (2.89%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	5	0	1	7	0	0	1	0	1
Bursitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	1	0	1	0	0	0	0	0	0
Foot deformity
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Mandibular mass
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Muscle spasms
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Muscle tightness
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Musculoskeletal pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	2	0	0	1	0	0	0	0	0
Musculoskeletal stiffness
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Osteoarthritis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Pain in extremity
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0
Plantar fasciitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Rotator cuff syndrome
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Spinal pain
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Synovitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Temporomandibular joint syndrome
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Tendonitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Joint swelling
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Intervertebral disc protrusion
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	0	0	0	0	0	0	0	1
Infections and infestations
Abscess limb
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Bacterial vaginosis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0
Body tinea
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	1 / 238 (0.42%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	1	0	1	0	0	0	0	0
Bronchitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	1 / 238 (0.42%)	1 / 226 (0.44%)	0 / 242 (0.00%)	1 / 60 (1.67%)	0 / 57 (0.00%)	0 / 217 (0.00%)	2 / 208 (0.96%)	0 / 223 (0.00%)
occurrences all number	1	1	1	0	1	0	0	2	0
Cellulitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	2 / 217 (0.92%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	2	0	0	0	2	0	0
Conjunctivitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	3 / 131 (2.29%)	2 / 238 (0.84%)	3 / 226 (1.33%)	15 / 242 (6.20%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	2 / 223 (0.90%)
occurrences all number	4	2	3	16	0	0	0	0	2
Conjunctivitis bacterial
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Cystitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Dermatophytosis of nail
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Ear infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Eczema herpeticum
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0
Eczema infected
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Epstein-Barr virus infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Erysipelas
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Folliculitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	4 / 131 (3.05%)	4 / 238 (1.68%)	4 / 226 (1.77%)	2 / 242 (0.83%)	0 / 60 (0.00%)	1 / 57 (1.75%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	4	4	4	2	0	1	0	1	0
Fungal infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Fungal skin infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Furuncle
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	1 / 60 (1.67%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	2	1	0	0	1	0	0	0	0
Gastroenteritis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	2 / 226 (0.88%)	3 / 242 (1.24%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	2	3	0	0	1	0	0
Gastroenteritis viral
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	0	0	1	0	0	0	0	1
Gastrointestinal infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Gingivitis
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Hand-foot-and-mouth disease
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Herpes dermatitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Herpes simplex
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	5 / 238 (2.10%)	8 / 226 (3.54%)	2 / 242 (0.83%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	4 / 208 (1.92%)	1 / 223 (0.45%)
occurrences all number	1	5	8	2	0	0	1	4	1
Herpes virus infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Herpes zoster
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	4 / 226 (1.77%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	1	4	0	0	0	0	1	0
Hordeolum
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	2 / 238 (0.84%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	2	1	0	0	0	1	0	0
Impetigo
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	5 / 238 (2.10%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	5	0	0	0	0	1	0	0
Influenza
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	1 / 60 (1.67%)	0 / 57 (0.00%)	2 / 217 (0.92%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	1	1	0	2	0	0
Kaposi's varicelliform eruption
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Laryngitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Lower respiratory tract infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Malassezia infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Molluscum contagiosum
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Nasopharyngitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	9 / 131 (6.87%)	22 / 238 (9.24%)	15 / 226 (6.64%)	23 / 242 (9.50%)	3 / 60 (5.00%)	2 / 57 (3.51%)	3 / 217 (1.38%)	9 / 208 (4.33%)	5 / 223 (2.24%)
occurrences all number	12	24	16	24	3	2	3	9	5
Ophthalmic herpes simplex
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	2	0	0	0	0	0	0
Ophthalmic herpes zoster
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	0	1	0	0	0	0	0	0	0
Oral herpes
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	3 / 238 (1.26%)	2 / 226 (0.88%)	5 / 242 (2.07%)	0 / 60 (0.00%)	1 / 57 (1.75%)	0 / 217 (0.00%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	1	3	2	6	0	1	0	0	1
Otitis media
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Paronychia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	1	1	0	0	1	0	0
Perichondritis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Pharyngitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	2 / 238 (0.84%)	1 / 226 (0.44%)	2 / 242 (0.83%)	1 / 60 (1.67%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	2	1	2	1	0	0	0	0
Pharyngitis bacterial
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Pharyngotonsillitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Pulpitis dental
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Pustule
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Rash pustular
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Respiratory tract infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	2 / 238 (0.84%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	2	2	0	1	0	0	1	1	0
Respiratory tract infection viral
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Rhinitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	2 / 226 (0.88%)	3 / 242 (1.24%)	0 / 60 (0.00%)	0 / 57 (0.00%)	2 / 217 (0.92%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	3	3	0	0	2	0	0
Sinusitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	1 / 238 (0.42%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	1 / 57 (1.75%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	1	1	0	1	0	1	0	1	0
Sinusitis bacterial
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Skin bacterial infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Skin candida
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Skin infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	1 / 238 (0.42%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	1	1	0	0	0	0	0	0
Staphylococcal skin infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Subcutaneous abscess
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Tinea pedis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	1 / 131 (0.76%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Tinea versicolour
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	1 / 57 (1.75%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0
Tonsillitis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	1	1	0	0	1	0	0
Tooth abscess
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	2 / 242 (0.83%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0
Tooth infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0
Upper respiratory tract infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	6 / 131 (4.58%)	12 / 238 (5.04%)	9 / 226 (3.98%)	9 / 242 (3.72%)	1 / 60 (1.67%)	0 / 57 (0.00%)	6 / 217 (2.76%)	5 / 208 (2.40%)	7 / 223 (3.14%)
occurrences all number	6	13	10	9	1	0	6	5	8
Ureaplasma infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Urinary tract infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	2 / 131 (1.53%)	4 / 238 (1.68%)	7 / 226 (3.10%)	4 / 242 (1.65%)	2 / 60 (3.33%)	0 / 57 (0.00%)	2 / 217 (0.92%)	0 / 208 (0.00%)	1 / 223 (0.45%)
occurrences all number	2	5	8	4	2	0	2	0	1
Urinary tract infection bacterial
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	2 / 242 (0.83%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0
Viral infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Viral upper respiratory tract infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	2 / 238 (0.84%)	2 / 226 (0.88%)	0 / 242 (0.00%)	0 / 60 (0.00%)	1 / 57 (1.75%)	2 / 217 (0.92%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	2	2	0	0	1	2	0	0
Vulvovaginal mycotic infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
Wound infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Asymptomatic bacteriuria
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Bronchitis bacterial
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	1 / 57 (1.75%)	0 / 217 (0.00%)	1 / 208 (0.48%)	1 / 223 (0.45%)
occurrences all number	0	0	0	0	0	1	0	1	1
Bronchitis viral
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	1 / 208 (0.48%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Gastrointestinal viral infection
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	1 / 60 (1.67%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0
Genital herpes simplex
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Nasal herpes
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	1 / 60 (1.67%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Pneumonia bacterial
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Vulvovaginal candidiasis
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Metabolism and nutrition disorders
Decreased appetite
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Dyslipidaemia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Hypercholesterolaemia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Hyperglycaemia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Hypertriglyceridaemia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	1 / 242 (0.41%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Hypophosphataemia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Increased appetite
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Obesity
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	1 / 226 (0.44%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	1 / 217 (0.46%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
Type 2 diabetes mellitus
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	1 / 238 (0.42%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	0 / 208 (0.00%)	0 / 223 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Hyperuricaemia
Additional description: MedDRA v22.1 was used for coding events till Week 16 and MedDRA v23.0 was used for coding events post Week 16.
subjects affected / exposed	0 / 131 (0.00%)	0 / 238 (0.00%)	0 / 226 (0.00%)	0 / 242 (0.00%)	0 / 60 (0.00%)	0 / 57 (0.00%)	0 / 217 (0.00%)	2 / 208 (0.96%)	0 / 223 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0

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Were there any global substantial amendments to the protocol? Yes

29 May 2019

A clarification to the criteria for screening ECG findings has been added ,as the intent is that the subject’s screening ECG must not have clinically significant adverse findings.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and a Reduction of Greater Than or Equal to (>=) 2 Points From Baseline at Week 12

Primary: Percentage of Subjects Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and a Reduction of Greater Than or Equal to (>=) 2 Points From Baseline at Week 12

Primary: Percentage of Subjects Achieving Eczema Area and Severity Index (EASI) Response >=75 Percent (%) Improvement From Baseline at Week 12

Primary: Percentage of Subjects Achieving Eczema Area and Severity Index (EASI) Response >=75 Percent (%) Improvement From Baseline at Week 12

Secondary: Percentage of Subjects With at Least 4 Points Improvement in the Numerical Rating Scale (NRS) for Severity of Pruritus From Baseline at Day 2-15, Week 2, 4, 8, 12 and 16

Secondary: Percentage of Subjects With at Least 4 Points Improvement in the Numerical Rating Scale (NRS) for Severity of Pruritus From Baseline at Day 2-15, Week 2, 4, 8, 12 and 16

Secondary: Percentage of Subjects Achieving IGA Response of Clear (0) or Almost Clear (1) and a Reduction of >=2 Points From Baseline at Week 2, 4, 8 and 16

Secondary: Percentage of Subjects Achieving IGA Response of Clear (0) or Almost Clear (1) and a Reduction of >=2 Points From Baseline at Week 2, 4, 8 and 16

Secondary: Percentage of Subjects Achieving EASI Response >=75% Improvement From Baseline at Week 2, 4, 8 and 16

Secondary: Percentage of Subjects Achieving EASI Response >=75% Improvement From Baseline at Week 2, 4, 8 and 16

Secondary: Percentage of Subjects Achieving EASI Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16

Secondary: Percentage of Subjects Achieving EASI Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16

Secondary: Percentage of Subjects Achieving EASI Response >=90% Improvement From Baseline at Week 2, 4, 8, 12 and 16

Secondary: Percentage of Subjects Achieving EASI Response >=90% Improvement From Baseline at Week 2, 4, 8, 12 and 16

Secondary: Percentage of Subjects Achieving EASI Response =100% Improvement From Baseline at Week 2, 4, 8, 12 and 16

Secondary: Percentage of Subjects Achieving EASI Response =100% Improvement From Baseline at Week 2, 4, 8, 12 and 16

Secondary: Time From Baseline to First Achieve at Least 4 Points Improvement in the Severity of Pruritus NRS

Secondary: Time From Baseline to First Achieve at Least 4 Points Improvement in the Severity of Pruritus NRS

Secondary: Change From Baseline in Percentage Body Surface Area (BSA) at Week 2, 4, 8, 12 and 16

Secondary: Change From Baseline in Percentage Body Surface Area (BSA) at Week 2, 4, 8, 12 and 16

Secondary: Percentage BSA at Week 18 and 20

Secondary: Percentage BSA at Week 18 and 20

Secondary: Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8, 12 and 16

Secondary: Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8, 12 and 16

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 12 and 16

Secondary: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 12 and 16

Secondary: DLQI at Week 20

Secondary: DLQI at Week 20

Secondary: Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Index Value at Week 12 and 16

Secondary: Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Index Value at Week 12 and 16

Secondary: Change From Baseline in EQ-5D-5L Visual Analogue Scale (VAS) Score at Week 12 and 16

Secondary: Change From Baseline in EQ-5D-5L Visual Analogue Scale (VAS) Score at Week 12 and 16

Secondary: EQ-5D-5L- Index Value at Week 20

Secondary: EQ-5D-5L- Index Value at Week 20

Secondary: EQ-5D-5L- VAS Score at Week 20

Secondary: EQ-5D-5L- VAS Score at Week 20

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) – Anxiety Scale at Week 12 and 16

Secondary: Change From Baseline in Hospital Anxiety and Depression Scale (HADS) – Anxiety Scale at Week 12 and 16

Secondary: Change From Baseline in HADS – Depression Scale at Week 12 and 16

Secondary: Change From Baseline in HADS – Depression Scale at Week 12 and 16

Secondary: HADS – Anxiety Scale at Week 20

Secondary: HADS – Anxiety Scale at Week 20

Secondary: HADS – Depression Scale at Week 20

Secondary: HADS – Depression Scale at Week 20

Secondary: Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 12 and 16

Secondary: Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 12 and 16

Secondary: POEM at Week 20

Secondary: POEM at Week 20

Secondary: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score Week 1 to Week 16

Secondary: Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score Week 1 to Week 16

Secondary: PSAAD Total Score at Week 18 and 20

Secondary: PSAAD Total Score at Week 18 and 20

Secondary: Percentage of Subjects With Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16

Secondary: Percentage of Subjects With Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16

Secondary: Percentage of Subjects With SCORAD Response >=75% Improvement From Baseline at Week 2, 4, 8 12 and 16

Secondary: Percentage of Subjects With SCORAD Response >=75% Improvement From Baseline at Week 2, 4, 8 12 and 16

Secondary: Change From Baseline in SCORAD Visual Analogue Scale (VAS) of Itch and Sleep Loss at Week 2, 4, 8 12 and 16

Secondary: Change From Baseline in SCORAD Visual Analogue Scale (VAS) of Itch and Sleep Loss at Week 2, 4, 8 12 and 16

Secondary: SCORAD VAS of Itch and Sleep Loss at Week 18 and 20

Secondary: SCORAD VAS of Itch and Sleep Loss at Week 18 and 20

Secondary: Least Square Mean of Number of Steroid-free Days From Baseline up to Week 16

Secondary: Least Square Mean of Number of Steroid-free Days From Baseline up to Week 16

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information